APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer's Disease and Aging.

The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

In vivo and in vitro toxicity of a stainless-steel aerosol generated during thermal spray coating.

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.

Review of the physicochemical properties and associated health effects of aerosols generated during thermal spray coating processes.

Thermal spray coating is a process that applies a molten metal product under pressure onto a surface. Although thermal spray processes have been used for decades, exposure to aerosols formed during thermal spray coating is an emerging risk. Reports indicate that high concentrations of aerosols composed of toxic metals (e.g. chromium) are generated in the workplace. A knowledge gap exists related to the physicochemical properties of thermal spray coating aerosols as well as any potential associated health effects. The objective of this manuscript was to review thermal spray coating and previous studies that have examined the aerosols produced from this process. A thermal spray coating generator and exposure system is also described that has recently been developed to further evaluate the physical and chemical properties of aerosols formed during thermal spray coating as well as to assess the possible health effects of this process in an effort to mitigate potential occupational health hazards related to the industry.

Investigation of particle transfer to sampler covers during the transportation of samples.

This study investigated the effects of particle transfer to the covers of aerosol samplers during transportation of wood dust and welding fume samples. Wood dust samples were collected in a sanding chamber using four sampler types: closed-face cassettes (CFC), CFC with Accu-CAP inserts, disposable inhalable samplers (DIS), and Institute of Occupational Medicine (IOM). Welding fumes were collected in a walk-in chamber using the same samplers, with Solu-Sert replacing Accu-CAP. The samples were divided into two groups, with one group transported by air and the other by land. They were returned in the same manner and analyzed gravimetrically for wood dust and chemically for welding fumes. For wood dust, IOM showed a significantly higher percentage of particles transferred to the covers compared with the other samplers regardless of the transportation mode (p < 0.0001; 64% by air and 15% by land), while other samplers showed less than or close to 10% (3.5-12%). When the percentages of particle transfer to the covers were compared between the air and land transportation, both IOM and CFC samples showed differences between modes of transportation, while others did not. For welding fumes, most samples (61% of samples for copper [Cu] and 76% of samples for manganese [Mn]) showed nondetectable amounts of the analyte on the covers. For all samplers, the particle transfer to the covers for both transportation modes ranged from 0.2-33% for Cu and less than 4.5% for Mn. Overall, this study confirms that particle transfer to sampler covers during transport highly depends upon the transportation mode and sampler type for wood dust, whereas particle transfer seems minimal for welding fumes. The findings of this study are based on two materials and limited sample sizes. Further investigation considering different industry types and tasks, particle size ranges, and materials might be necessary. Nevertheless, occupational professionals should account for this transfer when handling and analyzing samples in practice.

Performance evaluation of disposable inhalable aerosol sampler at a copper electrorefinery.

This study evaluates the performance of the disposable inhalable aerosol sampler (DIAS), a new sampler developed to be more cost-effective than the traditional inhalable particle samplers and comparable to the inhalable particle sampling convention. Forty-eight pairs of the DIAS prototype and the IOM sampler were utilized to collect copper exposure measurements (23 personal and 25 area) at an electrorefinery facility. The geometric mean (GM) value of ratios of exposure data (DIAS/IOM) was 1.1, while the GM of ratios (DIAS/IOM) was 1.6 for the area exposure data, revealing 84% of the ratios were greater than one. For both personal and area exposure data, the concordance correlation coefficient tests revealed significant disagreements between the two types of samplers and suggested precision as the source of the disagreement. The estimated mean concentration was higher for the DIAS compared that for the IOM for the area exposure data (p < 0.05), while the results were comparable for the personal exposure data (p = 0.49). Overall, the DIAS generated higher exposure results compared to the IOM sampler for the area exposures. For the personal exposures, the findings were inconclusive due to inconsistent results of factors aforementioned. This study is limited to one metal component (copper) of the dust at a worksite. To date, this is the first field evaluation using personal exposure data to test the performance of the DIAS and the second evaluation using area exposure data. Thus, it will be necessary to conduct additional field evaluations with various elements to further evaluate the performance of the DIAS. In addition, particle migration to the internal walls of the cap was observed during the transportation of collected samples to a laboratory for both sampler types (6.4% for the DIAS and 7.4% for the IOM). Occupational health and safety professionals should be aware of potential errors caused from transferring samples from a field to a laboratory and should be careful not to exclude particles collected on the caps.

Evaluation of a portable gas chromatograph with photoionization detector under variations of VOC concentration, temperature, and relative humidity.

The objective of this present study was to evaluate the performance of a portable gas chromatograph-photoionization detector (GC-PID), under various test conditions to determine if it could be used in occupational settings. A mixture of 7 volatile organic compounds (VOCs)-acetone, ethylbenzene, methyl isobutyl ketone, toluene, m-xylene, p-xylene, and o-xylene-was selected because its components are commonly present in paint manufacturing industries. A full-factorial combination of 4 concentration levels (exposure scenarios) of VOC mixtures, 3 different temperatures (25°C, 30°C, and 35°C), and 3 relative humidities (RHs; 25%, 50%, and 75%) was conducted in a full-size controlled environmental chamber. Three repetitions were conducted for each test condition allowing for estimation of accuracy. Time-weighted average exposure data were collected using solid sorbent tubes (Anasorb 747, SKC Inc.) as the reference sampling medium. Calibration curves of Frog-4000 using the dry gases showed R2 > 0.99 for all analytes except for toluene (R2 = 0.97). Frog-4000 estimates within a test condition showed good consistency for the performance of repeated measurement. However, there was ∼41-64% reduction in the analysis of polar acetone with 75% RH relative to collection at 25% RH. Although Frog-4000 results correlated well with solid sorbent tubes (r = 0.808-0.993, except for toluene) most of the combinations regardless of analyte did not meet the <25% accuracy criterion recommended by NIOSH. The effect of chromatographic co-elution can be seen with m, p-xylene when the results are compared to the sorbent tube sampling technique with GC-flame ionization detector. The results indicated an effect of humidity on the quantification of the polar compounds that might be attributed to the pre-concentrator placed in the selected GC-PID. Further investigation may resolve the humidity effect on sorbent trap with micro GC pre-concentrator when water vapor is present. Although this instrument does not fulfill the accuracy criterion specified in the NIOSH technical report No. 2012-162, it can be used as a screening tool for range finding monitoring with dry gases calibration in the occupational setting rather than compliance monitoring.

Comparison between active (pumped) and passive (diffusive) sampling methods for formaldehyde in pathology and histology laboratories.

This study was to determine occupational exposures to formaldehyde and to compare concentrations of formaldehyde obtained by active and passive sampling methods. In one pathology and one histology laboratories, exposure measurements were collected with sets of active air samplers (Supelco LpDNPH tubes) and passive badges (ChemDisk Aldehyde Monitor 571). Sixty-six sample pairs (49 personal and 17 area) were collected and analyzed by NIOSH NMAM 2016 for active samples and OSHA Method 1007 (using the manufacturer's updated uptake rate) for passive samples. All active and passive 8-hr time-weighted average (TWA) measurements showed compliance with the OSHA permissible exposure limit (PEL-0.75 ppm) except for one passive measurement, whereas 78% for the active and 88% for the passive samples exceeded the NIOSH recommended exposure limit (REL-0.016 ppm). Overall, 73% of the passive samples showed higher concentrations than the active samples and a statistical test indicated disagreement between two methods for all data and for data without outliers. The OSHA Method cautions that passive samplers should not be used for sampling situations involving formalin solutions because of low concentration estimates in the presence of reaction products of formaldehyde and methanol (a formalin additive). However, this situation was not observed, perhaps because the formalin solutions used in these laboratories included much less methanol (3%) than those tested in the OSHA Method (up to 15%). The passive samplers in general overestimated concentrations compared to the active method, which is prudent for demonstrating compliance with an occupational exposure limit, but occasional large differences may be a result of collecting aerosolized droplets or splashes on the face of the samplers. In the situations examined in this study the passive sampler generally produces higher results than the active sampler so that a body of results from passive samplers demonstrating compliance with the OSHA PEL would be a valid conclusion. However, individual passive samples can show lower results than a paired active sampler so that a single result should be treated with caution.

Occupational exposures to new dry cleaning solvents: High-flashpoint hydrocarbons and butylal.

The dry cleaning industry is moving away from using perchloroethylene. Occupational exposures to two alternative dry cleaning solvents, butylal and high-flashpoint hydrocarbons, have not been well characterized. We evaluated four dry cleaning shops that used these alternative solvents. The shops were staffed by Korean- and Cantonese-speaking owners, and Korean-, Cantonese-, and Spanish-speaking employees. Because most workers had limited English proficiency we used language services in our evaluations. In two shops we collected personal and area air samples for butylal. We also collected air samples for formaldehyde and butanol, potential hydrolysis products of butylal. Because there are no occupational exposure limits for butylal, we assessed employee health risks using control banding tools. In the remaining two shops we collected personal and area air samples for high-flashpoint hydrocarbon solvents. In all shops the highest personal airborne exposures occurred when workers loaded and unloaded the dry cleaning machines and pressed dry cleaned fabrics. The air concentrations of formaldehyde and butanol in the butylal shops were well below occupational exposure limits. Likewise, the air concentrations of high-flashpoint hydrocarbons were also well below occupational exposure limits. However, we saw potential skin exposures to these chemicals. We provided recommendations on appropriate work practices and the selection and use of personal protective equipment. These recommendations were consistent with those derived using control banding tools for butylal. However, there is insufficient toxicological and health information to determine the safety of butylal in occupational settings. Independent evaluation of the toxicological properties of these alternative dry cleaning solvents, especially butylal, is urgently needed.

Evaluation of the dark-medium objective lens in counting asbestos fibers by phase-contrast microscopy.

A Japanese round-robin study revealed that analysts who used a dark-medium (DM) objective lens reported higher fiber counts from American Industrial Hygiene Association (AIHA) Proficiency Analytical Testing (PAT) chrysotile samples than those using a standard objective lens, but the cause of this difference was not investigated at that time. The purpose of this study is to determine any major source of this difference by performing two sets of round-robin studies. For the first round-robin study, 15 AIHA PAT samples (five each of chrysotile and amosite generated by water-suspended method, and five chrysotile generated by aerosolization method) were prepared with relocatable cover slips and examined by nine laboratories. A second round-robin study was then performed with six chrysotile field sample slides by six out of nine laboratories who participated in the first round-robin study. In addition, two phase-shift test slides to check analysts' visibility and an eight-form diatom test plate to compare resolution between the two objectives were examined. For the AIHA PAT chrysotile reference slides, use of the DM objective resulted in consistently higher fiber counts (1.45 times for all data) than the standard objective (P-value < 0.05), regardless of the filter generation (water-suspension or aerosol) method. For the AIHA PAT amosite reference and chrysotile field sample slides, the fiber counts between the two objectives were not significantly different. No statistically significant differences were observed in the visibility of blocks of the test slides between the two objectives. Also, the DM and standard objectives showed no pattern of differences in viewing the fine lines and/or dots of each species images on the eight-form diatom test plate. Among various potential factors that might affect the analysts' performance of fiber counts, this study supports the greater contrast caused by the different phase plate absorptions as the main cause of high counts for the AIHA PAT chrysotile slides using the DM objective. The comparison of fiber count ratios (DM/standard) between the AIHA PAT chrysotile samples and chrysotile field samples indicates that there is a fraction of fibers in the PAT samples approaching the theoretical limit of visibility of the phase-contrast microscope with 3-degree phase-shift. These fibers become more clearly visible through the greater contrast from the phase plate absorption of the DM objective. However, as such fibers are not present in field samples, no difference in counts between the two objectives was observed in this study. The DM objective, therefore, could be allowed for routine fiber counting as it will maintain continuity with risk assessments based on earlier phase-contrast microscopy fiber counts from field samples. Published standard methods would need to be modified to allow a higher aperture specification for the objective.

Expression of prototype foamy virus pol as a Gag-Pol fusion protein does not change the timing of reverse transcription.

Foamy viruses are retroviruses whose Pol protein is synthesized without Gag from a spliced mRNA. Unlike orthoretroviruses, reverse transcription occurs during viral assembly, leading to DNA-containing virions. When prototype foamy virus Pol is expressed as an orthoretroviral-like Gag-Pol fusion protein, reverse transcription also occurs late in viral replication, as measured by the timing of reverse transcriptase sensitivity to the inhibitor 3'-azido-3'deoxythymidine (AZT). Thus, timing of reverse transcription is intrinsic to Pol itself.

Simian foamy virus infection of rhesus macaques in Bangladesh: relationship of latent proviruses and transcriptionally active viruses.

Simian foamy viruses (SFV) are complex retroviruses that are ubiquitous in nonhuman primates (NHP) and are zoonotically transmitted to humans, presumably through NHP saliva, by licking, biting, and other behaviors. We have studied SFV in free-ranging rhesus macaques in Bangladesh. It has been previously shown that SFV in immunocompetent animals replicates to detectable levels only in superficial epithelial cells of the oral mucosa, although latent proviruses are found in most, if not all, tissues. In this study, we compare DNA sequences from latent SFV proviruses found in blood cells of 30 Bangladesh rhesus macaques to RNA sequences of transcriptionally active SFV from buccal swabs obtained from the same animals. Viral strains, defined by differences in SFV gag sequences, from buccal mucosal specimens overlapped with those from blood samples in 90% of animals. Thus, latent proviruses in peripheral blood mononuclear cells (PBMC) are, to a great extent, representative of viruses likely to be transmitted to other hosts. The level of SFV RNA in buccal swabs varied greatly between macaques, with increasing amounts of viral RNA in older animals. Evidence of APOBEC3-induced mutations was found in gag sequences derived from the blood and oral mucosa.

Evaluation of pump pulsation in respirable size-selective sampling: Part III. Investigation of European standard methods.

Lee et al. (Evaluation of pump pulsation in respirable size-selective sampling: part I. Pulsation measurements. Ann Occup Hyg 2014a;58:60-73) introduced an approach to measure pump pulsation (PP) using a real-world sampling train, while the European Standards (EN) (EN 1232-1997 and EN 12919-1999) suggest measuring PP using a resistor in place of the sampler. The goal of this study is to characterize PP according to both EN methods and to determine the relationship of PP between the published method (Lee et al., 2014a) and the EN methods. Additional test parameters were investigated to determine whether the test conditions suggested by the EN methods were appropriate for measuring pulsations. Experiments were conducted using a factorial combination of personal sampling pumps (six medium- and two high-volumetric flow rate pumps), back pressures (six medium- and seven high-flow rate pumps), resistors (two types), tubing lengths between a pump and resistor (60 and 90 cm), and different flow rates (2 and 2.5 l min(-1) for the medium- and 4.4, 10, and 11.2 l min(-1) for the high-flow rate pumps). The selection of sampling pumps and the ranges of back pressure were based on measurements obtained in the previous study (Lee et al., 2014a). Among six medium-flow rate pumps, only the Gilian5000 and the Apex IS conformed to the 10% criterion specified in EN 1232-1997. Although the AirChek XR5000 exceeded the 10% limit, the average PP (10.9%) was close to the criterion. One high-flow rate pump, the Legacy (PP=8.1%), conformed to the 10% criterion in EN 12919-1999, while the Elite12 did not (PP=18.3%). Conducting supplemental tests with additional test parameters beyond those used in the two subject EN standards did not strengthen the characterization of PPs. For the selected test conditions, a linear regression model [PPEN=0.014+0.375×PPNIOSH (adjusted R2=0.871)] was developed to determine the PP relationship between the published method (Lee et al., 2014a) and the EN methods. The 25% PP criterion recommended by Lee et al. (2014a), average value derived from repetitive measurements, corresponds to 11% PPEN. The 10% pass/fail criterion in the EN Standards is not based on extensive laboratory evaluation and would unreasonably exclude at least one pump (i.e. AirChek XR5000 in this study) and, therefore, the more accurate criterion of average 11% from repetitive measurements should be substituted. This study suggests that users can measure PP using either a real-world sampling train or a resistor setup and obtain equivalent findings by applying the model herein derived. The findings of this study will be delivered to the consensus committees to be considered when those standards, including the EN 1232-1997, EN 12919-1999, and ISO 13137-2013, are revised.

Evaluation of pump pulsation in respirable size-selective sampling: part I. Pulsation measurements.

Pulsations generated by personal sampling pumps modulate the airflow through the sampling trains, thereby varying sampling efficiencies, and possibly invalidating collection or monitoring. The purpose of this study was to characterize pulsations generated by personal sampling pumps relative to a nominal flow rate at the inlet of different respirable cyclones. Experiments were conducted using a factorial combination of 13 widely used sampling pumps (11 medium and 2 high volumetric flow rate pumps having a diaphragm mechanism) and 7 cyclones [10-mm nylon also known as Dorr-Oliver (DO), Higgins-Dewell (HD), GS-1, GS-3, Aluminum, GK2.69, and FSP-10]. A hot-wire anemometer probe cemented to the inlet of each cyclone type was used to obtain pulsation readings. The three medium flow rate pump models showing the highest, a midrange, and the lowest pulsations and two high flow rate pump models for each cyclone type were tested with dust-loaded filters (0.05, 0.21, and 1.25mg) to determine the effects of filter loading on pulsations. The effects of different tubing materials and lengths on pulsations were also investigated. The fundamental frequency range was 22-110 Hz and the magnitude of pulsation as a proportion of the mean flow rate ranged from 4.4 to 73.1%. Most pump/cyclone combinations generated pulse magnitudes ≥10% (48 out of 59 combinations), while pulse shapes varied considerably. Pulsation magnitudes were not considerably different for the clean and dust-loaded filters for the DO, HD, and Aluminum cyclones, but no consistent pattern was observed for the other cyclone types. Tubing material had less effect on pulsations than tubing length; when the tubing length was 183cm, pronounced damping was observed for a pump with high pulsation (>60%) for all tested tubing materials except for the Tygon Inert tubing. The findings in this study prompted a further study to determine the possibility of shifts in cyclone sampling efficiency due to sampling pump pulsations, and those results are reported subsequently.

Evaluation of pump pulsation in respirable size-selective sampling: part II. Changes in sampling efficiency.

This second, and concluding, part of this study evaluated changes in sampling efficiency of respirable size-selective samplers due to air pulsations generated by the selected personal sampling pumps characterized in Part I (Lee E, Lee L, Möhlmann C et al. Evaluation of pump pulsation in respirable size-selective sampling: Part I. Pulsation measurements. Ann Occup Hyg 2013). Nine particle sizes of monodisperse ammonium fluorescein (from 1 to 9 µm mass median aerodynamic diameter) were generated individually by a vibrating orifice aerosol generator from dilute solutions of fluorescein in aqueous ammonia and then injected into an environmental chamber. To collect these particles, 10-mm nylon cyclones, also known as Dorr-Oliver (DO) cyclones, were used with five medium volumetric flow rate pumps. Those were the Apex IS, HFS513, GilAir5, Elite5, and Basic5 pumps, which were found in Part I to generate pulsations of 5% (the lowest), 25%, 30%, 56%, and 70% (the highest), respectively. GK2.69 cyclones were used with the Legacy [pump pulsation (PP) = 15%] and Elite12 (PP = 41%) pumps for collection at high flows. The DO cyclone was also used to evaluate changes in sampling efficiency due to pulse shape. The HFS513 pump, which generates a more complex pulse shape, was compared to a single sine wave fluctuation generated by a piston. The luminescent intensity of the fluorescein extracted from each sample was measured with a luminescence spectrometer. Sampling efficiencies were obtained by dividing the intensity of the fluorescein extracted from the filter placed in a cyclone with the intensity obtained from the filter used with a sharp-edged reference sampler. Then, sampling efficiency curves were generated using a sigmoid function with three parameters and each sampling efficiency curve was compared to that of the reference cyclone by constructing bias maps. In general, no change in sampling efficiency (bias under ±10%) was observed until pulsations exceeded 25% for the DO cyclone. However, for three models of pumps producing 30%, 56%, and 70% pulsations, substantial changes were confirmed. The GK2.69 cyclone showed a similar pattern to that of the DO cyclone, i.e. no change in sampling efficiency for the Legacy producing 15% pulsation and a substantial change for the Elite12 producing 41% pulsation. Pulse shape did not cause any change in sampling efficiency when compared to the single sine wave. The findings suggest that 25% pulsation at the inlet of the cyclone as measured by this test can be acceptable for the respirable particle collection. If this test is used in place of that currently in European standards (EN 1232-1997 and EN 12919-1999) or is used in any International Organization for Standardization standard, then a 25% pulsation criterion could be adopted. This work suggests that a 10% criterion as currently specified in the European standards for testing may be overly restrictive and not able to be met by many pumps on the market. Further work is recommended to determine which criterion would be applicable to this test if it is to be retained in its current form.

Comparison of lead and tin concentrations in air at a solder manufacturer from the closed-face 37-mm cassette with and without a custom cellulose-acetate cassette insert.

A polyvinyl chloride (PVC) cassette insert with PVC filter (ACCU-CAP) in a 37-mm closed-face cassette (CFC) was designed for gravimetric analysis. A customized version of the ACCU-CAP, also to be used in the CFC, was manufactured from an acid-digestible cellulose-acetate cassette insert joined to a mixed cellulose ester (MCE) filter for wet chemical analysis. The aim of this study was to compare metal particle concentrations as sampled by the customized insert (CI) in a CFC sampler with the traditional sampling method using only a MCE filter in the CFC. Thirty-nine personal and 13 area samples were taken using paired filter-based CFC and the CI in CFC samplers at a solder manufacturing plant. The CI was removed from its CFC, and digested and analyzed as a whole. The MCE filter from the typical CFC was removed for analysis and then the interior of the cassette was wiped with Ghost Wipe for a separate analysis. The MCE filter only, Ghost Wipe, and CI were separately dissolved in heated nitric acid for ICP-MS analysis. Overall, the geometric mean concentration of the filter-only (FO) samples was considerably lower than that of the CI samples, by 53% for lead and 32% for tin. However, if the FO analysis was added to the corresponding Ghost Wipe analysis, i.e., filter+interior wipe (FW), the geometric mean concentrations of the FW results were similar to those of the CI results (by 113% for lead and 98% for tin). For both lead and tin the comparison of (log-transformed) metal concentrations between the FW and CI results showed no statistically significant difference (p-value = 0.3009 for lead and 0.800 for tin), while the comparison between the FO and CI results shows statistically significant differences (all p-values < 0.05). In conclusion, incorporating the sampler internal non-filter deposits by wiping or use of an internal filter capsule gave higher results than analyzing only the filter. Close agreement between the two methods of including non-filter deposits is an indication of general equivalency.

Exposure to chlorpyrifos in gaseous and particulate form in greenhouses: a pilot study.

Phase distribution of airborne chemicals is important because intake and uptake mechanisms of each phase are different. The phase distribution and concentrations are needed to determine strategies of exposure assessment, hazard control, and worker protection. However, procedures for establishing phase distribution and concentration have not been standardized. The objective of this study was to compare measurements of an airborne semivolatile pesticide (chlorpyrifos) by phase using two different procedures. Six pesticide applications in two facilities were studied and at each site, samples were collected for three time slots: T1, the first 1 or 2 hr after the commencement of application; T2, a 6-hr period immediately following T1; and T3, a 6-hr period after the required re-entry interval (24 hr for chlorpyrifos).Two phase-separating devices were co-located at the center of each greenhouse: semivolatile aerosol dichotomous sampler (SADS) using flow rates of 1.8 l x min(-1) and 0.2 l x min(-1), corresponding to a total inlet flow rate of 2.0 l x min(-1) with a vapor phase flow fraction of 0.1; and an electrostatic precipitator (ESP), along with a standard OVS XAD-2 tube. Chlorpyrifos in vapor and particulate form in a SADS sampling train and that in vapor form in an ESP sampling train were collected in OVS tubes. Chlorpyrifos in particulate form in the ESP setting would have been collected on aluminum substrate. However, no chlorpyrifos in particulate form was recovered from the ESP. Overall (vapor plus particle) concentrations measured by OVS ranged 11.7-186.6 µg/m(3) at T1 and decreased on average 77.1% and 98.9% at T2 and T3, respectively. Overall concentrations measured by SADS were 66.6%, 72.7%, and 102% of those measured by OVS on average at T1, T2, and T3, respectively. Particle fractions from the overall concentrations measured by SADS were 60.0%, 49.2%, and 13.8%, respectively, for T1, T2, and T3. SADS gives better guidance on the distribution of chlorpyrifos than does the ESP, although the accuracy of the concentration distribution cannot be verified in the absence of a standardized procedure for determining phase division.

APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's disease pathology.

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive supranuclear palsy, and one carrier was affected by AD with an unremarkable age at onset of 75 years. Two APOE ε3/ε4 controls carried a stop-gain affecting ε4: one was cognitively normal at 90 years and had no neuritic plaques at autopsy; the other was cognitively healthy at 79 years, and lumbar puncture at 76 years showed normal levels of amyloid. These results suggest that ε4 drives AD risk through the gain of abnormal function and support ε4 knockdown as a viable therapeutic option.

Foamy virus Pol protein expressed as a Gag-Pol fusion retains enzymatic activities, allowing for infectious virus production.

Foamy viruses (FV) synthesize Pol from a spliced pol mRNA independently of Gag, unlike orthoretroviruses, which synthesize Pol as a Gag-Pol protein that coassembles with Gag. We found that prototype FV (PFV) mutants expressing Gag and Pol only as a Gag-Pol protein without the spliced Pol contain protease activity equivalent to that of wild-type (WT) Pol. Regardless of the presence or absence of the spliced Pol, the PFV Gag-Pol proteins can assemble into virus-like particles (VLPs), in contrast to the orthoretroviral Gag-Pol proteins, which cannot form VLPs. However, the PFV Gag-Pol VLPs have aberrant morphologies and are not infectious. In the absence of the spliced Pol, coexpression of a PFV Gag-Pol protein with Gag can produce infectious virions. Our results suggest that enzymes encoded by PFV pol (protease, reverse transcriptase, and integrase) are enzymatically active if they are synthesized as part of a Gag-Pol protein.

Exposure models for the prior distribution in bayesian decision analysis for occupational hygiene decision making.

This study introduces two semi-quantitative methods, Structured Subjective Assessment (SSA) and Control of Substances Hazardous to Health (COSHH) Essentials, in conjunction with two-dimensional Monte Carlo simulations for determining prior probabilities. Prior distribution using expert judgment was included for comparison. Practical applications of the proposed methods were demonstrated using personal exposure measurements of isoamyl acetate in an electronics manufacturing facility and of isopropanol in a printing shop. Applicability of these methods in real workplaces was discussed based on the advantages and disadvantages of each method. Although these methods could not be completely independent of expert judgments, this study demonstrated a methodological improvement in the estimation of the prior distribution for the Bayesian decision analysis tool. The proposed methods provide a logical basis for the decision process by considering determinants of worker exposure.

Evaluation of Stoffenmanager® and ART for Estimating Occupational Inhalation Exposures to Volatile Liquids.

In practice, workers often handle the same chemical(s) of interest under different control measures (e.g. local ventilation, enclosed system) during a full shift. Stoffenmanager® allows users to predict either task-based or full-shift exposures. However, most previous studies evaluated the tool by comparing task-based exposures with measured exposures. Also, limited evaluation studies of the Advanced REACH Tool (ART) with the Bayesian approach (ART+B) are available, requiring additional evaluation studies. The performance of Stoffenmanager® and ART with and without the Bayesian approach was evaluated with measured full-shift exposures to volatile liquids in terms of accuracy, precision, and conservatism. Forty-two exposure situation scenarios (including 251 exposures), developed based on job tasks and chemicals handled during tasks from workplaces, were used to generate full-shift estimates. The estimates were then compared with measured exposures using various comparison methods. Overall, Stoffenmanager® appeared to be the most accurate among the testing tools, while ART+B was the most precise. The percentage of measured exposures exceeding the tools' 90th percentile estimates (%M>T) demonstrated that Stoffenmanager® (16%M>T) and ART+B (13%M>T) were more conservative than ART (41%M>T). When the 90% upper confidence limit of the 90th percentile estimate was considered, the level of conservatism changed from low (41%M>T) to medium (17%M>T) for ART and from medium (13%M>T) to high (0.8%M>T) for ART+B. The findings of this study indicate that no single tool would work for all ESs. Thus, it is recommended that users select a tool based on the performance results of three components (i.e. accuracy, precision, and conservatism), not depending on one or two components. The strength of this study is that the required tools' input parameters were obtained during the sample collection to minimize assumptions for many input parameters. In addition, unlike other previous studies, multiple subtasks, which happen often in workplaces, were incorporated in this study. Nevertheless, the present study did not cover all activities listed in the tools and was limited to volatile liquids, suggesting further studies cover other exposure categories (e.g. solid, metal) and diverse activities.