Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Trainor T[original query] |
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Lung toxicity profile of inhaled copper-nickel welding fume in A/J mice
Zeidler-Erdely PC , Erdely A , Kodali V , Andrews R , Antonini J , Trainor-DeArmitt T , Salmen R , Battelli L , Grose L , Kashon M , Service S , McKinney W , Stone S , Falcone L . Inhal Toxicol 2022 34 1-12 Objective: Stainless steel welding creates fumes rich in carcinogenic metals such as chromium (Cr). Welding consumables devoid of Cr are being produced in an attempt to limit worker exposures to toxic and carcinogenic metals. The study objective was to characterize a copper-nickel (Cu-Ni) fume generated using gas metal arc welding (GMAW) and determine the pulmonary deposition and toxicity of the fume in mice exposed by inhalation. Materials and Methods: Male A/J mice (6-8 weeks of age) were exposed to air or Cu-Ni welding fumes for 2 (low deposition) or 4 (high deposition) hours/day for 10 days. Mice were sacrificed, and bronchoalveolar lavage (BAL), macrophage function, and histopathological analyses were performed at different timepoints post-exposure to evaluate resolution. Results and Discussion: Characterization of the fume indicated that most of the particles were between 0.1 and 1 µm in diameter, with a mass median aerodynamic diameter of 0.43 µm. Metal content of the fume was Cu (∼76%) and Ni (∼12%). Post-exposure, BAL macrophages had a reduced ability to phagocytose E. coli, and lung cytotoxicity was evident and significant (>12%-19% fold change). Loss of body weight was also significant at the early timepoints. Lung inflammation, the predominant finding identified by histopathology, was observed as a subacute response early that progressively resolved by 28 days with only macrophage aggregates remaining late (84 days). Conclusions: Overall, there was high acute lung toxicity with a resolution of the response in mice which suggests that the Cu-Ni fume may not be ideal for reducing toxic and inflammatory lung effects. |
Tumorigenic response in lung tumor susceptible A/J mice after sub-chronic exposure to calcium chromate or iron (III) oxide
Zeidler-Erdely PC , Falcone LM , Antonini JM , Fraser K , Kashon ML , Battelli LA , Salmen R , Trainor T , Grose L , Friend S , Yang C , Erdely A . Toxicol Lett 2020 334 60-65 Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe(2)O(3)) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe(2)O(3) (1 mg) or calcium chromate (CaCrO(4); 100 µg; positive control) for 26 weeks (once per week). Shams were exposed to 50 µL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO(4) and Fe(2)O(3) significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO(4) group and neared significance in the Fe(2)O(3) group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis. |
COPEWELL: A conceptual framework and system dynamics model for predicting community functioning and resilience after disasters
Links JM , Schwartz BS , Lin S , Kanarek N , Mitrani-Reiser J , Sell TK , Watson CR , Ward D , Slemp C , Burhans R , Gill K , Igusa T , Zhao X , Aguirre B , Trainor J , Nigg J , Inglesby T , Carbone E , Kendra JM . Disaster Med Public Health Prep 2017 12 (1) 1-11 OBJECTIVE: Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster. METHODS: We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties. RESULTS: The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature. CONCLUSIONS: The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. |
Detection and molecular characterisation of noroviruses in hospitalised children in Malawi, 1997-2007
Trainor E , Lopman B , Iturriza-Gomara M , Dove W , Ngwira B , Nakagomi O , Nakagomi T , Parashar U , Cunliffe N . J Med Virol 2013 85 (7) 1299-1306 Despite the increasing recognition of noroviruses as major pathogens associated with community-acquired diarrhoea in children, there are few studies from Africa. Long-term surveillance studies of rotavirus gastroenteritis in Malawian children have provided an opportunity to undertake a study of the importance and epidemiological features of norovirus infection in this population. Faecal specimens were collected from children <5 years of age admitted to hospital with acute diarrhoea, as well as from a comparison group of diarrhoea-free children, in Blantyre, Malawi between 1997 and 2007. Norovirus was detected using real-time PCR and strains genotyped by nucleotide sequence analysis. Norovirus was detected in 220/1,941 (11.3%) faecal specimens, comprising genogroup GI (1.8%), GII (9.4%) and mixed GI/GII (0.1%). The median age of children with norovirus was 6 months (range, 0-48 months). Norovirus was detected throughout the year, with peaks at the end of the rainy season (March) and towards the end of the dry season (August-November). Norovirus GII.4 was the most commonly detected genotype accounting for 70% of strains characterised, followed by GII.2 (6%), GII.6 (4%) and GII.12 (4%). Sub typing of GII.4 noroviruses demonstrated local circulation of strains prior to their subsequent detection in association with global epidemics of gastroenteritis. The prevalence of norovirus in children without diarrhoea was similar to the level in cases. This largest study to date of norovirus infection in African children indicates the potential role of paediatric surveillance in predicting the emergence of norovirus strains with global epidemic potential. (2013 Wiley Periodicals, Inc.) |
Sculpting humoral immunity through dengue vaccination to enhance protective immunity
Crill WD , Hughes HR , Trainor NB , Davis BS , Whitney MT , Chang GJ . Front Immunol 2012 3 334 Dengue viruses (DENV) are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF). Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1) DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT) with this cross-reactivity reduced (CRR) vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from nasmall yi, Ukrainianve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine-induced immune responses. |
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