Electrophysiological evidence for impairment of contrast sensitivity in mercury vapor occupational intoxication

Contrast sensitivity (CS) was evaluated in 41 former workers from a lamp manufacturing plant who were on disability retirement due to exposure to mercury and 14 age-matched controls. The CS was measured monocularly using the sweep visual evoked potential (sVEP) paradigm at 6 spatial frequencies (0.2, 0.8, 2.0, 4.0, 15.0, and 30 cpd). Statistical difference (p < 0.05) was found between the controls and the patient right and left eyes for 2.0 and 4.0 cpd. According the results in those spatial frequencies the eyes were classified in best and worst. Statistical differences were found between the controls and the best eyes for 2.0 and 4.0 cpd and for 0.8, 2.0, and 4.0 cpd for their worst eyes. No correlation was found between CS results and the time of exposure (mean 8.9 yr +/- 4.1), time away from the mercury source (mean = 6.0 yr +/- 3.9), urinary mercury level at the time of work (mean = 40.6 mu g/g +/-36.3) or with the mercury level at the CS measurement time (mean = 1.6 mu g/g +/-1.1). We show the first evidence of a permanent impairment in CS measured objectively with the sVEP. Our data complement the previous psychophysical works reporting a diffuse impairment in the CS function showing a CS reduction in the low to middle spatial frequencies. In conclusion, non-reversible CS impairment was found in occupational exposure to mercury vapor. We suggest that CS measurement should be included in studies of the mercury effects of occupational exposure. (C) 2007 Elsevier Inc. All rights reserved.

Contrast Sensitivity Mediated by Inferred Magno- and Parvocellular Pathways in Type 2 Diabetics with and without Nonproliferative Retinopathy

PURPOSE. To evaluate achromatic contrast sensitivity (CS) with magnocellular-(M) and parvocellular-(P) probing stimuli in type 2 diabetics, with (DR) or without (NDR) nonproliferative retinopathy. METHODS. Inferred M-and P-dominated responses were assessed with a modified version of the steady-/pulsed-pedestal paradigm (SP/PP) applied in 26 NDR (11 male; mean age, 55 +/- 9 years; disease duration, 5 +/- 4 years); 19 DR (6 male; mean age, 58 +/- 7 years; disease duration = 9 +/- 6 years); and 18 controls (CTRL; 12 male; mean age, 55 +/- 10 years). Thresholds were measured with pedestals at 7, 12, and 19 cd/m(2), and increment durations of 17 and 133 ms. The thresholds from the two stimulus durations were used to estimate critical durations (Tc) for each data set. RESULTS. Both DR and NDR patients had significant reduction in CS in both SP and PP paradigms in relation to CTRL (Kruskal-Wallis, P < 0.01). Patients` critical duration estimates for either paradigm were not significantly different from CTRL. CONCLUSIONS. The significant reduction of CS in both paradigms is consistent with losses of CS in both M and P pathways. The CS losses were not accompanied by losses in temporal processing speed in either diabetic group. Significant CS loss in the group without retinopathy reinforces the notion that neural changes associated with the cellular and functional visual loss may play an important role in the etiology of diabetic visual impairment. In addition, the results show that the SP/PP paradigm provides an additional tool for detection and characterization of the early functional damage due to diabetes. (Invest Ophthalmol Vis Sci. 2011; 52:1151-1155) DOI:10.1167/iovs.09-3705

Double-Stranded RNA-Activated Protein Kinase Is a Key Modulator of Insulin Sensitivity in Physiological Conditions and in Obesity in Mice

The molecular integration of nutrient-and pathogen-sensing pathways has become of great interest in understanding the mechanisms of insulin resistance in obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate molecule that may provide cross talk between inflammatory and metabolic signaling. The present study was performed to determine, first, the role of PKR in modulating insulin action and glucose metabolism in physiological situations, and second, the role of PKR in insulin resistance in obese mice. We used Pkr(-/-) and Pkr(+/+) mice to investigate the role of PKR in modulating insulin sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and adipose tissue in response to a high-fat diet. Our data show that in lean Pkr(-/-) mice, there is an improvement in insulin sensitivity, and in glucose tolerance, and a reduction in fasting blood glucose, probably related to a decrease in protein phosphatase 2A activity and a parallel increase in insulin-induced thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of obese mice and can induce insulin resistance by directly binding to and inducing insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly through modulation of c-Jun N-terminal kinase and inhibitor of kappa B kinase beta. Pkr(-/-) mice were protected from high-fat diet-induced insulin resistance and glucose intolerance and showed improved insulin signaling associated with a reduction in c-Jun N-terminal kinase and inhibitor of kappa B kinase beta phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin sensitivity under normal physiological conditions, probably by modulating protein phosphatase 2A activity and serine-threonine kinase phosphorylation, and certainly, this kinase may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity. (Endocrinology 153:5261-5274, 2012)

Evaluation of the Sensitivity of Freshwater Organisms Used in Toxicity Tests of Wastewater from Explosives Company

Explosives industries are a source of toxic discharge. The aim of this study was to compare organisms sensitivity (Daphnia similis, Danio rerio, Escherichia coli and Pseudomonas putida) in detecting acute toxicity in wastewater from two explosives, 2,4,6-TNT (TNT) and nitrocellulose. The samples were collected from an explosives company in the Paraiba Valley, So Paulo, Brazil. The effluents from TNT and nitrocellulose production were very toxic for tested organisms. Statistical tests indicated that D. similis and D. rerio were the most sensitive organisms for toxicity detection in effluents from 2,4,6-TNT and nitrocellulose production. The P. putida bacteria was the organism considered the least sensitive in indicating toxicity in effluents from nitrocellulose.

Sensitivity of Eisenia andrei (Annelida, Oligochaeta) to a commercial formulation of abamectin in avoidance tests with artificial substrate and natural soil under tropical conditions

Obtaining ecotoxicological data on pesticides in tropical regions is imperative for performing more realistic risk analysis, and avoidance tests have been proposed as a useful, fast and cost-effective tool. Therefore, the present study aimed to evaluate the avoidance behavior of Eisenia andrei to a formulated product, Vertimec(A (R)) 18 EC (a.i abamectin), in tests performed on a reference tropical artificial soil (TAS), to derive ecotoxicological data on tropical conditions, and a natural soil (NS), simulating crop field conditions. In TAS tests an adaptation of the substrate recommended by OECD and ISO protocols was used, with residues of coconut fiber as a source of organic matter. Concentrations of the pesticide on TAS test ranged from 0 to 7 mg abamectin/kg (dry weight-d.w.). In NS tests, earthworms were exposed to samples of soils sprayed in situ with: 0.9 L of Vertimec(A (R)) 18 EC/ha (RD); twice as much this dosage (2RD); and distilled water (Control), respectively, and to 2RD: control dilutions (12.5, 25, 50, 75%). All tests were performed under 25 +/- A 2A degrees C, to simulate tropical conditions, and a 12hL:12hD photoperiod. The organisms avoided contaminated TAS for an EC50,48h = 3.918 mg/kg soil d.w., LOEC = 1.75 mg/kg soil d.w. and NOEC = 0.85 mg/kg soil d.w. No significant avoidance response occurred for any NS test. Abamectin concentrations in NS were rather lower than EC50, 48h and LOEC determined in TAS tests. The results obtained contribute to overcome a lack of ecotoxicological data on pesticides under tropical conditions, but more tests with different soil invertebrates are needed to improve pesticides risk analysis.

Experimental evidence for the sensitivity of the air-shower radio signal to the longitudinal shower development

We observe a correlation between the slope of radio lateral distributions and the mean muon pseudorapidity of 59 individual cosmic-ray-air-shower events. The radio lateral distributions are measured with LOPES, a digital radio interferometer colocated with the multidetector-air-shower array KASCADE-Grande, which includes a muon-tracking detector. The result proves experimentally that radio measurements are sensitive to the longitudinal development of cosmic-ray air showers. This is one of the main prerequisites for using radio arrays for ultra-high-energy particle physics and astrophysics.

Long-Term Occupational Exposure to Organic Solvents Affects Color Vision, Contrast Sensitivity and Visual Fields

The purpose of this study was to evaluate the visual outcome of chronic occupational exposure to a mixture of organic solvents by measuring color discrimination, achromatic contrast sensitivity and visual fields in a group of gas station workers. We tested 25 workers (20 males) and 25 controls with no history of chronic exposure to solvents (10 males). All participants had normal ophthalmologic exams. Subjects had worked in gas stations on an average of 9.6 +/- 6.2 years. Color vision was evaluated with the Lanthony D15d and Cambridge Colour Test (CCT). Visual field assessment consisted of white-on-white 24-2 automatic perimetry (Humphrey II-750i). Contrast sensitivity was measured for sinusoidal gratings of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0 and 20.0 cycles per degree (cpd). Results from both groups were compared using the Mann-Whitney U test. The number of errors in the D15d was higher for workers relative to controls (p<0.01). Their CCT color discrimination thresholds were elevated compared to the control group along the protan, deutan and tritan confusion axes (p<0.01), and their ellipse area and ellipticity were higher (p<0.01). Genetic analysis of subjects with very elevated color discrimination thresholds excluded congenital causes for the visual losses. Automated perimetry thresholds showed elevation in the 9 degrees, 15 degrees and 21 degrees of eccentricity (p<0.01) and in MD and PSD indexes (p<0.01). Contrast sensitivity losses were found for all spatial frequencies measured (p<0.01) except for 0.5 cpd. Significant correlation was found between previous working years and deutan axis thresholds (rho = 0.59; p<0.05), indexes of the Lanthony D15d (rho = 0.52; p<0.05), perimetry results in the fovea (rho = -0.51; p<0.05) and at 3, 9 and 15 degrees of eccentricity (rho = -0.46; p<0.05). Extensive and diffuse visual changes were found, suggesting that specific occupational limits should be created.

Relation of Uric Acid to Serum Levels of High-Sensitivity C-Reactive Protein, Triglycerides, and High-Density Lipoprotein Cholesterol and to Hepatic Steatosis

Increased uric acid (UA) is strongly linked to cardiovascular disease. However, the independent role of UA is still debated because it is associated with several cardiovascular risk factors including obesity and metabolic syndrome. This study assessed the association of UA with increased high-sensitivity C-reactive protein (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the presence and absence of obesity and metabolic syndrome. We evaluated 3,518 employed subjects without clinical cardiovascular disease from November 2008 through July 2010. Prevalence of tis-CRP >= 3 mg/L was 19%, that of TG/HDL >= 3 was 44%, and that of hepatic steatosis was 43%. In multivariable logistic regression after adjusting for traditional cardiovascular risk factors and confounders, highest versus lowest UA quartile was associated with hs-CRP >= 3 mg/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL >= 3 (OR 3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22 to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association of UA with hs-CRP >= 3 mg/L became nonsignificant in analyses stratified by obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a graded increase in the odds of having 2 or 3 of these risk conditions and a successive decrease in the odds of having none. In conclusion, high UA levels were associated with increased TG/HDL and hepatic steatosis independently of metabolic syndrome and obesity and with increased hs-CRP independently of metabolic syndrome. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1787-1792)

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (beta = 1.416, P = 0.039) and body mass index (beta = 0.390, P < 0.001), and was also inversely associated with adiponectin (beta = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Parameter recovery for a skew-normal IRT model under a Bayesian approach: hierarchical framework, prior and kernel sensitivity and sample size

Item response theory (IRT) comprises a set of statistical models which are useful in many fields, especially when there is an interest in studying latent variables (or latent traits). Usually such latent traits are assumed to be random variables and a convenient distribution is assigned to them. A very common choice for such a distribution has been the standard normal. Recently, Azevedo et al. [Bayesian inference for a skew-normal IRT model under the centred parameterization, Comput. Stat. Data Anal. 55 (2011), pp. 353-365] proposed a skew-normal distribution under the centred parameterization (SNCP) as had been studied in [R. B. Arellano-Valle and A. Azzalini, The centred parametrization for the multivariate skew-normal distribution, J. Multivariate Anal. 99(7) (2008), pp. 1362-1382], to model the latent trait distribution. This approach allows one to represent any asymmetric behaviour concerning the latent trait distribution. Also, they developed a Metropolis-Hastings within the Gibbs sampling (MHWGS) algorithm based on the density of the SNCP. They showed that the algorithm recovers all parameters properly. Their results indicated that, in the presence of asymmetry, the proposed model and the estimation algorithm perform better than the usual model and estimation methods. Our main goal in this paper is to propose another type of MHWGS algorithm based on a stochastic representation (hierarchical structure) of the SNCP studied in [N. Henze, A probabilistic representation of the skew-normal distribution, Scand. J. Statist. 13 (1986), pp. 271-275]. Our algorithm has only one Metropolis-Hastings step, in opposition to the algorithm developed by Azevedo et al., which has two such steps. This not only makes the implementation easier but also reduces the number of proposal densities to be used, which can be a problem in the implementation of MHWGS algorithms, as can be seen in [R.J. Patz and B.W. Junker, A straightforward approach to Markov Chain Monte Carlo methods for item response models, J. Educ. Behav. Stat. 24(2) (1999), pp. 146-178; R. J. Patz and B. W. Junker, The applications and extensions of MCMC in IRT: Multiple item types, missing data, and rated responses, J. Educ. Behav. Stat. 24(4) (1999), pp. 342-366; A. Gelman, G.O. Roberts, and W.R. Gilks, Efficient Metropolis jumping rules, Bayesian Stat. 5 (1996), pp. 599-607]. Moreover, we consider a modified beta prior (which generalizes the one considered in [3]) and a Jeffreys prior for the asymmetry parameter. Furthermore, we study the sensitivity of such priors as well as the use of different kernel densities for this parameter. Finally, we assess the impact of the number of examinees, number of items and the asymmetry level on the parameter recovery. Results of the simulation study indicated that our approach performed equally as well as that in [3], in terms of parameter recovery, mainly using the Jeffreys prior. Also, they indicated that the asymmetry level has the highest impact on parameter recovery, even though it is relatively small. A real data analysis is considered jointly with the development of model fitting assessment tools. The results are compared with the ones obtained by Azevedo et al. The results indicate that using the hierarchical approach allows us to implement MCMC algorithms more easily, it facilitates diagnosis of the convergence and also it can be very useful to fit more complex skew IRT models.

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B-max (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7 +/- 2.8 vs.8.1 +/- 1.3) and Bmax (6.5 +/- 0.9 vs. 3.9 +/- 0.3) were higher in pemphigus than controls (p = 0.002). Considering the values above the 95th percentile of normal group as a cut-off (K-d > 24.9 nM and B-max > 8.1 fmol/mg protein), elevated K-d and B-max were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p = 0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p < 0.001) in both pemphigus and control groups. IL-6 and TNF alpha (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in controls and remained elevated in pemphigus (p < 0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

Purpose: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. Methods: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. Results: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001) but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean +/- standard deviation baseline central macular thickness (552 +/- 150 mu m) reduced significantly one month (322 +/- 127 mu m, P=0.0001) and three months (439 perpendicular to 179 mu m, P=0.01) after treatment. Conclusions: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

Low Sensitivity of NS1 Protein Tests Evidenced during a Dengue Type 2 Virus Outbreak in Santos, Brazil, in 2010

In 2010, a large outbreak of dengue occurred in Santos, Brazil. The detection of the NS1 antigen was used for diagnosis in addition to the detection of IgG, IgM, and RNA. A large number of NS1 false-negative results were obtained. A total of 379 RNA-positive samples were selected for thorough evaluation. NS1 was reactive in 37.7% of cases. Most of the cases were characterized as a secondary infection by dengue 2 virus. Sequencing of NS1 positive and negative isolates did not reveal any mutation that could justify the diagnostic failure. Use of existing NS1 tests in the Brazilian population may present a low negative predictive value, and they should be used with caution, preferentially after performing a validation with samples freshly obtained during the ongoing epidemic.

Birth weight, current body mass index, and insulin sensitivity and secretion in young adults in two Latin American populations

Background and aims: Although studies have shown association of birth weight (BW) and adult body mass index (BMI) with insulin sensitivity in adults, there is limited evidence that BW is associated with insulin secretion. We assessed the associations between BW and current BMI with insulin sensitivity and secretion in young Latin American adults. Methods and results: Two birth cohorts, one from Ribeirao Preto, Brazil, based on 1984 participants aged 23-25 years, and another from Limache, Chile, based on 965 participants aged 22-28 years were studied. Weight and height at birth, and current fasting plasma glucose and insulin levels were measured. Insulin sensitivity (HOMA%S) and secretion (HOMA%beta) were estimated using the Homeostatic Model Assessment (HOMA2). Multiple linear regression analyses were carried out to test the associations between BW and adult BMI z-scores on log HOMA%S and log HOMA%beta. BW z-score was associated with HOMA%S in the two populations and HOMA%beta in Ribeirao Preto when adult BMI z-score was included in the model. BW z-score was associated with decreasing insulin secretion even without adjusting for adult BMI, but only in Ribeirao Preto. BMI z-score was associated with low HOMA%S and high HOMA%beta. No interactions between BW and BMI z-scores on insulin sensitivity were shown. Conclusions: This study supports the finding that BW may affect insulin sensitivity and secretion in young adults. The effect size of BW on insulin status is small in comparison to current BMI. (C) 2010 Elsevier B.V. All rights reserved.

A simple method to measure critical angles for high-sensitivity differential refractometry

A total internal reflection-based differencial refractometer, capable of measuring the real and imaginary parts of the complex refractive index in real time, is presented. The device takes advantage of the phase difference acquired by s- and p-polarized light to generate an easily detectable minimum at the reflected profile. The method allows to sensitively measuring transparent and turbid liquid samples. (C)2012 Optical Society of America