Abstract Objective : To examine whether exposures or activities in farming, forestry and related occupations explain the excess incidence of germ cell cancer (GCC) observed among male employees in ...one of the six car-manufacturing plants that is located in a geographic area where farming is frequent. Methods : A cohort based case–control study was conducted among workers in six car-manufacturing plants located in areas with different industrial structure. The study involved 188 cases of germ cell cancer identified through active retrieval in 38 hospitals and 1000 controls, drawn from administrative accounting files, individually matched by year of birth (±2 years). Information regarding tasks and exposures and potential confounding variables were obtained by face-to-face or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a conditional logistic regression model adjusted for cryptorchidism and other potential confounders. Results : In this case–control study 5.3% of cases and 6.3% of controls ever worked in agriculture or livestock farming. No increased risks were observed for working in agriculture (OR = 0.8 95% CI: 0.4–1.6), livestock farming (OR = 0.8 95% CI: 0.4–1.6) or for exposure to pesticides (OR = 0.7 95% CI: 0.3–1.7), for exposure to fertilizers (OR = 0.8 95% CI: 0.4–1.8) and disinfectants (OR = 1.0 95% CI: 0.3–2.8). There were no statistically significant increases in risk associated with ever exposure to salt based wood protection agents (OR = 2.3 95% CI: 0.6–9.1), working with plywood (OR = 1.4 95% CI: 0.6–3.2), coated wood (OR = 1.4 95% CI: 0.5–3.9) or working in forestry (OR = 1.7 95% CI: 0.5–6.4). Lagging of exposures did not alter the results. Conclusions : The observed excess incidence in the cohort of automotive workers can be hardly explained by previous or concurrent work in farming or forestry. Because of the small numbers of subjects ever employed in farming the statistical power in assessing associations between agricultural work and agricultural exposures was limited and does not allow final conclusions about the association of farming related exposures and GCC risk.
Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for ...designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development. This channel is ideal for studying fluid shear stress applied to cells using microfluidic devices. We have developed an approach that allows us to analyze the role of Piezo channels on any given cell and serves as a high-throughput screen for drug discovery. We show that this approach can provide detailed information about the inhibitors of Piezo channels.
Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of ...depression associated with the condition.
618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with
ClinicalTrials.gov with the identifier NCT00111449.
47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0·0001; difference 42%, 95% CI 36–48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5·0
vs 1·9; p<0·0001, difference 3·0, 95% CI 1·6–4·5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain.
Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.
Prediabetes: prediction and prevention trials Vendrame, Francesco; Gottlieb, Peter A
Endocrinology and metabolism clinics of North America,
03/2004, Letnik:
33, Številka:
1
Journal Article
Some species belonging to the genera Galactia, Camptosema and Collaea from southern Brazil, Paraguay, Argentina, and Uruguay are grouped into a complex based on exomorphological affinities. The ...diagnostic morphological features sometimes overlap among species of different genera and dissimilar criteria have been adopted to delimit them, thus generating great taxonomic uncertainty. The aim of this work was to clarify the genetic relationships of the species within the complex as well as to analyze the infraspecific variability by means of analysing the AFLP band patterns. We examined 378 AFLP markers generated after amplification using six primer combinations. The monophyly of Collaea was supported, corroborating the present morphological classification. On the other hand, the results are not congruent with the current circumscription of Galactia and Camptosema, in agreement with previous phylogenetic hypotheses based on morphological characters and karyological studies, as both genera are polyphyletic.
Complex I deficiency is difficult to treat because of the size and complexity of the multi-subunit enzyme complex. Mutations or deletions in the mitochondrial genome are not amenable to gene therapy. ...However, animal studies have shown that yeast-derived internal NADH quinone oxidoreductase (Ndi1) can be delivered as a cell-permeable recombinant protein (Tat-Ndi1) that can functionally replace complex I damaged by ischemia/reperfusion. Current and future treatment of disorders affecting complex I are discussed, including the use of Tat-Ndi1.
Summary
Context Autoantibodies to 21‐hydroxylase (21OH‐AA) precede onset of autoimmune Addison’s disease (AD). Progression to AD can take months to years, and early detection of metabolic ...decompensation may prevent morbidity and mortality.
Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH‐AA+ individuals.
Design, Setting and Participants Individuals were screened for 21OH‐AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH‐AA (n = 87) were tested, and the majority prospectively followed for the development of Addison’s disease, including seven diagnosed with AD upon 21OH‐AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors.
Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH‐AA were measured at various time points relative to diagnosis of AD or last AD‐free follow‐up.
Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E‐4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH‐AA levels (P < 1E‐4) and poststimulation cortisol levels (P = 6E‐3).
Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH‐AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD.
Several groups have reported that during apoptosis, cytochrome c is released from the mitochondria into the cytosol, but we have found that in apoptotic cells the cytochrome appears to remain with ...the mitochondria. In hopes of reconciling these findings, we compared the results obtained from cells disrupted by our method (nitrogen cavitation) with those obtained using the cell-disruption method employed by others (homogenization). We observed that at 2 h, cytochrome c levels in apoptotic cytosols from homogenized cells exceeded control levels, whereas cytochrome c levels in apoptotic cytosols fromcavitated cells were similar to control. Outer membranes of homogenized mitochondria appeared damaged because the mitochondria had become permeable to cytochrome c, whereas outer membranes of cavitated mitochondria excluded the cytochrome. 4 h after Fas ligation, both cavitated and homogenized mitochondria had released small amounts of cytochrome c into the cytosol, whereas after 6 h the cytochrome had disappeared from the cell lysate. We believe that the differences between our results and those reported by others were due to 1) our examining the cells after a short (2 h) incubation with the anti-Fas antibody, and 2) our use of nitrogen cavitation instead of homogenization to disrupt the cells.
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