Search

Rationale: Recent U.S. data suggest an increased risk of work-related asthma among health care workers, yet only a few specific determinants have been elucidated.Objectives: To evaluate associations of asthma prevalence with occupational exposures in a cross-sectional survey of health care professionals.Methods: A detailed questionnaire was mailed to a random sample (n=5,600) of all Texas physicians, nurses, respiratory therapists, and occupational therapists with active licenses in 2003. Information on asthma symptoms and nonoccupational asthma risk factors obtained from the questionnaire was linked to occupational exposures derived through an industry-specific job-exposure matrix.Measurements: There were two a priori defined outcomes: (1) physician-diagnosed asthma with onset after entry into health care ("reported asthma") and (2) "bronchial hyperresponsiveness-related symptoms," defined through an 8-item symptom-based predictor.Main Results: Overall response rate was 66%. The final study population consisted of 862 physicians, 941 nurses, 968 occupational therapists, and 879 respiratory therapists (n=3,650). Reported asthma was associated with medical instrument cleaning (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.34-3.67), general cleaning (OR, 2.02; 95% CI, 1.20-3.40), use of powdered latex gloves between 1992 and 2000 (OR, 2.17; 95% CI, 1.27-3.73), and administration of aerosolized medications (OR, 1.72; 95% CI, 1.05-2.83). The risk associated with latex glove use was not apparent after 2000. Bronchial hyperresponsiveness-related symptoms were associated with general cleaning (OR, 1.63; 95% CI, 1.21-2.19), aerosolized medication administration (OR, 1.40; 95% CI, 1.06-1.84), use of adhesives on patients (OR, 1.65; 95% CI, 1.22-2.24), and exposure to a chemical spill (OR, 2.02; 95% CI, 1.28-3.21).Conclusions: The contribution of occupational exposures to asthma in health care professionals is not trivial, meriting both implementation of appropriate controls and further study. [ABSTRACT FROM AUTHOR]

Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo., (© 2024. The Author(s).)

H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both SUV39H1 and SUV39H2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyze heterochromatic H3K9me3 deposition. We reveal a paradoxical repression of protein-coding genes in Suv39DKO cells, with these differentially expressed genes principally in euchromatic (Tn5-accessible, H3K4me3- and H3K27ac-marked) rather than heterochromatic (H3K9me3-marked) or polycomb (H3K27me3-marked) regions. Examination of the three-dimensional (3D) nucleome reveals that transcriptomic dysregulation occurs in euchromatic regions close to the nuclear periphery in 3D space. Moreover, this transcriptomic dysregulation is highly correlated with altered 3D genome organization in Suv39DKO cells. Together, our results suggest that the nuclear lamina-tethering of Suv39-dependent H3K9me3 domains provides an essential scaffold to support euchromatic genome organization and the maintenance of gene transcription for healthy cellular function., (© 2024 Keenan et al.; Published by Cold Spring Harbor Laboratory Press.)

EphB6 is an understudied ephrin receptor tyrosine pseudokinase that is downregulated in multiple types of metastatic cancers. Unlike its kinase-active counterparts which autophosphorylate and transmit signals upon intercellular interaction, little is known about how EphB6 functions in the absence of intrinsic kinase activity. Here, we unveil a molecular mechanism of cell-cell interaction driven by EphB6. We identify ephrinB1 as a cognate ligand of EphB6 and show that in trans interaction of EphB6 with ephrinB1 on neighboring cells leads to the formation of large co-clusters at the plasma membrane. These co-clusters exhibit a decreased propensity towards endocytosis, suggesting a unique characteristic for this type of cell-cell interaction. Using lattice light-sheet microscopy, 3D structured illumination microscopy and cryo-electron tomography techniques, we show that co-clustering of EphB6 and ephrinB1 promotes the formation of double-membrane tubular structures between cells. Importantly, we also demonstrate that these intercellular structures stabilize cell-cell adhesion, leading to a reduction in the invasive behavior of cancer cells. Our findings rationalize a role for EphB6 pseudokinase as a tumor suppressor when interacting with its ligands in trans., (© 2024. The Author(s).)

Objective: Health care workers are at risk for work-related asthma, which may be affected by changes in cleaning practices. We examined associations of cleaning tasks and products with work-related asthma in health care workers in 2016, comparing them with prior results from 2003., Methods: We estimated asthma prevalence by professional group and explored associations of self-reported asthma with job-exposure matrix-based cleaning tasks/products in a representative Texas sample of 9914 physicians, nurses, respiratory/occupational therapists, and nurse aides., Results: Response rate was 34.8% (n = 2421). The weighted prevalence rates of physician-diagnosed (15.3%), work-exacerbated (4.1%), and new-onset asthma (6.7%) and bronchial hyperresponsiveness symptoms (31.1%) were similar to 2003. New-onset asthma was associated with building surface cleaning (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.10-3.33), use of ortho-phthalaldehyde (OR, 1.77; 95% CI, 1.15-2.72), bleach/quaternary compounds (OR, 1.91; 95% CI, 1.10-3.33), and sprays (OR, 1.97; 95% CI, 1.12-3.47)., Conclusion: Prevalence of asthma/bronchial hyperresponsiveness seems unchanged, whereas associations of new-onset asthma with exposures to surface cleaning remained, and decreased for instrument cleaning., Competing Interests: Conflicts of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Background: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology., Methods: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of MPXV. We designed a panel of 22 primer-guide RNA sets using pangenome and gene-agnostic approaches, and subsequently shortlisted the three sets producing the strongest signals for evaluation of analytical sensitivity and specificity using a fluorescence-based readout. The set displaying 100% specificity and the lowest limit of detection (LOD) was selected for further assay validation using both a fluorescence-based and lateral-flow readout. Assay specificity was confirmed using a panel of viral and bacterial pathogens. Finally, we did a blind concordance study on genomic DNA extracted from 185 clinical samples, comparing assay results with a gold-standard quantitative PCR (qPCR) assay. We identified the optimal time to detection and analysed the performance of the assay relative to qPCR using receiver operating characteristic (ROC) curves. We also assessed the compatibility with lateral-flow strips, both visually and computationally, where strips were interpreted blinded to the fluorescence results on the basis of the presence or absence of test bands., Findings: With an optimal run duration of approximately 45 min from isothermal amplification to CRISPR-assay readout, the MPXV recombinase polymerase amplification CRISPR-Cas12a-based assay with the selected primer-guide set had an LOD of 1 copy per μL and 100% specificity against tested viral pathogens. Blinded concordance testing of 185 clinical samples resulted in 100% sensitivity (95% CI 89·3-100) and 99·3% specificity (95% CI 95·7-100) using the fluorescence readout. For optimal time to detection by fluorescence readout, we estimated the areas under the ROC curve to be 0·98 at 2 min and 0·99 at 4 min. Lateral-flow strips had 100% sensitivity (89·3-100) and 98·6% specificity (94·7-100) with both visual and computational assessment. Overall, lateral-flow results were highly concordant with fluorescence-based readouts (179 of 185 tests, 96·8% concordant), with discrepancies associated with low viral load samples., Interpretation: Our assay for the diagnosis of mpox displayed good performance characteristics compared with qPCR. Although optimisation of the assay will be required before deployment, its usability and versatility present a potential solution to MPXV detection in low-resource and remote settings, as well as a means of community-based, on-site testing., Funding: Victorian Medical Research Accelerator Fund and the Australian Government Department of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license. Published by Elsevier Ltd.. All rights reserved.)

The promise of single-objective light-sheet microscopy is to combine the convenience of standard single-objective microscopes with the speed, coverage, resolution and gentleness of light-sheet microscopes. We present DaXi, a single-objective light-sheet microscope design based on oblique plane illumination that achieves: (1) a wider field of view and high-resolution imaging via a custom remote focusing objective; (2) fast volumetric imaging over larger volumes without compromising image quality or necessitating tiled acquisition; (3) fuller image coverage for large samples via multi-view imaging and (4) higher throughput multi-well imaging via remote coverslip placement. Our instrument achieves a resolution of 450 nm laterally and 2 μm axially over an imaging volume of 3,000 × 800 × 300 μm. We demonstrate the speed, field of view, resolution and versatility of our instrument by imaging various systems, including Drosophila egg chamber development, zebrafish whole-brain activity and zebrafish embryonic development - up to nine embryos at a time., (© 2022. The Author(s).)

Toxoplasma gondii develops a latent infection in the muscle and central nervous system that acts as a reservoir for acute-stage reactivation in vulnerable patients. Little is understood about how parasites manipulate host cells during latent infection and the impact this has on survival. We show that bradyzoites impart a unique transcriptional signature on infected host cells. Many of these transcriptional changes rely on protein export and result in the suppression of type I interferon (IFN) and IFNγ signaling more so than in acute stages. Loss of the protein export component, MYR1, abrogates transcriptional remodeling and prevents suppression of IFN signaling. Among the exported proteins, the inhibitor of STAT1 transcription (IST) plays a key role in limiting IFNγ signaling in bradyzoites. Furthermore, bradyzoite protein export protects host cells from IFNγ-mediated cell death, even when export is restricted to latent stages. These findings highlight the functional importance of host manipulation in Toxoplasma's bradyzoite stages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Necroptosis is a lytic, inflammatory cell death pathway that is dysregulated in many human pathologies. The pathway is executed by a core machinery comprising the RIPK1 and RIPK3 kinases, which assemble into necrosomes in the cytoplasm, and the terminal effector pseudokinase, MLKL. RIPK3-mediated phosphorylation of MLKL induces oligomerization and translocation to the plasma membrane where MLKL accumulates as hotspots and perturbs the lipid bilayer to cause death. The precise choreography of events in the pathway, where they occur within cells, and pathway differences between species, are of immense interest. However, they have been poorly characterized due to a dearth of validated antibodies for microscopy studies. Here, we describe a toolbox of antibodies for immunofluorescent detection of the core necroptosis effectors, RIPK1, RIPK3, and MLKL, and their phosphorylated forms, in human and mouse cells. By comparing reactivity with endogenous proteins in wild-type cells and knockout controls in basal and necroptosis-inducing conditions, we characterise the specificity of frequently-used commercial and recently-developed antibodies for detection of necroptosis signaling events. Importantly, our findings demonstrate that not all frequently-used antibodies are suitable for monitoring necroptosis by immunofluorescence microscopy, and methanol- is preferable to paraformaldehyde-fixation for robust detection of specific RIPK1, RIPK3, and MLKL signals.

Host membrane remodeling is indispensable for viruses, bacteria, and parasites, to subvert the membrane barrier and obtain entry into cells. The malaria parasite Plasmodium spp. induces biophysical and molecular changes to the erythrocyte membrane through the ordered secretion of its apical organelles. To understand this process and address the debate regarding how the parasitophorous vacuole membrane (PVM) is formed, we developed an approach using lattice light-sheet microscopy, which enables the parasite interaction with the host cell membrane to be tracked and characterized during invasion. Our results show that the PVM is predominantly formed from the erythrocyte membrane, which undergoes biophysical changes as it is remodeled across all stages of invasion, from pre-invasion through to PVM sealing. This approach enables a functional interrogation of parasite-derived lipids and proteins in PVM biogenesis and echinocytosis during Plasmodium falciparum invasion and promises to yield mechanistic insights regarding how this is more generally orchestrated by other intracellular pathogens.

Objectives: Job exposure matrices (JEMs) are important tools for estimating occupational exposures in study populations where only information on industry and occupation (I&O) are available. JEMs The objective of this work was to create JEMs for solar and artificial ultraviolet radiation (UVR) using a US standardized coding scheme., Methods: Using U.S. Census Bureau industry and occupation codes, separate lists of I&O pairs were developed for solar and artificial UVR by a panel of Certified Industrial Hygienists who assigned exposure ratings to I&O pairs with potential exposure. Parameters for exposure included prevalence (P) and frequency (F) for solar UVR and P, F, and intensity (I) for artificial UVR. Prevalence, or percent of all workers employed in an I&O pair who were exposed, was categorically rated: 0 to <1, 1 to <20; 20 to <80, and ≥80. Frequency of exposure, defined by the number of hours per week workers were exposed, was categorically rated: 0 to <5, 5 to <20, 20 to <35, and ≥35 h per week. For artificial UVR only, intensity of exposure was assigned three ratings: low, low with rare excursions, and >low under normal conditions. Discrepant ratings were resolved via consensus., Results: After excluding I&O pairs assigned P and F ratings of 0 (solar UVR) and P, F, and I ratings of 0 (artificial UVR) from the JEM, 9206 I&O pairs were rated for solar UVR and 2010 I&O pairs for artificial UVR. For solar UVR, 723 (7.9% of all rated pairs) had ratings in the highest category for P and F; this group included 45 occupations in varied industries. Construction and extraction occupations represented most of the occupations (n = 20; 44%), followed by farming, fishing, and forestry occupations (n = 6; 13%). For artificial UVR, 87 I&O pairs (4.3% of all rated pairs) had maximum ratings for P, F, and I; these comprised a single occupation (welding, soldering, and brazing workers) in diverse industries., Conclusions: JEMs for solar and artificial UVR were developed for a broad range of I&O pairs in the US population and are available for use by researchers conducting occupational epidemiological studies., (Published by Oxford University Press on behalf of the British Occupational Hygiene Society 2020.)

Truncating mutations in the tumour suppressor gene APC occur frequently in colorectal cancers and result in the deregulation of Wnt signalling as well as changes in cell-cell adhesion. Using quantitative imaging based on the detection of membrane-associated E-cadherin, we undertook a protein coding genome-wide siRNA screen to identify genes that regulate cell surface E-cadherin in the APC-defective colorectal cancer cell line SW480. We identified a diverse set of regulators of E-cadherin that offer new insights into the regulation of cell-cell adhesion, junction formation and genes that regulate proliferation or survival of SW480 cells. Among the genes whose depletion promotes membrane-associated E-cadherin, we identified ZEB1, the microRNA200 family, and proteins such as a ubiquitin ligase UBE2E3, CDK8, sorting nexin 27 (SNX27) and the matrix metalloproteinases, MMP14 and MMP19. The screen also identified 167 proteins required for maintaining E-cadherin at cell-cell adherens junctions, including known junctional proteins, CTNND1 and CTNNA1, as well as signalling enzymes, DUSP4 and MARK2, and transcription factors, TEAD3, RUNX2 and TRAM2. A better understanding of the post-translational regulation of E-cadherin provides new opportunities for restoring cell-cell adhesion in APC-defective cells., Competing Interests: The authors have declared that no competing interests exist.

Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation is thought to initiate MLKL oligomerization, membrane translocation and membrane disruption, although the precise choreography of events is incompletely understood. Here, we use single-cell imaging approaches to map the chronology of endogenous human MLKL activation during necroptosis. During the effector phase of necroptosis, we observe that phosphorylated MLKL assembles into higher order species on presumed cytoplasmic necrosomes. Subsequently, MLKL co-traffics with tight junction proteins to the cell periphery via Golgi-microtubule-actin-dependent mechanisms. MLKL and tight junction proteins then steadily co-accumulate at the plasma membrane as heterogeneous micron-sized hotspots. Our studies identify MLKL trafficking and plasma membrane accumulation as crucial necroptosis checkpoints. Furthermore, the accumulation of phosphorylated MLKL at intercellular junctions accelerates necroptosis between neighbouring cells, which may be relevant to inflammatory bowel disease and other necroptosis-mediated enteropathies.

Purpose: Exposure to organic solvents and noise may be causal agents in the development of hearing loss and tinnitus. The objectives of the present study were to examine the association of organic solvents with hearing loss and tinnitus and to assess the interaction of organic solvent and occupational noise exposure on hearing loss and tinnitus., Methods: A secondary data analysis of data from the National Health and Nutrition Examination Survey and Occupational Information Network (O*NET) among a study population ranging from 1085 to 2471 study participants from 1999 to 2004. Multiple multivariate logistic regression models were used to assess the associations of individual organic solvent exposures as measured by blood biomarkers (1,4-dichlorobenzene, benzene, ethylbenzene, styrene, toluene, o-xylene, and m-/p-xylene) with self-reported hearing loss, audiometrically assessed hearing loss, and self-reported tinnitus. Models were adjusted for age, gender, race/ethnicity, diabetes, non-occupational noise exposure, smoking, and income. Organic solvents found to be statistically significantly associated with the outcome after adjusting for covariates were tested for interaction with occupational noise exposure., Results: Solvent exposure was not statistically significantly associated with self-reported tinnitus. Benzene (OR 1.43, 95% CI 1.15-1.78), ethylbenzene (OR 1.24, 95% CI 1.02-1.50), and toluene (OR 1.27, 95% CI 1.06-1.52) concentrations were statistically significantly associated with increased adjusted odds of high-frequency hearing loss. No statistically significant interaction was observed between these solvents and occupational noise on high-frequency hearing loss., Conclusions: We found no evidence of an association between organic solvents and tinnitus; however, there was evidence of an association between organic solvent exposure and prevalence of high-frequency hearing loss.

While many organizations maintain multiple layers of security control methodologies to prevent outsiders from gaining unauthorized access, persons such as employees or contractors who have been granted legitimate access can represent an "insider threat" risk. Interestingly, some of the most notable radiological events involving the purposeful contamination or exposure of individuals appear to have been perpetrated by insiders. In the academic and medical settings, radiation safety professionals focus their security efforts on (1) ensuring controls are in place to prevent unauthorized access or removal of sources, and (2) increasing security controls for the unescorted accessing of large sources of radioactivity (known as "quantities of concern"). But these controls may not completely address the threat insiders represent when radioactive materials below these quantities are present. The goal of this research project was to characterize the methodologies currently employed to counteract the insider security threat for the misuse or purposeful divergence of radioactive materials used in the academic and medical settings. A web-based survey was used to assess how practicing radiation safety professionals in academic and medical settings anticipate, evaluate, and control insider threat security risks within their institutions. While all respondents indicated that radioactive sources are being used in amounts below quantities of concern, only 6 % consider insider threat security issues as part of the protocol review for the use of general radioactive materials. The results of this survey identify several opportunities for improvement for institutions to address security gaps.

Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed tophi of chronic gout patients. We developed a quantitative, live cell imaging assay, which measures the key features of NETosis, namely, cell death and chromatin decondensation. We show that MSU and other physiologically relevant crystals induce NETosis through a molecular pathway that is distinct from PMA and Candida hyphae. Crystals interact with lysosomes to induce NADPH oxidase-independent cell death, with postmortem chromatin decondensation mediated by neutrophil elastase. The resulting MSU-induced NETs are enriched for actin and are resistant to serum and DNase degradation. These findings demonstrate a distinct physiological NETosis pathway in response to MSU crystals, which coats MSU crystals in DNA that persists in tissues as gouty tophi., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release and activation of apoptotic caspases. In the absence of active caspases, mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear. We used live-cell lattice light-sheet microscopy to examine the mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX activation and cytochrome c loss, the mitochondrial network broke down and large BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed the inner mitochondrial membrane to herniate into the cytosol, carrying with it mitochondrial matrix components, including the mitochondrial genome. Apoptotic caspases did not prevent herniation but dismantled the dying cell to suppress mtDNA-induced innate immune signaling., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice. These defects can be attributed to destabilization and incorrect trafficking of proteins bearing thrombospondin repeats (TSRs). Therefore, POFUT2 plays a similar role in malaria parasites to that in metazoans: it ensures the trafficking of Plasmodium TSR proteins as part of a non-canonical glycosylation-dependent endoplasmic reticulum protein quality control mechanism.The role of O-glycosylation in the malaria life cycle is largely unknown. Here, the authors identify a Plasmodium protein O-fucosyltransferase and show that it is important for normal trafficking of a subset of surface proteins, particularly CSP and TRAP, and efficient infection of mosquito and vertebrate hosts.

In just over a decade, the field of biomedical research has witnessed a radical evolution in technologies for the 3- and 4-dimensional imaging of biological samples. Light sheet fluorescence microscopy is quickly developing into a powerful approach for fast, volumetric imaging of cells, tissues and living organisms. This review touches on the development of 3-dimensional imaging, from its foundations, namely from the invention of confocal microscopy in the twentieth century to more recent examples, notably the IsoView SPIM, the Lattice Light Sheet Microscope and swept confocally aligned planar excitation. These technologies overcome the limitations of conventional optical sectioning techniques and enable unprecedented levels of spatio-temporal resolution with low levels of phototoxicity. Developing in parallel with powerful computational approaches, light sheet based methods promise to completely transform cell biology as we know it today.

Objectives: To perform a case-control study of maternal occupational physical activity and risk for orofacial clefts in Texas during 1999-2009., Methods: We used logistic regression to assess 14 measures of physical activity estimated from a job exposure matrix, using the maternal occupation reported on the birth certificate, among 887 children with cleft lip with or without cleft palate (CLP), 436 children with cleft palate only (CP), and 1932 controls., Results: After adjusting for several potential confounders, seven measures of physical activity (as a categorical and/or continuous variable) were significantly associated with CLP, CP, or both. Positive associations were seen for keeping balance, kneeling, standing, and walking/running (odds ratio 95% confidence interval range 1.0-1.9 for fourth versus first quartile). A significant positive trend was also seen for bending/twisting. Negative associations were seen for repetitive motion and sitting., Conclusions: Maternal occupational physical activity may be related to the etiology of orofacial clefts., (© 2017 Wiley Periodicals, Inc.)

Introduction: Previous studies found that aircraft maintenance workers may be exposed to organophosphates in hydraulic fluid and engine oil. Studies have also illustrated a link between long-term low-level organophosphate pesticide exposure and depression., Methods: A questionnaire containing the Patient Health Questionnaire 8 depression screener was e-mailed to 52,080 aircraft maintenance workers (with N = 4801 complete responses) in a cross-sectional study to determine prevalence and severity of depression and descriptions of their occupational exposures., Results: There was no significant difference between reported depression prevalence and severity in similar exposure groups in which aircraft maintenance workers were exposed or may have been exposed to organophosphate esters compared to similar exposure groups in which they were not exposed. However, a dichotomous measure of the prevalence of depression was significantly associated with self-reported exposure levels from low (OR: 1.21) to moderate (OR: 1.68) to high exposure (OR: 2.70) and with each exposure route including contact (OR: 1.68), inhalation (OR: 2.52), and ingestion (OR: 2.55). A self-reported four-level measure of depression severity was also associated with a self-reported four-level measure of exposure., Discussion: Based on self-reported exposures and outcomes, an association is observed between organophosphate exposure and depression; however, we cannot assume that the associations we observed are causal because some workers may have been more likely to report exposure to organophosphate esters and also more likely to report depression. Future studies should consider using a larger sample size, better methods for characterizing crew chief exposures, and bioassays to measure dose rather than exposure. Hardos JE, Whitehead LW, Han I, Ott DK, Waller DK. Depression prevalence and exposure to organophosphate esters in aircraft maintenance workers. Aerosp Med Hum Perform. 2016; 87(8):712-717.

Plasmodium falciparum parasites in the merozoite stage invade human erythrocytes and cause malaria. Invasion requires multiple interactions between merozoite ligands and erythrocyte receptors. P. falciparum reticulocyte binding homolog 5 (PfRh5) forms a complex with the PfRh5-interacting protein (PfRipr) and Cysteine-rich protective antigen (CyRPA) and binds erythrocytes via the host receptor basigin. However, the specific role that PfRipr and CyRPA play during invasion is unclear. Using P. falciparum lines conditionally expressing PfRipr and CyRPA, we show that loss of PfRipr or CyRPA function blocks growth due to the inability of merozoites to invade erythrocytes. Super-resolution microscopy revealed that PfRipr, CyRPA, and PfRh5 colocalize at the junction between merozoites and erythrocytes during invasion. PfRipr, CyRPA, and PfRipr/CyRPA/PfRh5-basigin complex is required for triggering the Ca(2+) release and establishing the tight junction. Together, these results establish that the PfRh5/PfRipr/CyRPA complex is essential in the sequential molecular events leading to parasite invasion of human erythrocytes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: An increasing number of radiologic exams are performed in the United States, but very few studies have examined the effects of maternal exposure to radiologic exams during the periconceptional period and birth defects., Objectives: To assess the association between maternal exposure to radiologic exams during the periconceptional period and 19 categories of birth defects using a large population-based study of birth defects., Methods: We studied 27,809 case mothers and 10,200 control mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. Maternal exposure to radiologic exams that delivered ionizing radiation to the urinary tract, lumbar spine, abdomen, or pelvis were identified based on the mother's report of type of radiologic exams, organ or body part scanned and the month during which the exam occurred, Results: Overall, 0.9% of mothers reported exposure to one of these types of radiographic exams during the periconceptional period. We observed significant associations between maternal exposure during the first trimester and isolated Dandy-Walker malformation (odds ratio = 7.7; 95% confidence interval, 1.8-33) and isolated d-transposition of the great arteries (odds ratio = 3.8; 95% confidence interval, 1.4-10.3). However, the result for isolated Dandy-Walker malformation was based on only two exposed cases., Conclusion: These results should be interpreted cautiously because multiple statistical tests were conducted and measurements of exposure were based on maternal report. However, our results may be useful for generating hypotheses for future studies. Birth Defects Research (Part A) 106:563-572, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein diet, but not when mice are fed a HFD with low energy density (high fiber). Furthermore, mice with an activating mutation in NLRP1, and hence increased IL-18, have decreased adiposity and are resistant to diet-induced metabolic dysfunction. Feeding these mice a HFD further increased plasma IL-18 concentrations and strikingly resulted in loss of adipose tissue mass and fatal cachexia, which could be prevented by genetic deletion of IL-18. Thus, NLRP1 is an innate immune sensor that functions in the context of metabolic stress to produce IL-18, preventing obesity and metabolic syndrome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects., Methods: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects., Results: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy., Conclusion: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies., (© 2015 Wiley Periodicals, Inc.)

Because the origins of the biological safety profession are rooted in the control and prevention of laboratory-associated infections, the vocation focuses primarily on the safe handling of specimens within the laboratory. But in many cases, the specimens and samples handled in the lab are originally collected in the field where a broader set of possible exposure considerations may be present, each with varying degrees of controllability. The failure to adequately control the risks associated with collecting biological specimens in the field may result in illness or injury, and could have a direct impact on laboratory safety, if infectious specimens were packaged or transported inappropriately, for example. This study developed a web-based survey distributed to practicing biological safety professionals to determine the prevalence of and extent to which biological safety programs consider and evaluate field collection activities. In cases where such issues were considered, the data collected characterize the types of controls and methods of oversight at the institutional level that are employed. Sixty-one percent (61%) of the survey respondents indicated that research involving the field collection of biological specimens is conducted at their institutions. A majority (79%) of these field collection activities occur at academic institutions. Twenty-seven percent (27%) of respondents indicated that their safety committees do not consider issues related to biological specimens collected in the field, and only 25% with an oversight committee charged to review field collection protocols have generated a field research-specific risk assessment form to facilitate the assembly of pertinent information for a project risk assessment review. The results also indicated that most biosafety professionals (73% overall; 71% from institutions conducting field collection activities) have not been formally trained on the topic, but many (64% overall; 87% from institutions conducting field collection activities) indicated that training on field research safety issues would be helpful, and even more (71% overall; 93% from institutions conducting field collection activities) would consider participation in such a training course. Results obtained from this study can be used to develop a field research safety toolkit and associated training curricula specifically targeted to biological safety professionals.

Although studies have examined the relation between military-related noise and hearing, comprehensive data to calculate rates of hearing loss across all Services and to determine economic impact are lacking. The goal of the multiphase Department of Defense (DoD) Epidemiologic and Economic Burden of Hearing Loss (DEEBoHL) project is to examine rates of hearing impairment and noise-induced hearing injury, relevant noise exposures, and to determine the economic burden of these outcomes to the DoD and Service Members. The DoD Hearing Center of Excellence is supporting the following Phase I specific aims, among active duty Service Members to (1) calculate rates of hearing impairment and noise-induced hearing injury, and (2) develop a framework for the DoD to conduct comprehensive economic burden studies for hearing impairment and noise-induced hearing injury. The study is led by a multidisciplinary team from The University of Texas School of Public Health, The University of Texas Health Science Center at San Antonio, and The Geneva Foundation, with guidance from experts who make up the study advisory board. In this article, we focus on an overview of the DEEBoHL study, the methods for the first aim of this effort, and describe future plans for the study., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

In this study, we test the assumption that the hematopoietic progenitor/colony-forming cells of the embryonic yolk sac (YS), which are endowed with megakaryocytic potential, differentiate into the first platelet-forming cells in vivo. We demonstrate that from embryonic day (E) 8.5 all megakaryocyte (MK) colony-forming cells belong to the conventional hematopoietic progenitor cell (HPC) compartment. Although these cells are indeed capable of generating polyploid MKs, they are not the source of the first platelet-forming cells. We show that proplatelet formation first occurs in a unique and previously unrecognized lineage of diploid platelet-forming cells, which develop within the YS in parallel to HPCs but can be specified in the E8.5 Runx1-null embryo despite the absence of the progenitor cell lineage., (© 2014 by The American Society of Hematology.)

The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed PEXEL cleavage occurs cotranslationaly, similar to signal peptidase. Treatment of P. falciparum-infected erythrocytes with the inhibitor caused dose-dependent inhibition of PEXEL processing as well as protein export, including impaired display of the major virulence adhesin, PfEMP1, on the erythrocyte surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target., Competing Interests: The authors have declared that no competing interests exist.

Given disproportionate burden of physical inactivity among US Hispanics and emerging interests in the potential role of the built environment on physical activity, we tested the hypothesis that residing in a more walkable block group is associated with increased physical activity in a cohort of Mexican-American adults. 10,183 Mexican-American adults from Houston, TX, USA were studied. Physical activity was assessed through self-report. Geographical information systems were used to create a "walkability index" (WI). We examined the relationship between WI and physical activity using regression models. Findings for the entire study population suggested a direct association between neighborhood walkability and physical activity that approached statistical significance (High WI vs. Low WI: OR = 1.16; 95% CI 0.95-1.40). Furthermore, participants who lived in a higher WI neighborhood were more likely to meet physical activity guidelines in 2 groups: (1) men whose recreational physical activity included walking (High WI vs. Low WI: OR = 5.43; 95% CI 1.30-22.73) and (2) men whose only recreational physical activity was (High WI vs. Low WI: OR = 9.54; 95% CI 1.84-49.60). Our findings suggest gender differences in the association between the built environment and physical activity in Mexican-American adults. Attempts to encourage walking among Mexican-American adults may be easier in high-walkability neighborhoods than in low-walkability neighborhoods.

The measured spatial coherence characteristics of the illumination used in a diffractive imaging experiment are incorporated in an algorithm that reconstructs the complex transmission function of an object from experimental x-ray diffraction data using 1.4 keV x rays. Conventional coherent diffractive imaging, which assumes full spatial coherence, is a limiting case of our approach. Even in cases in which the deviation from full spatial coherence is small, we demonstrate a significant improvement in the quality of wave field reconstructions. Our formulation is applicable to x-ray and electron diffraction imaging techniques provided that the spatial coherence properties of the illumination are known or can be measured.

Background: Previous studies have described increased occurrence of asthma among healthcare workers, but to our knowledge there are no validated survey questionnaires with which to study this occupational group., Aims: To develop, validate, and refine a new survey instrument on asthma for use in epidemiological studies of healthcare workers., Methods: An initial draft questionnaire, designed by a multidisciplinary team, used previously validated questions where possible; the occupational exposure section was developed by updating health services specific chemical lists through hospital walk-through surveys and review of material safety data sheets. A cross-sectional validation study was conducted in 118 non-smoking subjects, who also underwent bronchial challenge testing, an interview with an industrial hygienist, and measurement of specific IgE antibodies to common aeroallergens., Results: The final version consisted of 43 main questions in four sections. Time to completion of the questionnaire ranged from 13 to 25 minutes. Test-retest reliability of asthma and allergy items ranged from 75% to 94%, and internal consistency for these items was excellent (Cronbach's alpha > or = 0.86). Against methacholine challenge, an eight item combination of asthma related symptoms had a sensitivity of 71% and specificity of 70%; against a physician diagnosis of asthma, this same combination showed a sensitivity of 79% and specificity of 98%. Agreement between self-reported exposures and industrial hygienist review was similar to previous studies and only moderate, indicating the need to incorporate more reliable methods of exposure assessment. Against the aerollergen panel, the best combinations of sensitivity and specificity were obtained for a history of allergies to dust, dust mite, and animals., Conclusions: Initial evaluation of this new questionnaire indicates good validity and reliability, and further field testing and cross-validation in a larger healthcare worker population is in progress. The need for development of more reliable occupational exposure assessment methods that go beyond self-report is underscored.

Case reports describing sources of radioactivity lost downhole in Texas from 1956 to 2001 were obtained from the Texas Department of Health Bureau of Radiation Control and entered into a computerized database. The events of the 45-y period of analysis were characterized, examining aspects such as source type, amount of activity, location of loss, depth, and date of occurrence. Results of the study found that 316 downhole source incidents were reported to the agency during this period of time, representing a total of 426 distinct sources of radioactivity lost downhole within the boundaries of the State of Texas. The sources lost were predominantly AmBe, accounting for 74 TBq of radioactivity at the time of loss, and Cs, accounting for 16.3 TBq of radioactivity. A longitudinal analysis of the data showed the average loss per active oil and gas rig in Texas (known as "rig count") at approximately 24 losses per 1,000 rigs. Specific geographic information was largely missing from many of the records, which prevented the geolocation of wells described to contain lost radioactive sources. As a result, most wells could only be located to the county level, and no comprehensive geographical information system (GIS) map could be accurately created from the data. However, when available, source location information was standardized to permit the characterization of the sources reported as lost. This effort produced the first dedicated compendium of lost downhole sources for the State of Texas and provides an important source of information for regulatory agencies. The ability to provide prompt information about the fate and location of sources of radioactivity is important to regulatory officials, given the recent concerns about radiation source inventory control in the post 9/11 world as it relates to the possible creation of radiological dispersal devices.

Background: Wood dust was designated as a human carcinogen based on increased sinus and nasal cancer rates among exposed workers. However, data on an association with lung cancer have been inconclusive., Methods: Self-reported wood dust exposure was compared between 1,368 lung cancer patients and 1,192 cancer-free adults, in a lung cancer case-control study. Epidemiological information was collected through a detailed personal interview., Results: Using several definitions of wood dust exposure we consistently observed statistically significant elevated adjusted risk estimates; for example, the adjusted odds ratio (OR) for combined wood dust related occupations and industries was 3.15 (95% confidence intervals (CI) 1.45-6.86) and for an overall summary exposure measure it was 1.60 (95% CI 1.19-2.14). The association was maintained when stratified by histopathological type. Among those exposed to cigarette smoke and wood dust, 21% of the cases were attributable to biologic interaction., Conclusions: Wood dust exposure is a potential risk factor for lung cancer., (Copyright (c) 2005 Wiley-Liss, Inc.)

The World Health Organization has identified a worldwide shortage of occupational health professionals, but evidence suggests that the work and education of these professionals vary across countries. This survey examined the professional development of occupational physicians, occupational nurses, industrial hygienists, and ergonomists in terms of practice competencies and academic curriculum. Of 89 countries that received the survey, 48 (54%) responded. Important differences in competencies and curricula were identified for all groups. More competencies were identified more frequently in developed countries. Academic programs existed more often in developed countries, but curriculum contents varied. The study provides a concrete reference point for discussion and development of competencies and curriculum.

Background: National estimates of occupational asthma (OA) in the United States are sparse., Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we analyzed associations between occupation and work-related asthma and work-related wheezing among U.S. workers., Results: This study identified several occupations that were at risk of developing work-related asthma and/or wheezing, with cleaners and equipment cleaners showing the highest risks. Other major occupations identified were farm and agriculture; entertainment; protective services; construction; mechanics and repairers; textile; fabricators and assemblers; other transportation and material moving occupations; freight, stock, and material movers; and motor vehicle operators. The population attributable risks for work-related asthma and work-related wheezing were 26% and 27%, respectively., Conclusions: This study adds evidence to the literature that identifies work-related asthma as an important public health problem. Several occupations are targeted for additional evaluation and study. Of particular interest are cleaners, which are being increasingly reported as a risk group for asthma. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace., (Copyright 2003 Wiley-Liss, Inc.)

The prevalence of asthma has been on the increase in the USA and worldwide. To understand the worsening epidemiological trends of asthma, this study analysed the data from the third National Health and Nutrition Examination Survey (NHANES III) to determine the prevalence and risk factors for asthma and wheezing among US adults. This analysis used data from 18,825 US adults aged > or = 20 yrs who had participated in the NHANES III project. After excluding subjects with physician-diagnosed emphysema, a total of 18,393 subjects were included in the final analysis. The prevalence of current asthma (asthma) was 4.5% and the prevalence of wheezing in the previous 12 months (wheezing) was 16.4%. Mexican-Americans exhibited the lowest prevalence of asthma when compared with other race/ethnic groups. Multiple logistic regression analysis showed that Mexican-Americans were less likely to report asthma when compared to non-Hispanic whites. Low education level, female sex, current and past smoking status, pet ownership, lifetime diagnosis of physician-diagnosed hay fever and obesity were all significantly associated with asthma and/or wheezing. No significant effect of indoor air pollutants, as derived from the use of household heating/cooking appliances, on asthma and wheezing was observed in this study. In conclusion, this study observed racial/ethnic differences in the prevalence of asthma and wheezing and identified several important risk factors that may contribute to development and/or exacerbation of asthma and wheezing. Contrary to earlier reports, the proxy measures of indoor air pollution used in this study were not found to be associated with increased risk of asthma and wheezing.

Objectives: To estimate the prevalence of work related asthma and work related wheezing in United States workers. To identify high risk industries that could be targeted for future intervention. To determine the population attributable risk of work related asthma and work related wheezing., Methods: The third national health and nutrition examination survey, 1988-1994 (NHANES III) was analyzed to determine the prevalence of work related asthma and wheezing and to identify initially defined industries at risk among United States workers aged 20 and older. Separate logistic models were developed with work related asthma and work related wheezing as outcomes. Work related asthma was defined as affirmative response to questions on self reported physician diagnosed asthma and work related symptoms of rhinitis, conjunctivitis, and asthma. Work related wheezing was defined as affirmative response to questions on self reported wheezing or whistling in the chest in the previous 12 months and work related symptoms of rhinitis, conjunctivitis, and asthma. All analyses were adjusted for age, sex, smoking, and atopy., Results: The prevalence of work related asthma was 3.70% (95% confidence interval (95% CI) 2.88 to 4.52) and the prevalence of work related wheezing was 11.46% (95% CI 9.87 to 13.05). The main industries identified at risk of work related asthma and wheeze included the entertainment industry; agriculture, forestry, and fishing; construction; electrical machinery; repair services; and lodging places. The population attributable risk for work related asthma was 36.5% and work related wheezing was 28.5%., Conclusions: The findings provide impetus for further research and actions by public health professionals which prioritise occupational asthma on the public health agenda. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace.

Background: As observed in tobacco-associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos-associated carcinogenesis., Methods: RFLP-PCR analysis identified the MPO genotypes in 375 Caucasian lung cancer cases and 378 matched controls. An epidemiological interview elicited detailed information regarding smoking history and occupational history and exposures., Results: Asbestos exposure was associated with a significantly elevated risk estimate (OR = 1.45; 95% CI 1.04-2.02). On stratified analysis, we found the MPO genotypes modified the effect of asbestos exposure on lung cancer risk. Specifically, G/G carriers who were exposed to asbestos had an odds ratio (OR) of 1.72 (95% CI; 1.09-2.66), while A-allele carriers (G/A + A/A) exposed to asbestos exhibited a reduced OR of 0.89 (95% CI; 0.56-1.44). The OR was further reduced to 0.73 (0.49-1.06) for A-allele carriers not exposed to asbestos. A similar trend was observed for the joint effects between the MPO genotypes and pack-years smoking. Next, all three risk factors (MPO genotypes, asbestos exposure, and smoking) were analyzed simultaneously for joint effects. Heavy smokers with the G/G genotype and a history of asbestos exposure demonstrated a statistically significant elevated risk estimate (OR = 2.19; 95% CI 1.16-4.11), while the A-allele carriers with the same exposure profile were at a lower risk for lung cancer (OR = 1.18; 95% CI 0.58-2.38). The A-allele genotypes demonstrated similar protective effects for the other three exposure profiles., Conclusions: For a similar level of exposure to established carcinogens, individuals with the MPO A-allele genotypes appear to have a reduced risk of lung cancer., (Copyright 2002 Wiley-Liss, Inc.)

Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G-->A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.

As part of the Partners in School Asthma Management Program, environmental data were collected from 385 rooms in 60 elementary schools in southeast Texas, using an Environmental Observation Checklist and a Q-TRAK Indoor Air Quality Monitor. Dust samples for allergen analysis were collected from floors, carpets, and area rugs in 80 classrooms in a subset of 20 schools. CO2 levels > 1,000 ppm were found in 86% of rooms; 69% had indoor humidity above recommended levels. Der p I dust mite allergen levels > 2,000 ng/g were present in 20% of rooms, but only 2.5% of rooms had Der f I mite allergen levels exceeding recommended tolerances. Detectable levels of cockroach allergen (Bla g II) were found in all schools (median 5.5 ng/g), with 10% of rooms over the recommended threshold. Almost two-thirds of classrooms had mold spore counts > 10,000 col/g (median, 14,400 col/g; range, 2,000-52,000 col/g).

Sick Building Syndrome remains a prevalent problem with patient complaints similar to typical allergy symptoms. Unlike household allergens typically found in domestic reservoirs, the allergen from a common fungus like Aspergillus fumigatus (i.e., Asp f 1) is conceivably widespread in the work environment. This project surveyed airborne levels of the Asp f 1 allergen in office and non-industrial occupational environments, as well as the dust reservoirs of A. fumigatus believed to be responsible for those levels. Airborne and bulk dust samples were collected, extracted, and assayed for Asp f 1. Concurrently, bulk dusts collected from the same locations were selectively cultured for A. fumigatus, and mesophilic fungi and bacteria. Samples were collected during both wet and dry climatological conditions from paired wet and dry building locations to examine the possibility of Asp f 1 increases due to fungal growth blooms. Very low levels of Asp f 1 were detected but only in the airborne samples (2/120 positive samples, with 3.6 ng/m3 and 1.8 ng/m3; LOD < 1.2 ng/m3). No dust samples showed even detectable traces of the allergen (LOD = 5 ng/g dust). Although A. fumigatus counts from dusts fluctuated significantly with exterior moisture events, analysis of wet versus dry period samples showed no differences in Asp f 1 levels. These results indicate that even in the presence of measurable fungal concentrations, background levels of Asp f 1 are low. Nonindustrial office buildings devoid of indoor air quality issues were not observed to have significant levels of the Asp f 1 allergen in the geographical region studied.

A method is presented which links on-site electromagnetic field monitoring data with pre-existing work history data. The linkage is used to estimate cumulative and average annualized magnetic field exposure for a case-control study. On-site electromagnetic field monitoring data for 1,966 volunteer utility employees, at 59 sites in the United States and three other countries, were obtained from a large project (the EMDEX project) designed to collect, analyze, and document 60-Hz electric and magnetic field exposures for a diverse population. These data represent 9 primary work environments, and 16 job classification categories, amounting to 144 unique job categories which were consolidated using the job-exposure matrix presented into 282 three-digit Dictionary of Occupational Title (DOT) codes. The DOT code categories were then linked to lifetime occupational histories from a case-control study of leukemia. The method may be extended to link additional job titles with monitoring information. Job titles linked with electromagnetic field monitoring information provide more specific estimates of exposure intensity than previous ordinal estimates of exposure. Therefore, estimates of cumulative electromagnetic field exposure are achievable, as well as high and low level exposure estimates.