Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-23 (of 23 Records) |
Query Trace: Roach K [original query] |
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Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.
Roach KA , Kodali V , Shoeb M , Meighan T , Kashon M , Stone S , McKinney W , Erdely A , Zeidler-Erdely PC , Roberts JR , Antonini JM . Toxicol Appl Pharmacol 2023 464 116436 The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses. |
A comprehensive summary of disease variants implicated in metal allergy
Roach K , Roberts J . J Toxicol Environ Health B Crit Rev 2022 25 (6) 1-63 Allergic disease represents one of the most prominent global public health crises of the 21(st) century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy - including allergic contact dermatitis - are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed - from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described.Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet. |
Overcoming Barriers to Successful Climate and Health Adaptation Practice: Notes from the Field.
Mallen E , Joseph HA , McLaughlin M , English DQ , Olmedo C , Roach M , Tirdea C , Vargo J , Wolff M , York E . Int J Environ Res Public Health 2022 19 (12) State and local public health agencies are at the forefront of planning and responding to the health challenges of climate hazards but face substantial barriers to effective climate and health adaptation amidst concurrent environmental and public health crises. To ensure successful adaptation, it is necessary to understand and overcome these barriers. The U.S. Centers for Disease Control and Prevention Climate-Ready States and Cities Initiative (CRSCI) provides funding to state and local health departments to anticipate and respond to health impacts from climate change using the Building Resilience Against Climate Effects (BRACE) framework. This paper explores the barriers to and enablers of successful adaptation projects among BRACE West CRSCI grantees, including Arizona, California, Oregon, and the city and county of San Francisco. The barriers included competing demands such as the COVID-19 pandemic, dependence on partners with similar challenges, staff and leadership turnover, uncertain and complex impacts on at-risk populations, and inadequate resources. The enablers included effective partnerships, leadership support, dedicated and skilled internal staff, and policy windows enabling institutional change and reprioritization. These findings highlight effective strategies in the field that state and local health departments may use to anticipate potential barriers and establish their work in an environment conducive to successful adaptation. |
Extreme heat exposure: Access and barriers to cooling centers - Maricopa and Yuma Counties, Arizona, 2010-2020
Mallen E , Roach M , Fox L , Gillespie E , Watkins L , Hondula DM , Vaidyanathan A , Manangan A , Perkins AN , Schramm PJ . MMWR Morb Mortal Wkly Rep 2022 71 (24) 781-785 Extreme heat exposure increases the risk for heat-related illnesses (HRIs) and deaths, and comprehensive strategies to prevent HRIs are increasingly important in a warming climate (1). An estimated 702 HRI-associated deaths and 67,512 HRI-associated emergency department visits occur in the United States each year (2,3). In 2020, Phoenix and Yuma, Arizona, experienced a record 145 and 148 days, respectively, of temperatures >100°F (37.8°C), and a record 522 heat-related deaths occurred in the state. HRIs are preventable through individual and community-based strategies*(,)(†); cooling centers,(§) typically air-conditioned or cooled buildings designated as sites to provide respite and safety during extreme heat, have been established in Maricopa and Yuma counties to reduce HRIs among at-risk populations, such as older adults. This analysis examined trends in HRIs by age during 2010-2020 for Maricopa and Yuma counties and data from a survey of older adults related to cooling center availability and use in Yuma County during 2018-2019. Data from CDC's Social Vulnerability Index (SVI) were also used to overlay cooling center locations with SVI scores. During 2010-2020, heat days, defined as days with an excessive heat warning issued by the National Weather Service Phoenix Office,(¶) for any part of Maricopa and Yuma counties (4), increased in both Maricopa County (1.18 days per year) and Yuma County (1.71 days per year) on average. Adults aged ≥65 years had higher rates of HRI hospitalization compared with those aged <65 years. In a survey of 39 adults aged ≥65 years in Yuma County, 44% reported recent HRI symptoms, and 18% reported electricity cost always or sometimes constrained their use of air conditioning. Barriers to cooling center access among older adults include awareness of location and transportation. Collaboration among diverse community sectors and health profession education programs is important to better prepare for rising heat exposure and HRIs. States and communities can implement adaptation and evaluation strategies to mitigate and assess heat risk, such as the use of cooling centers to protect communities disproportionately affected by HRI during periods of high temperatures. |
Comparison of product safety data sheet ingredient lists with skin irritants and sensitizers present in a convenience sample of light-curing resins used in additive manufacturing
Bowers LN , Ranpara AC , Roach KA , Knepp AK , Arnold ED , Stefaniak AB , Virji MA . Regul Toxicol Pharmacol 2022 133 105198 Material jetting and vat photopolymerization additive manufacturing (AM) processes use liquid resins to build objects. These resins can contain skin irritants and/or sensitizers but product safety data sheets (SDSs) might not declare all ingredients. We characterized elemental and organic skin irritants and sensitizers present in 39 commercial products; evaluated the influence of resin manufacturer, system, color, and AM process type on the presence of irritants and sensitizers; and compared product SDSs to results. Among all products, analyses identified 23 irritant elements, 54 irritant organic substances, 22 sensitizing elements, and 23 sensitizing organic substances; SDSs listed 3, 9, 4, and 6 of these ingredients, respectively. Per product, the number and total mass (an indicator of potential dermal loading) of ingredients varied: five to 17 irritant elements (8.32-4756.65mg/kg), one to 17 irritant organics (3273 to 356,000mg/kg), four to 17 sensitizing elements (8.27-4755.63mg/kg), and one to seven sensitizing organics (15-382,170mg/kg). Median numbers and concentrations of irritants and sensitizers were significantly influenced by resin system and AM process type. The presence of undeclared irritants and sensitizers in these resins supports the need for more complete information on product SDSs for comprehensive dermal risk assessments. |
Welding fume inhalation exposure and high-fat diet change lipid homeostasis in rat liver
Boyce GR , Shoeb M , Kodali V , Meighan TG , Roach KA , McKinney W , Stone S , Powell MJ , Roberts JR , Zeidler-Erdely PC , Erdely A , Antonini JM . Toxicol Rep 2020 7 1350-1355 It is estimated that greater than 1 million workers are exposed to welding fume (WF) by inhalation daily. The potentially toxic metals found in WF are known to cause multiple adverse pulmonary and systemic effects, including cardiovascular disease, and these metals have also been shown to translocate to the liver. This occupational exposure combined with a high fat (HF) Western diet, which has been shown to cause hyperlipidemia and non-alcoholic fatty liver disease (NAFLD), has the potential to cause significant mixed exposure metabolic changes in the liver. The goal of this study was to use matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to analyze the spatial distribution and abundance changes of lipid species in Sprague Dawley rat liver maintained on a HF diet combined with WF inhalation. The results of the MALDI-IMS analysis revealed unique hepatic lipid profiles for each treatment group. The HF diet group had significantly increased abundance of triglycerides and phosphatidylinositol lipids, as well as decreased lysophosphatidic lipids and cardiolipin. Ceramide-1-phosphate was found at higher abundance in the regular (REG) diet WF-exposed group which has been shown to regulate the eicosanoid pathway involved in pro-inflammatory response. The results of this study showed that the combined effects of WF inhalation and a HF diet significantly altered the hepatic lipidome. Additionally, pulmonary exposure to WF alone increased lipid markers of inflammation. |
Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold
Roach KA , Anderson SE , Stefaniak AB , Shane HL , Boyce GR , Roberts JR . Nanotoxicology 2020 14 (8) 1-22 Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl(3)) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl(3) then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group - simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure. |
Toxicity evaluation following pulmonary exposure to an as-manufactured dispersed boron nitride nanotube (BNNT) material in vivo
Xin X , Barger M , Roach KA , Bowers L , Stefaniak AB , Kodali V , Glassford E , Dunn KL , Dunn KH , Wolfarth M , Friend S , Leonard SS , Kashon M , Porter DW , Erdely A , Roberts JR . NanoImpact 2020 19 Boron nitride nanotubes (BNNT) are multi-walled nanotubes composed of hexagonal B[sbnd]N bonds and possess many unique physical and chemical properties, creating a rapidly expanding market for this newly emerging nanomaterial which is still primarily in the research and development stage. The shape and high aspect ratio give rise to concern for the potential toxicity that may be associated with pulmonary exposure, especially in an occupational setting. The goal of this study was to assess lung toxicity using an in vivo time course model. The sample was manufactured to be 5 nm wide and up to 200 μm long, with ~50% purity covalently bound with hexagonal boron nitride (hBN) in the sample. Following preparation for in vivo studies, sonication of the material disrupted the longer tubes in the complex and the size distribution in dispersion medium (DM) of the structures was 13–23 nm in diameter and 0.6–1.6 μm in length. Male C57BL/6 J mice were exposed to 4 or 40 μg of BNNT or DM (vehicle control) by a single oropharyngeal aspiration. Pulmonary and systemic toxicity were investigated at 4 h, 1 d, 7 d, 1 mo and 2 mo post-exposure. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation (neutrophil influx) and cytotoxicity (lactate dehydrogenase activity) occurred at early time points and peaked at 7 d post-exposure in the high dose group. Histopathological analysis showed a minimal level of inflammatory cell infiltration in the high dose group with resolution over time and no fibrosis, and lung clearance analysis showed ~50% of the material cleared over the time course. The expression of inflammatory- and acute phase response-associated genes in the lung and liver were significantly increased by the high dose at 4 h and 1 d post-exposure. The increases in lung gene expression of Cxcl2, Ccl2, Il6, Ccl22, Ccl11, and Spp1 were significant up to 2 mo but decreased with time. The low dose exposure did not result in significant changes in any toxicological parameters measured. In summary, the BNNT-hBN sample used in this study caused acute pulmonary inflammation and injury at the higher dose, which peaked by 7 d post-exposure and showed resolution over time. Further studies are needed to determine if physicochemical properties and purity will impact the toxicity profile of BNNT and to investigate the underlying mechanisms of BNNT toxicity. |
Effect of a high fat diet and occupational exposure in different rat strains on lung and systemic responses: examination of the exposome in an animal model
Antonini JM , Kodali V , Shoeb M , Kashon M , Roach KA , Boyce G , Meighan T , Stone S , McKinney W , Boots T , Roberts JR , Zeidler-Erdely PC , Erdely A . Toxicol Sci 2019 174 (1) 100-111 The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds [Fischer-344, Sprague-Dawley, Brown-Norway] maintained on a regular (REG) or high fat (HF) diet for 24 wk. At wk 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 x 3 hr/d x 4 d/wk x 5 wk) or air until wk 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24 wk period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 wk to assess general health indices. Depending on animal strain, WF exposure and HF diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain. |
Surface area- and mass-based comparison of fine and ultrafine nickel oxide lung toxicity and augmentation of allergic response in an ovalbumin asthma model
Roach KA , Anderson SE , Stefaniak AB , Shane HL , Kodali V , Kashon M , Roberts JR . Inhal Toxicol 2019 31 (8) 1-26 Background: The correlation of physico-chemical properties with mechanisms of toxicity has been proposed as an approach to predict the toxic potential of the vast number of emerging nanomaterials. Although relationships have been established between properties and the acute pulmonary inflammation induced by nanomaterials, properties' effects on other responses, such as exacerbation of respiratory allergy, have been less frequently explored.Methods: In this study, the role of nickel oxide (NiO) physico-chemical properties in the modulation of ovalbumin (OVA) allergy was examined in a murine model. Results: 181 nm fine (NiO-F) and 42 nm ultrafine (NiO-UF) particles were characterized and incorporated into a time course study where measured markers of pulmonary injury and inflammation were associated with NiO particle surface area. In the OVA model, exposure to NiO, irrespective of any metric was associated with elevated circulating total IgE levels. Serum and lung cytokine levels were similar with respect to NiO surface area. The lower surface area was associated with an enhanced Th2 profile, whereas the higher surface area was associated with a Th1-dominant profile. Surface area-normalized groups also exhibited similar alterations in OVA-specific IgE levels and lung neutrophil number. However, lung eosinophil number and allergen challenge-induced alterations in lung function related more to particle size, wherein NiO-F was associated with an increased enhanced pause response and NiO-UF was associated with increased lung eosinophil burden.Conclusions: Collectively, these findings suggest that although NiO surface area correlates best with acute pulmonary injury and inflammation following respiratory exposure, other physico-chemical properties may contribute to the modulation of immune responses in the lung. |
A possible relationship between telomere length and markers of neurodegeneration in rat brain after welding fume inhalation exposure
Shoeb M , Mustafa GM , Kodali VK , Smith K , Roach KA , Boyce G , Meighan T , Roberts JR , Erdely A , Antonini JM . Environ Res 2019 180 108900 Inhalation of welding fume (WF) can result in the deposition of toxic metals, such as manganese (Mn), in the brain and may cause neurological changes in exposed workers. Alterations in telomere length are indicative of cellular aging and, possibly, neurodegeneration. Here, we investigated the effect of WF inhalation on telomere length and markers of neurodegeneration in whole brain tissue in rats. Male Fischer-344 (F-344) rats were exposed by inhalation to stainless steel WF (20mg/m(3) x 3h/d x 4d/wk x 5wk) or filtered air (control). Telomere length, DNA-methylation, gene expression of Trf1, Trf2, ATM, and APP, protein expression of p-Tau, alpha-synuclein, and presenilin 1 and 2 were assessed in whole brain tissue at 12wk after WF exposure ended. Results suggest that WF inhalation increased telomere length without affecting telomerase in whole brain. Moreover, we observed that components of the shelterin complex, Trf1 and Trf2, play an important role in telomere end protection, and their regulation may be responsible for the increase in telomere length. In addition, expression of different neurodegeneration markers, such as p-Tau, presenilin 1-2 and alpha-synuclein proteins, were increased in brain tissue from the WF-exposed rats as compared to control. These findings suggest a possible correlation between epigenetic modifications, telomere length alteration, and neurodegeneration because of the presence of factors in serum after WF exposure that may cause extra-pulmonary effects as well as the translocation of potentially neurotoxic metals associated with WF to the central nervous system (CNS). Further studies are needed to investigate the brain region specificity and temporal response of these effects. |
Exposure to graphene nanoparticles induces changes in measures of vascular/renal function in a load and form-dependent manner in mice
Krajnak K , Waugh S , Stefaniak A , Schwegler-Berry D , Roach K , Barger M , Roberts J . J Toxicol Environ Health A 2019 82 (12) 1-16 Graphenes isolated from crystalline graphite are used in several industries. Employees working in the production of graphenes may be at risk of developing respiratory problems attributed to inhalation or contact with particulate matter (PM). However, graphene nanoparticles might also enter the circulation and accumulate in other organs. The aim of this study was to examine how different forms of graphene affect peripheral vascular functions, generation of reactive oxygen species (ROS) and changes in gene expression that may be indicative of cardiovascular and/or renal dysfunction. In the first investigation, different doses of graphene nanoplatelets were administered to mice via oropharyngeal aspiration. These effects were compared to those of dispersion medium (DM) and carbon black (CB). Gene expression alterations were observed in the heart for CB and graphene; however, only CB produced changes in peripheral vascular function. In the second study, oxidized forms of graphene were administered. Both oxidized forms increased the sensitivity of peripheral blood vessels to adrenoreceptor-mediated vasoconstriction and induced changes in ROS levels in the heart. Based upon the results of these investigations, exposure to graphene nanoparticles produced physiological and alterations in ROS and gene expression that may lead to cardiovascular dysfunction. Evidence indicates that the effects of these particles may be dependent upon dose and graphene form to which an individual may be exposed to. |
Metal nanomaterials: Immune effects and implications of physicochemical properties on sensitization, elicitation, and exacerbation of allergic disease
Roach KA , Stefaniak AB , Roberts JR . J Immunotoxicol 2019 16 (1) 87-124 The recent surge in incorporation of metallic and metal oxide nanomaterials into consumer products and their corresponding use in occupational settings have raised concerns over the potential for metals to induce size-specific adverse toxicological effects. Although nano-metals have been shown to induce greater lung injury and inflammation than their larger metal counterparts, their size-related effects on the immune system and allergic disease remain largely unknown. This knowledge gap is particularly concerning since metals are historically recognized as common inducers of allergic contact dermatitis, occupational asthma, and allergic adjuvancy. The investigation into the potential for adverse immune effects following exposure to metal nanomaterials is becoming an area of scientific interest since these characteristically lightweight materials are easily aerosolized and inhaled, and their small size may allow for penetration of the skin, which may promote unique size-specific immune effects with implications for allergic disease. Additionally, alterations in physicochemical properties of metals in the nano-scale greatly influence their interactions with components of biological systems, potentially leading to implications for inducing or exacerbating allergic disease. Although some research has been directed toward addressing these concerns, many aspects of metal nanomaterial-induced immune effects remain unclear. Overall, more scientific knowledge exists in regards to the potential for metal nanomaterials to exacerbate allergic disease than to their potential to induce allergic disease. Furthermore, effects of metal nanomaterial exposure on respiratory allergy have been more thoroughly-characterized than their potential influence on dermal allergy. Current knowledge regarding metal nanomaterials and their potential to induce/exacerbate dermal and respiratory allergy are summarized in this review. In addition, an examination of several remaining knowledge gaps and considerations for future studies is provided. |
Effect of Age, High-Fat Diet, and Rat Strain on Serum Biomarkers and Telomere Length and Global DNA Methylation in Peripheral Blood Mononuclear Cells.
Antonini JM , Kodali V , Meighan TG , Roach KA , Roberts JR , Salmen R , Boyce GR , Zeidler-Erdely PC , Kashon M , Erdely A , Shoeb M . Sci Rep 2019 9 (1) 1996 The objective of the current study was to determine if age, diet, and genetic disposition (animal strain) in an animal model had early effects on specific molecular markers in circulating peripheral blood mononuclear cells (PBMCs). Three strains [Sprague-Dawley (SD), Fischer 344 (F344), and Brown-Norway (BN)] of male rats were maintained on a high-fat (HF) or regular diet. Blood was collected at 4, 12, and 24 wk to assess chemistry and to recover PBMCs. Triglycerides and body weight gain increased at all time points in the HF diet group for each strain. Telomere length in PBMCs decreased in the HF diet group compared to the regular diet group up to 24 wk in all strains. Telomere length decreased in PBMCs at 24 wk compared to baseline in all strains, indicating an age-related effect. These findings highlight that diet and age cause changes in PBMCs recovered from different strains of rats. The next tier of studies will examine the contribution of an occupational exposure (e.g., welding fume inhalation) in combination with diet, age, and strain, to assess changes in the molecular responses of isolated PBMCs. In addition, studies involving lifestyle exposure (e.g., tobacco smoke) are in the planning stages and will assess the long-term effects of exposure in our animal model. |
Initiation of Pulmonary Fibrosis after Silica Inhalation in Rats is linked with Dysfunctional Shelterin Complex and DNA Damage Response.
Shoeb M , Mustafa GM , Joseph P , Umbright C , Kodali V , Roach KA , Meighan T , Roberts JR , Erdely A , Antonini JM . Sci Rep 2019 9 (1) 471 Occupational exposure to silica has been observed to cause pulmonary fibrosis and lung cancer through complex mechanisms. Telomeres, the nucleoprotein structures with repetitive (TTAGGG) sequences at the end of chromosomes, are a molecular "clock of life", and alterations are associated with chronic disease. The shelterin complex (POT1, TRF1, TRF2, Tin2, Rap1, and POT1 and TPP1) plays an important role in maintaining telomere length and integrity, and any alteration in telomeres may activate DNA damage response (DDR) machinery resulting in telomere attrition. The goal of this study was to assess the effect of silica exposure on the regulation of the shelterin complex in an animal model. Male Fisher 344 rats were exposed by inhalation to Min-U-Sil 5 silica for 3, 6, or 12 wk at a concentration of 15 mg/m(3) for 6 hr/d for 5 consecutive d/wk. Expression of shelterin complex genes was assessed in the lungs at 16 hr after the end of each exposure. Also, the relationship between increased DNA damage protein (gammaH2AX) and expression of silica-induced fibrotic marker, alphaSMA, was evaluated. Our findings reveal new information about the dysregulation of shelterin complex after silica inhalation in rats, and how this pathway may lead to the initiation of silica-induced pulmonary fibrosis. |
Working Time Society consensus statements: Regulatory approaches to reduce risks associated with shift work-a global comparison
Gartner J , Rosa RR , Roach G , Kubo T , Takahashi M . Ind Health 2019 57 (2) 245-263 A large number of workers worldwide engage in shift work that can have significant influences upon the quality of working life. For most jurisdictions, setting and enforcing appropriate policies, regulations, and rules around shift work is considered essential to (a) prevent potentially negative consequences of shift work and (b) to improve worker health and well-being. However, the best ways to do this are often highly contested theoretical spaces and often culturally and historically bound. In this paper, we examine the regulatory approaches to regulating shift work in four different regions: Europe, North America, Australasia, and East Asia (Japan, China, and Korea). Despite the fact that social and cultural factors vary considerably across the regions, comparing regulatory frameworks and initiatives in one region can be instructive. Different approaches can minimally provide a contrast to stimulate discussion about custom and practice and, potentially, help us to develop new and innovative models to improve worker well-being and organizational productivity simultaneously. In this paper, our goal is not to develop or even advocate a "perfect" sets of regulations. Rather, it is to compare and contrast the diversity and changing landscape of current regulatory practices and to help organizations and regulators understand the costs and benefits of different approaches. For example, in recent years, many western countries have seen a shift away from prescriptive regulation toward more risk-based approaches. Advocates and critics vary considerably in what drove these changes and the benefit-cost analyses associated with their introduction. By understanding the different ways in which shift work can be regulated, it may be possible to learn from others and to better promote healthier and safer environments for shift-working individuals and workplaces. |
Better together: Developmental screening and monitoring best identify children who need early intervention
Barger B , Rice C , Wolf R , Roach A . Disabil Health J 2018 11 (3) 420-426 BACKGROUND: Widely recommended developmental surveillance methods include developmental monitoring (DM) and development screening (DS). Much research has been done on DS, but very little research has compared the effectiveness of DM and DS together. OBJECTIVES: To investigate the relationship between DM and DS in Part C early intervention (EI) service receipt. METHODS: Authors used data from the 2007/2008 and 2011/2012 National Survey of Children's Health (NSCH). Authors report the prevalence of children aged 10 months to 3 years who received (a) DM only, (b) DS only, (c) both DM and DS, and (c) no DM or DS across survey years. Authors compare the odds of EI receipt across these groups. RESULTS: During both periods, estimated EI receipt prevalence was higher for children receiving both DM and DS (8.38% in 2007/2008; 6.47% in 2011/2012) compared to children receiving no DM or DS (1.31% in 2007/2008; 1.92% in 2011/2012), DM alone (2.74% in 2007/2008; 2.70% in 2011/2012), or DS alone (3.59% in 2007/2008; 3.09% in 2011/2012) (for both time frames, p<.05). From 2007/2008 to 2011/2012, the proportion of children receiving DS only and both DM and DS increased, while children receiving DM only and no DM or DS decreased. CONCLUSIONS: Children receiving DM and DS together were more likely to receive EI compared to children receiving DM alone, DS alone, or neither DM nor DS. These findings support the AAP recommendations indicating that DM and DS are complementary strategies for improving early identification and linkage to EI for young children. |
Sustained reduction in Chlamydia infections following a school-based screening: Detroit, 2010-2015
Dunville R , Peterson A , Liddon N , Roach M , Coleman K , Dittus P . Am J Public Health 2017 108 (2) e1-e3 We describe school-based screening events in four Detroit, Michigan public high schools. To examine trends, we analyzed Chlamydia trachomatis data from 2010 to 2015. Prevalence of C. trachomatis decreased significantly (P < .01): from 10.24% to 6.27%. Future school-based screening events may bring about similar results if the program is instituted in a high-prevalence area and can achieve high student participation. (Am J Public Health. Published online ahead of print December 21, 2017: e1-e3. doi:10.2105/AJPH.2017.304163). |
Acute in vitro and in vivo toxicity of a commercial grade boron nitride nanotube mixture
Kodali VK , Roberts JR , Shoeb M , Wolfarth MG , Bishop L , Eye T , Barger M , Roach KA , Friend S , Schwegler-Berry D , Chen BT , Stefaniak A , Jordan KC , Whitney RR , Porter DW , Erdely AD . Nanotoxicology 2017 11 (8) 1-19 Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of approximately 50-60% BNNTs, and approximately 40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 microg/ml and C57BL/6 J male mice were treated with 40 microg of BNNT-M for in vitro and in vivo studies, respectively. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1beta and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein production when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The observed results demonstrated acute inflammation and toxicity in vitro and in vivo following exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation. |
Pulmonary toxicity following acute coexposures to diesel particulate matter and alpha-quartz crystalline silica in the Sprague-Dawley rat
Farris BY , Antonini JM , Fedan JS , Mercer RR , Roach KA , Chen BT , Schwegler-Berry D , Kashon ML , Barger MW , Roberts JR . Inhal Toxicol 2017 29 (7) 1-18 The effects of acute pulmonary coexposures to silica and diesel particulate matter (DPM), which may occur in various mining operations, were investigated in vivo. Rats were exposed by intratracheal instillation (IT) to silica (50 or 233 microg), DPM (7.89 or 50 microg) or silica and DPM combined in phosphate-buffered saline (PBS) or to PBS alone (control). At one day, one week, one month, two months and three months postexposure bronchoalveolar lavage and histopathology were performed to assess lung injury, inflammation and immune response. While higher doses of silica caused inflammation and injury at all time points, DPM exposure alone did not. DPM (50 microg) combined with silica (233 microg) increased inflammation at one week and one-month postexposure and caused an increase in the incidence of fibrosis at one month compared with exposure to silica alone. To assess susceptibility to lung infection following coexposure, rats were exposed by IT to 233 microg silica, 50 microg DPM, a combination of the two or PBS control one week before intratracheal inoculation with 5 x 105 Listeria monocytogenes. At 1, 3, 5, 7 and 14 days following infection, pulmonary immune response and bacterial clearance from the lung were evaluated. Coexposure to DPM and silica did not alter bacterial clearance from the lung compared to control. Although DPM and silica coexposure did not alter pulmonary susceptibility to infection in this model, the study showed that noninflammatory doses of DPM had the capacity to increase silica-induced lung injury, inflammation and onset/incidence of fibrosis. |
Modeled changes in US sodium intake from reducing sodium concentrations of commercially processed and prepared foods to meet voluntary standards established in North America: NHANES
Cogswell ME , Patel SM , Yuan K , Gillespie C , Juan W , Curtis CJ , Vigneault M , Clapp J , Roach P , Moshfegh A , Ahuja J , Pehrsson P , Brookmire L , Merritt R . Am J Clin Nutr 2017 106 (2) 530-540 Background: Approximately 2 in 3 US adults have prehypertension or hypertension that increases their risk of cardiovascular disease. Reducing sodium intake can decrease blood pressure and prevent hypertension. Approximately 9 in 10 Americans consume excess sodium (≥2300 mg/d). Voluntary sodium standards for commercially processed and prepared foods were established in North America, but their impact on sodium intake is unclear.Objective: We modelled the potential impact on US sodium intake of applying voluntary sodium standards for foods.Design: We used NHANES 2007-2010 data for 17,933 participants aged ≥1 y to model predicted US daily mean sodium intake and the prevalence of excess sodium intake with the use of the standards of the New York City's National Salt Reduction Initiative (NSRI) and Health Canada for commercially processed and prepared foods. The Food and Nutrient Database for Dietary Studies food codes corresponding to foods reported by NHANES participants were matched to NSRI and Health Canada food categories, and the published sales-weighted mean percent reductions were applied.Results: The US population aged ≥1 y could have reduced their usual daily mean sodium intake of 3417 mg by 698 mg (95% CI: 683, 714 mg) by applying NSRI 2014 targets and by 615 mg (95% CI: 597, 634 mg) by applying Health Canada's 2016 benchmarks. Significant reductions could have occurred, regardless of age, sex, race/ethnicity, income, education, or hypertension status, up to a mean reduction in sodium intake of 850 mg/d in men aged ≥19 y by applying NSRI targets. The proportion of adults aged ≥19 y who consume ≥2300 mg/d would decline from 88% (95% CI: 86%, 91%) to 71% (95% CI: 68%, 73%) by applying NSRI targets and to 74% (95% CI: 71%, 76%) by applying Health Canada benchmarks.Conclusion: If established sodium standards are applied to commercially processed and prepared foods, a significant reduction of US sodium intake could occur. |
Assessing adaptation strategies for extreme heat: A public health evaluation of cooling centers in Maricopa County, Arizona
Berisha V , Hondula D , Roach M , White JR , McKinney B , Bentz D , Mohamed A , Uebelherr J , Goodin K . Weather Clim Soc 2017 9 (1) 71-80 Preventing heat-associated morbidity and mortality is a public health priority in Maricopa County, Arizona (United States). The objective of this project was to evaluate Maricopa County cooling centers and gain insight into their capacity to provide relief for the public during extreme heat events. During the summer of 2014, 53 cooling centers were evaluated to assess facility and visitor characteristics. Maricopa County staff collected data by directly observing daily operations and by surveying managers and visitors. The cooling centers in Maricopa County were often housed within community, senior, or religious centers, which offered various services for at least 1500 individuals daily. Many visitors were unemployed and/or homeless. Many learned about a cooling center by word of mouth or by having seen the cooling center's location. The cooling centers provide a valuable service and reach some of the region's most vulnerable populations. This project is among the first to systematically evaluate cooling centers from a public health perspective and provides helpful insight to community leaders who are implementing or improving their own network of cooling centers. |
Range of motion measurements: reference values and a database for comparison studies
Soucie JM , Wang C , Forsyth A , Funk S , Denny M , Roach KE , Boone D . Haemophilia 2010 17 (3) 500-7 SUMMARY: Many diseases and injuries can impair joint mobility. Normal reference values are needed to determine extent of impairment to assess and monitor joint motion. There is very little published data describing normal joint range of motion (ROM) for healthy men and women across a wide span of ages. We enrolled male and female subjects aged between 2 and 69 years who were free from conditions that could potentially limit joint mobility for the study. Nine licensed physical therapists used universal goniometers to determine passive joint motion bilaterally of elbow flexion, extension, supination and pronation, shoulder flexion, hip flexion and extension, knee flexion and extension, and ankle dorsiflexion and plantarflexion. Descriptive statistics were calculated for male and female subjects in four age groups: 2-8, 9-19, 20-44 and 45-69 years. Joint ROM measurements were obtained on a total of 674 (53.6% female) healthy, normal subjects aged 2-69 years. Female subjects had greater joint mobility in all age groups in nearly all joints and the gender difference was most obvious in measures of ankle plantarflexion, elbow pronation and supination. Range of motion average values for all joints decreased with advancing age for both men and women and, in most cases, were significantly different than most commonly used normative values. Our study of ROM measurements taken by trained physical therapists on a large sample of healthy individuals revealed significant gender- and age-related variation that may be an important consideration in patient assessment. |
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