Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.

Background: In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS). Methods: All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older. Results: A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n = 1,006; 41.8%) and unspecified MM (n = 792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations. Conclusions: Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.

Mortality from silicosis in Brazil: Temporal trends in the period 1980-2017.

BACKGROUND: Silicosis is the most prevalent pneumoconiosis in Brazil. We aimed to estimate mortality rates and temporal trends for silicosis, and to identify areas of highest mortality. METHODS: Records of silicosis as the underlying (1980-2017) or contributory (2000-2017) cause of death in adults aged 20 years and older were retrieved from the Brazilian Mortality Database. Age-standardized mortality rates (ASMR) were calculated. The annual trend in ASMR was analyzed by joinpoint regression. Mortality rates per 100,000 person-years were calculated for each municipality. We analyzed temporal trends in municipalities where similar activities with exposure to silica were performed. RESULTS: There were 3164 death records (96.6% men) distributed over 14% of the municipalities. Mean age of death was 59.2 (SD 15.1) and mean ASMR was 0.085/100,000 (confidence interval 0.080-0.091). Joinpoint regression showed a significant increase in ASMR from 1980 to 2006 and a significant decrease after 2006 driven by a decline in deaths of individuals younger than 70 years. The highest mortality rate was 21.83/100,000 person-years, in a municipality with small mining operations for gems. Gold mining municipalities showed the highest composite death rate, 4.0/100,000 person-years. Tuberculosis was the main cause of death when silicosis was a contributing cause. CONCLUSIONS: In contrast with developed countries, silicosis mortality in Brazil increased to 2006 and subsequently started to drop, mostly from a plateau or decrease in deaths occurring in municipalities which regulated economic activities. However, this decrease did not occur in the older age group nor in the unregulated sector, the latter being the main challenge for exposure control and surveillance.

Alouatta trichromatic color vision: cone spectra and physiological responses studied with microspectrophotometry and single unit retinal electrophysiology.

The howler monkeys (Alouatta sp.) are the only New World primates to exhibit routine trichromacy. Both males and females have three cone photopigments. However, in contrast to Old World monkeys, Alouatta has a locus control region upstream of each opsin gene on the X-chromosome and this might influence the retinal organization underlying its color vision. Post-mortem microspectrophotometry (MSP) was performed on the retinae of two male Alouatta to obtain rod and cone spectral sensitivities. The MSP data were consistent with only a single opsin being expressed in each cone and electrophysiological data were consistent with this primate expressing full trichromacy. To study the physiological organization of the retina underlying Alouatta trichromacy, we recorded from retinal ganglion cells of the same animals used for MSP measurements with a variety of achromatic and chromatic stimulus protocols. We found MC cells and PC cells in the Alouatta retina with similar properties to those previously found in the retina of other trichromatic primates. MC cells showed strong phasic responses to luminance changes and little response to chromatic pulses. PC cells showed strong tonic response to chromatic changes and small tonic response to luminance changes. Responses to other stimulus protocols (flicker photometry; changing the relative phase of red and green modulated lights; temporal modulation transfer functions) were also similar to those recorded in other trichromatic primates. MC cells also showed a pronounced frequency double response to chromatic modulation, and with luminance modulation response saturation accompanied by a phase advance between 10-20 Hz, characteristic of a contrast gain mechanism. This indicates a very similar retinal organization to Old-World monkeys. Cone-specific opsin expression in the presence of a locus control region for each opsin may call into question the hypothesis that this region exclusively controls opsin expression.

Contrast sensitivity of pattern transient VEP components: contribution from M and P pathways

The purpose of this study was to compare contrast sensitivity estimated from transient visual evoked potentials (VEPs) elicited by achromatic pattern-reversal and pattern-onset/offset modes. The stimuli were 2-cpd, achromatic horizontal gratings presented either as a 1 Hz pattern reversal or a 300 ms onset/700 ms offset stimulus. Contrast thresholds were estimated by linear regression to amplitudes of VEP components vs. the logarithm of the stimulus contrasts, and these regressions were extrapolated to the zero amplitude level. Contrast sensitivity was defined as the inverse of contrast threshold. For pattern reversal, the relation between the P100 amplitude and log of the stimulus contrast was best described by two separate linear regressions. For the N135 component, a single straight line was sufficient. In the case of pattern onset/offset for both the C1 and C2 components, single straight lines described their amplitude vs. log contrast relations in the medium-to-low contrast range. Some saturation was observed for C2 components. The contrast sensitivity estimated from the low-contrast limb of the P100, from the N135, and from the C2 were all similar but higher than those obtained from the high-contrast limb of the P100 and C1 data, which were also similar to each other. With 2 cpd stimuli, a mechanism possibly driven by the M pathway appeared to contribute to the P100 component at medium-to-low contrasts and to the N135 and C2 components at all contrast levels, whereas another mechanism, possibly driven by the P and M pathways, appeared to contribute to the P100 component at high contrast and C1 component at all contrast levels...

Contrast sensitivity of pattern transient VEP components: contribution from M and P pathways

The purpose of this study was to compare contrast sensitivity estimated from transient visual evoked potentials (VEPs) elicited by achromatic pattern-reversal and pattern-onset/offset modes. The stimuli were 2-cpd, achromatic horizontal gratings presented either as a 1 Hz pattern reversal or a 300 ms onset/700 ms offset stimulus. Contrast thresholds were estimated by linear regression to amplitudes of VEP components vs. the logarithm of the stimulus contrasts, and these regressions were extrapolated to the zero amplitude level. Contrast sensitivity was defined as the inverse of contrast threshold. For pattern reversal, the relation between the P100 amplitude and log of the stimulus contrast was best described by two separate linear regressions. For the N135 component, a single straight line was sufficient. In the case of pattern onset/offset for both the C1 and C2 components, single straight lines described their amplitude vs. log contrast relations in the medium-to-low contrast range. Some saturation was observed for C2 components. The contrast sensitivity estimated from the low-contrast limb of the P100, from the N135, and from the C2 were all similar but higher than those obtained from the high-contrast limb of the P100 and C1 data, which were also similar to each other. With 2 cpd stimuli, a mechanism possibly driven by the M pathway appeared to contribute to the P100 component at medium-to-low contrasts and to the N135 and C2 components at all contrast levels, whereas another mechanism, possibly driven by the P and M pathways, appeared to contribute to the P100 component at high contrast and C1 component at all contrast levels.(AU)

The topography of cone photoreceptors in the retina of a diurnal rodent, the agouti (Dasyprocta aguti).

The presence, density distribution, and mosaic regularity of cone types were studied in the retina of the diurnal agouti, Dasyprocta aguti. Longwave-sensitive (L-) and shortwave-sensitive (S-) cones were detected by antibodies against the respective cone opsins. L- and S-cones were found to represent around 90 and 10% of the cone population, respectively. There was no evidence for L- and S-opsin coexpression in agouti cones. L-cone densities were highest, up to 14,000/mm2, along a horizontal visual streak located about 2-3 mm dorsal to the optic nerve, and the L-cone distribution showed a dorsoventral asymmetry with higher densities in ventral (about 10,000/mm2) than in dorsal (about 4000/mm2) retinal regions. This L-cone topography parallels the agouti's ganglion cell topography. S-cones had a peak density of 1500-2000/mm2 in the central retinal region but did not form a visual streak. Their distribution also showed a dorsoventral asymmetry with densities around 600/mm2 in dorsal and around 1000/mm2 in ventral retinal regions. The patterning of cone arrays was assessed by the density recovery profile analysis. At all eccentricities evaluated, the S-cone mosaic less efficiently packed than the L-cone mosaic. Rod densities ranged from 47,000/mm2 in peripheral to 64,000/mm2 in central retina, and rod:cone ratios were 4:1-9:1. The comparatively low rod density and high cone proportion appear well adapted to the diurnal lifestyle of the agouti.

Color discrimination ellipses of trichromats measured with transient and steady state visual evoked potentials.

The purpose of this work is to investigate the use of different forms of visual evoked potentials (VEPs) to measure color discrimination thresholds and to plot color discrimination ellipses (MacAdam, 1942). Five normal trichromats (24.5 +/- 2.6 years-old) were monocularly tested. Stimuli consisted of sinusoidal isoluminant chromatic gratings made from chromaticity pairs located along four different color directions radiating from one reference point of the CIE 1976 chromaticity diagram (u' = 0.225; v' = 0.415). Heterochromatic flicker photometry (HFP) was used to obtain the isoluminance condition for every subject and for all chromaticity pairs. VEPs were elicited using two cycles per degree grating stimuli at three different temporal configurations: transient, onset (300 ms)/offset (700 ms), 1 Hz fundamental frequency; steady-state, onset (50 ms)/offset (50 ms), 10 Hz fundamental frequency; and steady-state pattern reversal at 5 Hz fundamental frequency (10 Hz phase reversal). VEP amplitude was measured using transient VEP N1-P1 components and steady state VEP first (10 Hz) and second (20 Hz) harmonics. VEP amplitude was plotted as a function of chromatic distance in the CIE 1976 color space and the data points were extrapolated to zero amplitude level to obtain chromatic discrimination thresholds. The results were compared with psychophysical measurements performed using the same stimulus configurations and with the pseudoisochromatic method of Mollon-Reffin (one-way ANOVA). For all subjects and all stimulation methods, the ellipses showed small sizes, low ellipticities, and were vertically oriented. Despite some consistent differences in the results obtained with different procedures, there was no statistical difference between ellipses obtained electrophysiologically and psychophysically. For steady state VEPs, ellipses obtained from second harmonic amplitudes were larger and more elongated in the tritan direction than those obtained with first harmonic amplitudes.

Amplitude of the transient visual evoked potential (tVEP) as a function of achromatic and chromatic contrast: contribution of different visual pathways.

We investigated how the stimulation mode influences transient visual evoked potentials (tVEP) amplitude as a function of contrast of achromatic and isoluminant chromatic gratings. The chromatic stimulation probed only responses to the red-green axis. Visual stimuli were monocularly presented in a 5 degrees diameter circle, achromatic and chromatic horizontal gratings, 1 Hz pattern reversal stimulation, and achromatic and chromatic gratings, 300 ms onset per 700 ms offset stimulation. For the achromatic pattern reversal stimulation, a double slope function describes how the P100 amplitude varied as a function of log contrast which had a limb at low-to-medium contrasts and another limb at high contrasts. For the achromatic onset/offset stimulation, C2 amplitude saturated at the highest contrast tested and a single straight line described how it changed along most of the contrast range. Both presentation modes for chromatic gratings resulted in amplitude versus log contrast relations which were well described by single straight lines along most of the contrast range. The results may be interpreted as if at 2 cpd, achromatic pattern reversal stimulation evoked the activity of at least two visual pathways with high and low contrast sensitivity, respectively, while achromatic onset/offset stimulation favored the activity of a pathway with high contrast sensitivity. The neural activity in the M pathway is the best candidate to be the high contrast mechanism detected with pattern reversal and pattern onset/offset VEPs. The activity of color opponent pathways such as the P and K pathways either combined or in isolation seems to be responsible for VEPs obtained with isoluminant chromatic gratings at both presentation modes. When the amplitudes of chromatic VEPs were plotted in the same contrast scale as used for achromatic VEPs, chromatic contrast thresholds had similar values to those of the achromatic mechanism with high contrast sensitivity.

Mercury toxicity in Amazon gold miners: visual dysfunction assessed by retinal and cortical electrophysiology.

Amazonian gold mining activity results in human exposure to mercury vapor. We evaluated the visual system of two Amazonian gold miners (29 and 37 years old) by recording the transient pattern electroretinogram (tPERG) and transient pattern visual evoked potential (tPVEP). We compared these results with those obtained from a regional group of control subjects. For both tPERG and tPVEP, checkerboards with 0.5 or 2 cycles per degree (cpd) of spatial frequency were presented in a 16 degrees squared area, 100% Michelson contrast, 50cd/m2 mean luminance, and 1 Hz square-wave pattern-reversal presentation. Two averaged waveforms (n=240 sweeps, 1s each) were monocularly obtained for each subject in each condition. Both eyes were monocularly tested only in gold miners. Normative data were calculated using a final pooled waveform with 480 sweeps. The first gold miner, LCS, had normal tPERG responses. The second one, RNP, showed low tPERG (P50 component) amplitudes at 0.5 cpd for both eyes, outside the normative data, and absence of response at 2 cpd for his right eye. Delayed tPVEP responses (P100 component) were found at 2 cpd for LCS but the implicit times were inside the normative data. Subject RNP also showed delayed tPVEP responses (all components), but only the implicit time obtained with his right eye was outside the normative data at 2 cpd. We conclude that mercury exposure levels found in the Amazon gold miners is high enough to damage the visual system and can be assessed by non-invasive electrophysiological techniques.

Spatial luminance contrast sensitivity measured with transient VEP: comparison with psychophysics and evidence of multiple mechanisms.

PURPOSE: To compare the spatial luminance contrast sensitivity function (CSF) obtained with transient visual evoked potentials (VEPs) with that obtained with psychophysical measurements. METHODS: The stimuli consisted of horizontal luminance gratings. In the VEP experiments, 0.4, 0.8, 2, 4, 8, and 10 cpd of spatial frequency were used, at 1 Hz square-wave contrast-reversal mode. Eight to 10 Michelson contrasts were used at each spatial frequency. Contrast thresholds were estimated from extrapolation of contrast response functions. Psychophysical sensitivities were obtained with spatial gratings of 0.4, 0.8, 1, 2, 4, 6, 8, and 10 cpd and presented at 1 Hz square-wave contrast-reversal or stationary mode (dynamic and static presentation, respectively). CSF tuning was estimated by calculating the ratio between peak sensitivity and the sensitivity at 0.4 cpd. RESULTS: In all subjects tested (n = 6), VEP contrast-response functions showed nonlinearities-namely, amplitude saturation and double-slope amplitude functions that occurred at low and medium-to-high spatial frequencies, respectively. Mean electrophysiological and psychophysical CSFs peaked at 2 cpd. CSF tuning for electrophysiology and dynamic and static psychophysics were, respectively, 1.08, 1.11, and 1.31. Correlation coefficients (r(2)) between electrophysiological CSF and dynamic or static psychophysical CSF were, respectively, 0.81 and 0.45. CONCLUSIONS: Electrophysiological and psychophysical CSFs correlated more positively when temporal presentation was similar. Spatial frequencies higher than 2 cpd showed that at least two visual pathways sum their activities at high contrasts. At low contrast levels, the results suggest that the transient VEP is dominated by the magnocellular (M) pathway.

Normal and dichromatic color discrimination measured with transient visual evoked potential.

It would be informative to have an electrophysiological method to study, in an objective way, the effects of mercury exposure and other neurotoxics on human color vision performance. The purpose of the present work was to study human color discrimination by measuring chromatic difference thresholds with visual evoked potential (VEP). Six young normal trichromats (24 +/- 1 years old) and one deutan (26 years old) were tested. The stimuli consisted of sinusoidal isoluminant chromatic gratings made from chromaticity pairs located along four different color directions centered on two reference points. Heterochromatic flicker photometry (HFP) protocol was used to obtain the isoluminance condition for every subject and for all chromaticity pairs. Spatial frequency was 2 cycles/deg. Presentation mode comprised onset (300 ms)/offset (700 ms) periods. As previously described, we found a negative deflection in the VEP which was related to the chromatic difference: as chromatic difference increased, amplitude increased and latency decreased. VEP response amplitude was plotted against distance in the CIE 1976 color space between the grating chromaticities and fitted with a regression line. We found color thresholds by extrapolating the fitting to null amplitude values. The thresholds were plotted in the CIE 1976 color space as MacAdam ellipses. In normal trichromats the ellipses had small size, low ellipticity, and were vertically oriented. In the deutan subject, the ellipses had large size, high ellipticity, and were oriented towards the deutan copunctal locus. The VEP thresholds were similar to those obtained using grating stimuli and psychophysical procedures, however smaller than those obtained using pseudoisochromatic stimuli (Mollon-Reffin method). We concluded that transient VEP amplitude as a function of contrast can be reliably used in objective studies of chromatic discrimination performance in normal and altered human subjects.

Visual impairment on dentists related to occupational mercury exposure.

A detailed assessment of visual function was obtained in subjects with low-level occupational mercury exposure by measuring hue saturation thresholds and contrast sensitivity functions for luminance and chromatic modulation. General practice dentists (n=15) were compared to age-matched healthy controls (n=13). Color discrimination estimated by the area of Mac Adam ellipses was impaired, showing diffuse discrimination loss. There was also reduction of contrast sensitivity for luminance and chromatic (red-green and blue-yellow) modulation, in all tested spatial frequencies. Low concentrations of urinary mercury (1.97±1.61µg/g creatinine) were found in the dentists group. Color discrimination as well as contrast sensitivity function, assessed psychophysically, constitutes a sensitive indicator of subtle neurotoxic effect of elemental mercury exposure.

Morphology and physiology of primate M- and P-cells.

Catarrhines and platyrrhines, the so-called Old- and New-World anthropoids, have different cone photopigments. Postreceptoral mechanisms must have co-evolved with the receptors to provide trichromatic color vision, and so it is important to compare postreceptoral processes in these two primate groups, both from anatomical and physiological perspectives. The morphology of ganglion cells has been studied in the retina of catarrhines such as the diurnal and trichromatic Macaca, as well as platyrrhines such as the diurnal, di- or trichromatic Cebus, and the nocturnal, monochromatic Aotus. Diurnal platyrrhines, both di- and trichromats, have ganglion cell classes very similar to those found in catarrhines: M (parasol), P (midget), small-field bistratified, and several classes of wide-field ganglion cells. In the fovea of all diurnal anthropoids, P-cell dendritic trees contact single midget bipolars, which contact single cones. The Aotus retina has far fewer cones than diurnal species, but M- and P-cells are similar to those in diurnal primates although of larger size. As in diurnal anthropoids, in the Aotus, the majority of midget bipolar cells, found in the central 2 mm of eccentricity, receive input from a single cone and the sizes of their axon terminals match the sizes of P-cell dendritic fields in the same region. The visual responses of retinal ganglion cells of these species have been studied using single-unit electrophysiological recordings. Recordings from retinal ganglion cells in Cebus and Aotus showed that they have very similar properties as those in the macaque, except that P-cells of mono- and dichromatic animals lack cone opponency. Whatever the original role of the M- and P-cells was, they are likely to have evolved prior to the divergence of catarrhines and platyrrhines. M- and P-cell systems thus appear to be strongly conserved in the various primate species. The reasons for this may lie in the roles of these systems for both achromatic and chromatic vision.

Morphology of horizontal cells in the retina of the capuchin monkey, Cebus apella: how many horizontal cell classes are found in dichromatic primates?

The morphology of horizontal cells was studied in the retina of dichromatic capuchin monkeys, Cebus apella. The cells were labeled with the carbocyanine dye, 1,1',dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), and the labeling was then photoconverted to a stable product by using a diaminobenzidine reaction. The sizes of cell body, dendritic field, and axon terminal, as well as the number of dendritic clusters and cone convergence, were measured at increasing distance from the fovea. Three distinct morphological classes of horizontal cells were identified. Their dendritic and axonal morphology resembles those of H1, H2, and H3 cells described in trichromatic primates. The size of the cell bodies, dendritic fields, and axon terminals of all cell classes increases towards retinal periphery. H3 cells have larger dendritic fields and more dendritic clusters than H1 cells. All labeled horizontal cells located in selected patches of retina were further analyzed to quantify the differences between H1 and H3 cells. H1 cells have smaller dendritic field area, smaller total length of primary dendrites, more dendritic branching points, and larger fractal dimension than H3 cells. We have distinguished H1 and H3 cells based solely in morphological criteria. Their physiology should be further analyzed with detail, but their presence in both dichromatic and trichromatic primates suggests that neither of them have a specialized role in the red-green color opponent channel of color vision.