Occupational Exposure to Solar Radiation and the Eye: A Call to Implement Health Surveillance of Outdoor Workers.

Globally, hundreds of millions of outdoor workers are exposed to solar radiation (SR) for the majority of their working life. Such occupational exposure is known to induce various adverse health effects to the eyes, mainly related to its ultraviolet (UV) component. The present work is a call-to-action aimed at raising the awareness on the need of health surveillance for the prevention of the chronic ocular diseases in outdoor workers. Photo-chemical chronic damage can induce pterygium at the outer layer of the eye and cataract in the lens. Considering carcinogenic effects, rare squamous-cells tumors of the cornea and/or of the conjunctiva and the ocular melanomas are associated with UV radiation exposure. Solar UV-related eye diseases should be considered as "occupational diseases" when there is sufficient exposure in workers, but they are often not recognized, and/or frequently not reported to the national compensation authorities. Therefore, to prevent the burden of these work-related eye pathologies, an adequate risk assessment with identification of appropriate preventive measures, and a provision of periodic health surveillance to the exposed workers, in particular considering those at higher risk of exposure or with individual susceptibility, should be urgently implemented.

Profiled polyethylene terephthalate filaments that incorporate collagen and calcium phosphate enhance ligamentisation and bone formation.

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.

A magneto-microfluidic platform for fluorescence immunosensing using quantum dot nanoparticles.

This study reports the online fluorescent detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) biomarker proteins in microfluidic channels using functional nanoparticles. Functional magnetic nanoparticles labeled with two antibodies were predeposited on separated microfluidic channels. Antigens were passed through each microfluidic channel to react with the respective antibodies. Two types of fluorescent nanoparticles labeled with antibodies were then used to detect and confirm antigens in the immunocomplex. Results indicate that online fluorescent detection of proteins can provide advantages for real-time monitoring and diagnostic applications. The running time was less than 20 min for each trial. The detection limits of CEA and AFP were found to be 0.6 and 0.2 pg ml-1. These detection limits are lower than those of ELISA. The linear ranges of CEA and AFP detection were from 1.8 pg ml-1 to 1.8 ng ml-1 and from 0.68 pg ml-1 to 0.68 ng ml-1 for two deposition zones in a magnetic sandwich immunoassay. The linear ranges of this method are wider than those of ELISA and those of most other methods. The measurements of CEA and AFP in serum samples from this method differed from ELISA results by 11% and 9.4%, respectively. The detection limit of online detection has achieved the same range as those of previous offline detection. This method has a good potential for automation and multichannel analysis to increase the throughput with some modifications in the future. The proposed method can provide simple, fast, and sensitive online detection for biomarkers.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to solar ultraviolet radiation and of the effect of occupational exposure to solar ultraviolet radiation on cataract.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. Here, we present the protocol for two systematic reviews of parameters for estimating the number of disability-adjusted life years of cataracts from occupational exposure to solar ultraviolet radiation, to inform the development of the WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on occupational exposure to solar ultraviolet radiation (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to solar ultraviolet radiation on the development of cataract (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework and conducting both systematic reviews in tandem and in a harmonized way. DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and Web of Sciences. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) workers in WHO and/or ILO Member States, but exclude children (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative studies on the prevalence of relevant levels of occupational exposure to solar ultraviolet radiation and of the total working time spent outdoors from 1960 to 2018, stratified by sex, age, country and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of any occupational exposure to solar ultraviolet radiation (i.e. ≥30 Jm-2/day of occupational solar UV exposure at the surface of the eye) on the prevalence or incidence of cataract, compared with the theoretical minimum risk exposure level (i.e. <30 Jm-2/day of occupational solar UV exposure at the surface of the eye). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration: CRD42018098897.

When is protection from impact needed for the face as well as the eyes in occupational environments?

BACKGROUND: The most commonly identified reason for requiring or using occupational eye and face protection is for protection against flying objects. Standards vary on what risk may require protection of the eyes alone and what requires protection for the whole face. Information on the minimum energy transfer for face damage to occur is not well-established. METHODS: The heads of pigs were used as the common model for human skin. A 6 mm steel ball projected at velocities between 45 and 135 m/s was directed at the face area. Examples of impacts were filmed with a high-speed camera and the resulting damage was rated visually on a scale from 1 (no visible damage) to 5 (penetrated the skin and embedded in the flesh). RESULTS: The results for the cheek area indicate that 85 m/s is the velocity above which damage is more likely to occur unless the skin near the lip is included. For damage to the lip area to be avoided, the velocity needs to be 60 m/s or less. CONCLUSION: The present data support a maximum impact velocity of 85 m/s, provided the thinner and more vulnerable skin of the lids and orbital adnexa is protected. If the coverage area does not extend to the orbital adnexa, then the absolute upper limit for the velocity is 60 m/s. At this stage, eye-only protection, as represented by the lowest level of impact test in the standards in the form of a drop ball test, is not in question.

Demographic and mortality analysis of hospitalized children at a referral hospital in Addis Ababa, Ethiopia.

BACKGROUND: Global childhood mortality rates remain high. Millennium Development Goal 4 focused efforts on reducing rates by two-thirds between 1990 and 2015. In Ethiopia, child mortality rates dropped 71 % from 1990 to 2015, however it is estimated that 184,000 Ethiopian children die each year. There is limited information about pediatric hospital admissions in Ethiopia. Our aims were to examine the temporal relationship of mortality to admission, describe the demographics, and identify cause mortality of children admitted to the Zewditu Memorial Hospital (ZMH). METHODS: A four-year retrospective review of pediatric admissions was conducted at the pediatric emergency room and pediatric hospital ward at ZMH in Addis Ababa, Ethiopia. Admission entries from 2011-2014 of children age 29 days-14 years were reviewed. Age, gender, admission date, disease classification, discharge status and date were obtained. Patient gender was compared using Chi-square analysis. A descriptive analysis was used for age and cause mortality. RESULTS: A total of 6866 patient entries were reviewed. The proportion of admissions younger than age 5 was 0.747 (95 % CI 0.736-0.757). Overall mortality was 0.042 (95 % CI, 0.037-0.047). The proportion of recorded deaths occurring within 2 days of admission was 0.437 (95 % CI 0.380-0.494). The proportion of male admissions was significantly higher than female admissions in all age groups (male 0.575, p < 0.0001, 95 % CI 0.562-0.586). The main causes of mortality were pneumonia (0.253, 95 % CI, 0.203-0.303), severe acute malnutrition (0.222, 95 % CI 0.174-0.27), HIV/AIDS-related complications (0.056, 95 % CI 0.029-0.083), spina bifida (0.049, 95 % CI 0.024-0.074), and hydrocephalus (0.045, 95 % CI 0.021-0.069). CONCLUSIONS: Our study revealed a lower mortality rate than previously reported in Ethiopia. Despite this, 44 % of pediatric hospital mortality occurred early during hospitalization, higher than reported at other Ethiopian hospitals. This adds further evidence that systematic efforts should be dedicated to improve pediatric emergency care. Admissions included 58 % male patients, similar to other reports in Ethiopia implying that this may be a nation-wide phenomenon. The observed disparity may be due to societal factors regarding care-seeking behaviors or male predilection for respiratory illness warranting further investigation. Cause mortality patterns were similar to reports in analogous settings.

Effect of Ultraviolet Exposure on Impact Resistance of Ophthalmic Lenses.

PURPOSE: To investigate the effect of ultraviolet radiation (UVR) on the impact resistance of organic ophthalmic lens materials. METHODS: Plano power CR39, Phoenix, Trilogy, and polycarbonate lenses with various scratch-resistant (SR) and/or antireflection (AR) coatings were obtained in batches of 40 units. All lenses had a nominal thickness of 2 mm. Half of each batch was conditioned following the European Standard EN 168 protocol for the test of resistance to UVR (exposed group). The remaining lenses comprised an unexposed group for that combination of lens substrate and coating treatment. Each group was subjected to ballistic impact with 6-mm steel balls following the ZEST protocol to determine its mean breakage velocity. The difference in mean breakage velocity between exposed and unexposed groups of each combination of lens substrate and coating was assessed for statistical significance. RESULTS: Exposed uncoated CR39 showed a reduction in fracture velocity of 10.3 m/s whereas CR39 with ultra hard coat had a reduction of 3.5 m/s and CR39 with AR and SR coating had a reduction of 4.1 m/s. Scratch-resistant coated Phoenix had a reduction of 4.8 m/s whereas AR-coated Phoenix had a reduction of 3.7 m/s. The corresponding reductions for Trilogy were 3.9 and 17.8 m/s. All differences were significant at the p level of less than 0.05. Although we were unable to break unexposed SR-coated polycarbonate lenses with our test apparatus, exposed SR-coated polycarbonate had a mean breakage velocity of 142 m/s. CONCLUSIONS: Our data suggest that extended UVR exposure causes a significant reduction in the impact resistance of the ophthalmic lens substrates commonly used for occupational eye protectors. Protective lenses that have been exposed to high levels of UVR for extended periods should be replaced regularly to maintain optimal impact protection, even if they do not show visible damage owing to wear and tear.

Forward light scatter and visual acuity through scratched protective eyewear.

BACKGROUND: Scratches and other surface abrasions on protective eyewear can shorten their life cycle by scattering light from the image, which will compromise visual performance. Although scratch and abrasion resistance testing is well developed, there is little information available regarding visual acuity through lenses scratched in an actual work environment. METHODS: We collected protective eyewear from mine and smelting operations that had been returned because vision through the lenses was unacceptable due to scratches and abrasions. Forward scattered light was measured on both cleaned and partially cleaned lenses using both haze and light diffusion measurements. Visual acuity through a selection of lenses was determined for both high and low contrast letters under photopic light levels. RESULTS: Lenses with scratches in the central region had haze values ranging from one to 30 per cent. The highest haze values were measured on lenses that were both scratched and covered with dirt, whereas haze values less than 10 per cent were measured on lenses that had the dirt removed and just had scratches in the central region. Light diffusion values were highly correlated with haze. Visual acuity for high and low contrast letters became worse as the percentage haze increased but the linear correlation was only moderate. CONCLUSION: The appearance of the scratches on the lens surfaces strongly suggests that they were a result of improper lens cleaning. The findings also suggest that haze values less than two per cent or a luminance reduction factor less than 3.0 cd/(m(2) lx) are unlikely to affect high and low contrast acuity.

Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1ß and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.

Ballistic impact resistance of selected organic ophthalmic lenses.

PURPOSE: The aim was to assess the impact resistance of coated and uncoated mid-index spectacle lens materials using the ballistic impact test. METHODS: Nominally plano lenses of each material in three thicknesses were obtained. The lenses were flat edged to a 50 mm diameter. Each lens was impacted by a 6.35 mm steel ball. Impact velocities were selected using the Zippy Estimation by Sequential Testing protocol to determine the threshold fracture impact velocity. RESULTS: Threshold fracture impact velocity generally increased with thickness; however, there was a wide variation in performance among the various lens materials at each thickness. In all but two instances, the differences in impact velocity at each thickness of lens material were significant. Comparison of the data for CR39 and Hoya Phoenix with the results of earlier studies showed that the lens mounting is a significant factor. The fracture velocities found in the present study were significantly lower than the fracture velocities found when the lens edge is restrained in the mounting. A scratch resistant coating reduced the impact resistance of CR39. The effect of the antireflection coating on the fracture velocity depended on the nature of the base scratch-resistant coating. CONCLUSIONS: Mid-index lens materials of the same thickness show widely varying levels of impact resistance under the ballistic test. Impact resistance increases non-linearly with centre thickness. The lens mounting might affect the results of the ballistic impact test. The presence of 'cushion coatings' might enhance impact resistance.

Prescription compliance in ophthalmic lenses.

PURPOSE: Tolerances required for ophthalmic lenses are set down in national and international standards. It appears that the compliance of manufactured lenses has not been reported previously. Assembling a statistical quantity of lenses of a single prescription is usually an expensive process. It was, secondary to a lens impact study, possible to assemble a large number of plano lenses. In the assessment of the fracture velocity of lenses approximately 20 plano lenses of each material and thickness are required. Prior to using lenses for the impact study, they were checked for prescription. The results of the prescription measurements are reported here and the results of the impact study are reported in a separate paper. METHODS: Using an automated focimeter, 679 plano lenses in stock thickness, typical occupational eye protector thickness and up to 3.5 mm thick were measured. There were 21 combinations of material/thickness/coating from seven suppliers. The power was evaluated against Australian Standard 2228.1-1992, as the lenses were supplied in Australia. The permitted tolerances are ±0.09 D sphere and ±0.06 D cylinder. RESULTS: When assessed for material/thickness/coating combination, failure rates varied from <0.0001 per cent to 77.5 per cent (with a further 17.3 per cent classified as borderline, because they were within the uncertainty of measurement of the required limit). Grouped by supplier, the failure rates ranged from <0.0001 per cent to 7.6 per cent (with a further 12.3 per cent borderline). To improve understanding of the result, it may be easier to quote the figures without considering uncertainties. When assessed by supplier, the failure rate varies from <0.0001 per cent to 12.6 per cent. CONCLUSIONS: Compliance of plano lenses should be among the easiest of tasks for a laboratory. While we know of no defined or required acceptance rates for prescription lenses, a failure rate for a laboratory of 12.6 per cent, which includes a failure rate of 88 per cent in 2.8 mm thick refractive index = 1.53 hard coated lenses (n = 20) cannot be considered satisfactory and is a strong indication of a failure to check lenses before they leave the laboratory.

Determination of GDC-0449, a small-molecule inhibitor of the Hedgehog signaling pathway, in human plasma by solid phase extraction-liquid chromatographic-tandem mass spectrometry.

To support clinical development, a solid phase extraction (SPE) liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the determination of GDC-0449 concentrations in human plasma has been developed and validated. Samples (200 microl) were extracted using an Oasis MCX 10 mg 96-well SPE plate and the resulting extracts were analyzed using reverse-phase chromatography coupled with a turbo-ionspray interface. The method was validated over calibration curve range 5-5000 ng/mL. Quadratic regression and 1/x(2) weighing were used. Within-run relative standard deviation (%RSD) was within 10.1% and accuracy ranged from 88.6% to 109.0% of nominal. Between-run %RSD was within 8.6% and accuracy ranged from 92.4% to 105.3% of nominal. Extraction recovery of GDC-0449 was between 88.3% and 91.2% as assessed using quality control sample concentrations. GDC-0449 was stable in plasma for 315 days when stored at -70 degrees C and stable in reconstituted sample extracts for 117 h when stored at room temperature. Quantitative matrix effect/ion suppression experiment was performed and no significant matrix ion suppression was observed. This assay allows for the determination of GDC-0449 plasma concentrations over a sufficient time period to determine pharmacokinetic parameters at relevant clinical doses.

Preclinical assessment of the absorption, distribution, metabolism and excretion of GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide), an orally bioavailable systemic Hedgehog signalling pathway inhibitor.

GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide) is a potent, selective Hedgehog (Hh) signalling pathway inhibitor being developed for the treatment of various cancers. The in vivo clearance of GDC-0449 was estimated to be 23.0, 4.65, 0.338, and 19.3 ml min(-1) kg(-1) in mouse, rat, dog and monkeys, respectively. The volume of distribution ranged from 0.490 in rats to 1.68 l kg(-1) in mice. Oral bioavailability ranged from 13% in monkeys to 53% in dogs. Predicted human clearance using allometry was 0.096-0.649 ml min(-1) kg(-1) and the predicted volume of distribution was 0.766 l kg(-1). Protein binding was extensive with an unbound fraction less than or equal to 6%, and the blood-to-plasma partition ratio ranged from 0.6 to 0.8 in all species tested. GDC-0449 was metabolically stable in mouse, rat, dog and human hepatocytes and had a more rapid turnover in monkey hepatocytes. Proposed metabolites from exploratory metabolite identification in vitro (rat, dog and human liver microsomes) and in vivo (dog and rat urine) include three primary oxidative metabolites (M1-M3) and three sequential glucuronides (M4-M6). Oxidative metabolites identified in microsomes M1 and M3 were formed primarily by P4503A4/5 (M1) and P4502C9 (M3). GDC-0449 was not a potent inhibitor of P4501A2, P4502B6, P4502D6, and P4503A4/5 with IC50 estimates greater than 20 microM. K(i)'s estimated for P4502C8, P4502C9 and P4502C19 and were 6.0, 5.4 and 24 microM, respectively. An evaluation with Simcyp suggests that GDC-0449 has a low potential of inhibiting P4502C8 and P4502C9. Furthermore, GDC-0449 (15 microM) was not a potent P-glycoprotein/ABCB1 inhibitor in MDR1-MDCK cells. Overall, GDC-0449 has an attractive preclinical profile and is currently in Phase II clinical trials.

Effects of 400 nm, 420 nm, and 435.8 nm radiations on cultured human retinal pigment epithelial cells.

The present study demonstrates narrowband short-wavelengths radiation- (400, 420, and 435.8 nm) induced cellular damage of cultured human retinal pigment epithelial cells using in vitro biological assays to determine wavelengths that are responsible for photochemical lesions of the retina. This work involved the exposure of retinal pigment epithelial (RPE) cells (ARPE-19) to narrowband light of three different wavelengths (400, 420, and 435.8 nm) using a xenon arc lamp and interference filters. Cellular viability, mitochondrial distribution, and nucleic acid (both DNA and RNA) damage were quantified after various energy levels of exposure, using the Alamar blue assay, and confocal laser scanning microscopy with two fluorescent stains (Rhodamine 123 and Acridine Orange). The results clearly show that 400 nm light radiation can cause significant dose-dependent decreases in RPE cell viability as well as degradations of DNA/RNA and mitochondria in RPE cells, while 420 and 435.8 nm light radiation cause no cellular damage. While further evaluations may be needed to assess specificity and confounding factors of these assessment tools, the results may be a matter for consideration in future IOL design efforts.

Effect of multiple antireflection coatings on impact resistance of Hoya Phoenix spectacle lenses.

PURPOSE: To investigate how the impact resistance of Hoya Phoenix spectacle lenses is affected by centre thickness and the application of a multilayer antireflection (MAR) coating. METHODS: Four groups of plano lenses were tested: dress thickness with scratch resistant (SR) coating on both surfaces, dress thickness with SR and MAR, industrial thickness with SR and industrial thickness with SR and MAR. Lenses were edged to a clear circular aperture of 50 mm with a 0.5 mm hidden bevel and mounted in a specially-designed lens support. A pneumatic gun was used to propel a 6.35 mm steel ball at the centre of each lens. Impact speed was varied using the ZEST protocol to determine the threshold breakage speed. RESULTS: The threshold breakage speeds of the dress and industrial thickness SR lenses were 55.1 and 63.2 m/s, respectively and the corresponding threshold breakage speeds for SR-MAR lenses were 50.1 and 54.7 m/s. All comparisons were statistically significant using Student's t-test with a rejection level of p < 0.005. Unlike polycarbonate lenses, dress thickness Phoenix lenses do not display 'oilcanning' deformation on high energy impact and therefore are less likely to be dislodged from their mountings. CONCLUSIONS: We found that the mean impact resistance of the Phoenix lenses was greater than the level required of eye protector lenses by the standards AS/NZS 1337:1992, ANSI Z87.1-2003 and CSA Z94.3-02. Similar to CR39 and polycarbonate, the application of MAR to Phoenix lenses reduces their impact resistance, however, they provide an acceptable level of impact protection in industrial settings, where there is little danger of exposure to pointed or sharp-edged high-speed missiles.

The effect of multiple antireflective coatings and center thickness on resistance of polycarbonate spectacle lenses to penetration by pointed missiles.

PURPOSE: Previous work has shown that the impact resistance to blunt missiles is affected by coatings applied to either CR-39 or polycarbonate lenses. We investigated the effects of multiple antireflection (minimum angle of resolution [MAR]) coatings on the resistance of polycarbonate lenses to puncture on impact by sharp, high-speed missiles. METHODS: Four groups of surfaced plano polycarbonate lenses were investigated. Two groups had a scratch-resistant (SR) coating applied to both surfaces. One of these groups had a 2-mm center thickness and the other had a 3-mm center thickness. The other two groups of 2-mm and 3-mm thick lenses had a MAR coating applied over the SR coating. The lenses were impacted by a missile consisting of an industrial sewing machine needle mounted in a cylindrical aluminum carrier. RESULTS: The sharp missiles were able to pierce the lenses at speeds between 29.6 m/s and 46.2 m/s. Impact resistance was lowest for the thinner lenses and lenses with a MAR coating. The effect of the MAR and lens thickness was subadditive. CONCLUSIONS: We have confirmed previous observations that polycarbonate lenses are more susceptible to penetration by sharp, high-speed missiles than blunt missiles. We have also found that reducing lens center thickness and applying a MAR coating further reduces the penetration resistance. Therefore, the use of 2-mm center thickness and MAR-coated polycarbonate lenses should be discouraged for industrial eye protectors where sharp missile hazards are possible.

A novel DNA vaccine based on ubiquitin-proteasome pathway targeting 'self'-antigens expressed in melanoma/melanocyte.

Cancer vaccine that targets 'self'-antigens expressed at high levels in tumor cells is a potentially useful immunotherapy, but immunological tolerance often defeats this strategy. Here, we describe the use of a naked DNA vaccine encoding a self tumor antigen, tyrosinase-related protein 2, to whose N-terminus ubiquitin is fused in a 'nonremovable' fashion. Unlike conventional DNA vaccines, this vaccine broke the tolerance and induced protective immunity to melanoma in C57BL/6 mice, as evaluated by tumor growth, survival rate and lung metastasis. The protective immunity was cancelled in the proteasome activator PA28alpha/beta knockout mice. Moreover, this vaccination exhibited therapeutic effects on melanoma implanted before vaccination. Our findings provide evidence for the first time that naked DNA vaccines encoding a ubiquitin-fused self-antigen preferentially induce the main effector CD8+ T cells through efficient proteolysis mediated by the ubiquitin-proteasome pathway, and lead the way to strategies aimed at targeting tissue differentiation antigens expressed by tumors.

Durability of coated CR-39 industrial lenses.

PURPOSE: To study the effect of coatings on the resistance of CR-39 industrial plano lenses to ballistic impacts and abrasion from fine particles. METHODS: Twelve groups of CR-39 lenses with various scratch-resistant (SR) or combinations of scratch-resistant and antireflective (SR-AR) coatings were mounted in metal industrial spectacle frames. The ZEST protocol was used to determine the mean impact speed for breakage of each lens group using the Canadian Standards Association ballistic test protocol. One pair of lenses from each group was tested for abrasion resistance using the falling sand method. Abrasion resistance was ranked by the degree of haze observed by three independent observers. RESULTS: Uncoated lenses had the best impact resistance and worst abrasion resistance. SR-coated lenses showed mild to moderate reductions in impact resistance, with no correlation between impact and abrasion resistance. SR-AR-coated lenses had very good abrasion resistance, but severely reduced impact resistance. CONCLUSIONS: Most SR-coated CR-39 lenses have a high probability of meeting the high-velocity impact resistance requirement of industrial lenses, whereas CR-39 lenses with SR-AR coats are too fragile to be used in industrial spectacles. As a group, the SR-AR coating tended to be more resistant to abrasion by fine particles and less resistant to ballistic impacts, but the abrasion resistance of the SR-coated lenses was more variable, and, thus, overall there was no significant correlation between impact resistance and abrasion resistance.

Carcinogenicity of inhaled vanadium pentoxide in F344/N rats and B6C3F1 mice.

Vanadium pentoxide (V2O5) is a slightly soluble compound found in airborne particle emissions from metallurgical works and oil and coal burning. Because the carcinogenic potential of V2O5 was not known, F344/N rats and B6C3F1 mice (N=50/sex/species) were exposed to V2O5 at concentrations of 0, 0.5 (rats only), 1, 2, or 4 (mice only) mg/m3, by whole-body inhalation for 2 years. The survival and body weights of rats were minimally affected by exposure to V2O5. The survival and body weights of male mice exposed to 4 mg/m3 and body weights of all exposed groups of female mice were lower than the controls. Alveolar/bronchiolar (A/B) neoplasms occurred in male rats exposed to 0.5 and 2 mg/m3 at incidences exceeding the National Toxicology Program (NTP) historical control ranges. A marginal increase in A/B neoplasms was also observed in female rats exposed to 0.5 mg/m3. Increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar hyperplasia/metaplasia and squamous metaplasia were observed in exposed male and female rats. A/B neoplasms were significantly increased in all groups of exposed mice. As with rats, increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar epithelial hyperplasia were observed in mice exposed to V2O5. Thus, V2O5 exposure was a pulmonary carcinogen in male rats and male and female mice. The marginal tumor response in the lungs of female rats could not be attributed conclusively to exposure to V2O5. These responses were noted at and slightly above the OSHA permissible occupational exposure limit of 0.5 mg/m3 (dust) (National Institute for Occupational Safety and Health, NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Washington, DC, 1997, p. 328).