Cytogenetic analysis of an exposed-referent study: perchloroethylene-exposed dry cleaners compared to unexposed laundry workers

<p>Abstract</p> <p>Background</p> <p>Significant numbers of people are exposed to tetrachloroethylene (perchloroethylene, PCE) every year, including workers in the dry cleaning industry. Adverse health effects have been associated with PCE exposure. However, investigations of possible cumulative cytogenetic damage resulting from PCE exposure are lacking.</p> <p>Methods</p> <p>Eighteen dry cleaning workers and 18 laundry workers (unexposed controls) provided a peripheral blood sample for cytogenetic analysis by whole chromosome painting. Pre-shift exhaled air on these same participants was collected and analyzed for PCE levels. The laundry workers were matched to the dry cleaners on race, age, and smoking status. The relationships between levels of cytological damage and exposures (including PCE levels in the shop and in workers' blood, packyears, cumulative alcohol consumption, and age) were compared with correlation coefficients and t-tests. Multiple linear regressions considered blood PCE, packyears, alcohol, and age.</p> <p>Results</p> <p>There were no significant differences between the PCE-exposed dry cleaners and the laundry workers for chromosome translocation frequencies, but PCE levels were significantly correlated with percentage of cells with acentric fragments (R²= 0.488, p < 0.026).</p> <p>Conclusions</p> <p>There does not appear to be a strong effect in these dry cleaning workers of PCE exposure on persistent chromosome damage as measured by translocations. However, the correlation between frequencies of acentric fragments and PCE exposure level suggests that recent exposures to PCE may induce transient genetic damage. More heavily exposed participants and a larger sample size will be needed to determine whether PCE exposure induces significant levels of persistent chromosome damage.</p

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Evoked potentials in the Atlantic cod following putatively innocuous and putatively noxious electrical stimulation: a minimally invasive approach

Aspects of peripheral and central nociception have previously been studied through recording of somatosensory evoked potentials (SEPs) to putative noxious stimuli in specific brain regions in a few freshwater fish species. In the present study, we describe a novel, minimally invasive method for recording SEPs from the central nervous system of the Atlantic cod (Gadus morhua). Cutaneous electric stimulation of the tail in 15 fish elicited SEPs at all stimulus intensities (2, 5, 10 and 20 mA) with quantitative properties corresponding to stimulus intensity. In contrast to previous fish studies, the methodological approach used in Atlantic cod in the current study uncovered a number of additional responses that could originate from multiple brain regions. Several of these responses were specific to stimulation at the highest stimulus intensities, possibly representing qualitative differences in central processing between somatosensory and nociceptive stimuli

What motivates senior clinicians to teach medical students?

BACKGROUND: This study was designed to assess the motivations of senior medical clinicians to teach medical students. This understanding could improve the recruitment and retention of important clinical teachers. METHODS: The study group was 101 senior medical clinicians registered on a teaching list for a medical school teaching hospital (The Canberra Hospital, ACT, Australia). Their motivations to teach medical students were assessed applying Q methodology. RESULTS: Of the 75 participants, 18 (24%) were female and 57 (76%) were male. The age distribution was as follows: 30–40 years = 16 participants (21.3%), 41–55 years = 46 participants (61.3%) and >55 years = 13 participants (17.3%). Most participants (n = 48, 64%) were staff specialists and 27 (36%) were visiting medical officers. Half of the participants were internists (n = 39, 52%), 12 (16%) were surgeons, and 24 (32%) were other sub-specialists. Of the 26 senior clinicians that did not participate, two were women; 15 were visiting medical officers and 11 were staff specialists; 16 were internists, 9 were surgeons and there was one other sub-specialist. The majority of these non-participating clinicians fell in the 41–55 year age group. The participating clinicians were moderately homogenous in their responses. Factor analysis produced 4 factors: one summarising positive motivations for teaching and three capturing impediments for teaching. The main factors influencing motivation to teach medical students were intrinsic issues such as altruism, intellectual satisfaction, personal skills and truth seeking. The reasons for not teaching included no strong involvement in course design, a heavy clinical load or feeling it was a waste of time. CONCLUSION: This study provides some insights into factors that may be utilised in the design of teaching programs that meet teacher motivations and ultimately enhance the effectiveness of the medical teaching workforce

Current quark mass dependence of nucleon magnetic moments and radii

A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Survival trends for small intestinal cancer in England and Wales, 1971–1990: national population-based study

This population-based study examines prognostic factors and survival trends among adults (15–99 years) diagnosed with small intestinal cancer in England and Wales during 1971–1990 and followed up to 1995. During this period, the 1- and 5-year age-standardised relative survival rates for small intestinal cancers combined were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients with advanced age and the most deprived patients had the poorest prognosis. For all small bowel tumours combined, the excess risk of death fell significantly by 6–9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR) 0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR fell by about 14% (95% CI 5–22%) every 4 years between 1979 and 1990, and a similar trend for jejunal tumours was of borderline significance. Further population-based investigations linking survival data to individual data on diagnostic methods and types of treatment are needed

A controlled trial of protein enrichment of meal replacements for weight reduction with retention of lean body mass

<p>Abstract</p> <p>Background</p> <p>While high protein diets have been shown to improve satiety and retention of lean body mass (LBM), this study was designed to determine effects of a protein-enriched meal replacement (MR) on weight loss and LBM retention by comparison to an isocaloric carbohydrate-enriched MR within customized diet plans utilizing MR to achieve high protein or standard protein intakes.</p> <p>Methods</p> <p>Single blind, placebo-controlled, randomized outpatient weight loss trial in 100 obese men and women comparing two isocaloric meal plans utilizing a standard MR to which was added supplementary protein or carbohydrate powder. MR was used twice daily (one meal, one snack). One additional meal was included in the meal plan designed to achieve individualized protein intakes of either 1) 2.2 g protein/kg of LBM per day [high protein diet (HP)] or 2) 1.1 g protein/kg LBM/day standard protein diet (SP). LBM was determined using bioelectrical impedance analysis (BIA). Body weight, body composition, and lipid profiles were measured at baseline and 12 weeks.</p> <p>Results</p> <p>Eighty-five subjects completed the study. Both HP and SP MR were well tolerated, with no adverse effects. There were no differences in weight loss at 12 weeks (-4.19 ± 0.5 kg for HP group and -3.72 ± 0.7 kg for SP group, p > 0.1). Subjects in the HP group lost significantly more fat weight than the SP group (HP = -1.65 ± 0.63 kg; SP = -0.64 ± 0.79 kg, P = 0.05) as estimated by BIA. There were no significant differences in lipids nor fasting blood glucose between groups, but within the HP group a significant decrease in cholesterol and LDL cholesterol was noted at 12 weeks. This was not seen in the SP group.</p> <p>Conclusion</p> <p>Higher protein MR within a higher protein diet resulted in similar overall weight loss as the standard protein MR plan over 12 weeks. However, there was significantly more fat loss in the HP group but no significant difference in lean body mass. In this trial, subject compliance with both the standard and protein-enriched MR strategy for weight loss may have obscured any effect of increased protein on weight loss demonstrated in prior weight loss studies using whole food diets.</p

Worth the ‘EEfRT’? The Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia

Background: Of the putative psychopathological endophenotypes in major depressive disorder (MDD), the anhedonic subtype is particularly well supported. Anhedonia is generally assumed to reflect aberrant motivation and reward responsivity. However, research has been limited by a lack of objective measures of reward motivation. We present the Effort-Expenditure for Rewards Task (EEfRT or ‘‘effort’’), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans. Using the EEfRT, we test the hypothesis that effort-based decision-making is related to trait anhedonia. Methods/Results: 61 undergraduate students participated in the experiment. Subjects completed self-report measures of mood and trait anhedonia, and completed the EEfRT. Across multiple analyses, we found a significant inverse relationship between anhedonia and willingness to expend effort for rewards. Conclusions: These findings suggest that anhedonia is specifically associated with decreased motivation for rewards, and provide initial validation for the EEfRT as a laboratory-based behavioral measure of reward motivation and effort-base