Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Barger M[original query] |
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Changes in autism and co-occurring conditions from preschool to adolescence: Considerations for precision monitoring and treatment planning
Wiggins LD , Overwyk K , Powell P , Daniels J , DiGuiseppi C , Nadler C , Reyes N , Barger B , Moody E , Pazol K . J Autism Dev Disord 2024 PURPOSE: To describe retention of an autism spectrum disorder (ASD) diagnosis from preschool to adolescence and the most common co-occurring diagnoses among children with ASD in preschool and adolescence. A second objective was to identify co-occurring diagnoses more likely to emerge between preschool and adolescence among children with ASD vs. another developmental or mental health diagnosis in preschool. METHODS: Children completed a case-control study when they were between 2 and 5 years of age. Caregivers reported their child's diagnoses of ASD and attention deficit hyperactivity disorder (ADHD), any developmental delay (DD), epilepsy/seizure disorder, obsessive-compulsive disorder, sensory integration disorder, and speech/language disorder when the child was preschool age and, separately, during adolescence. Any anxiety and depression/mood disorder, intellectual disability (ID), and learning disability (LD) were considered only in adolescence. RESULTS: 85.5% of preschool children retained their ASD diagnosis in adolescence. DD, sensory integration disorder, and speech-language disorder co-occurred in over 20% of preschool age children with ASD. These same conditions, along with anxiety disorders, ADHD, ID, and LD, co-occurred in over 20% of adolescents with ASD. Significantly more children with ASD vs. another developmental or mental health diagnosis in preschool gained diagnoses of ADHD, DD, sensory integration disorder, and speech-language disorder by adolescence. CONCLUSION: ASD is a highly stable diagnosis and co-occurring conditions are common. The prevalence of co-occurring diagnoses may depend on age, with some persisting from preschool to adolescence and others emerging over time. Health and education providers can use these findings to inform precision monitoring and treatment planning. |
Child age at time of first maternal concern and time to services among children with autism spectrum disorder
Van Dyke J , Rosenberg SA , Crume T , Reyes N , Alexander AA , Barger B , Fitzgerald R , Hightshoe K , Moody EJ , Pazol K , Rosenberg CR , Rubenstein E , Wiggins L , DiGuiseppi C . J Dev Behav Pediatr 2024 OBJECTIVE: Early treatment of autism spectrum disorder (ASD) can improve developmental outcomes. Children with ASD from minority families often receive services later. We explored factors related to child's age at time of mother's first concerns about child's development and subsequent time to service initiation among children with ASD. METHODS: Analysis included 759 preschool-age children classified with ASD based on comprehensive evaluations. Factors associated with retrospectively reported child age at time of first maternal concern and subsequent time to service initiation were investigated using multiple linear regression and Cox proportional hazards. RESULTS: Earlier maternal concern was associated with multiparity, ≥1 child chronic condition, externalizing behaviors, and younger gestational age, but not race/ethnicity. Time to service initiation was longer for children of non-Latino Black or other than Black or White race and higher developmental level and shorter for children with ≥1 chronic condition and older child age at first maternal concern. CONCLUSION: Parity, gestational age, and child health and behavior were associated with child age at first maternal concern. Knowledge of child development in multiparous mothers may allow them to recognize potential concerns earlier, suggesting that first time parents may benefit from enhanced education about normal development. Race/ethnicity was not associated with child's age when mothers recognized potential developmental problems; hence, it is unlikely that awareness of ASD symptoms causes racial/ethnic disparities in initiation of services. Delays in time to service initiation among children from racial/ethnic minority groups highlight the need to improve their access to services as soon as developmental concerns are recognized. |
Risk factors and clinical correlates of sensory dysfunction in preschool children with and without autism spectrum disorder
Wiggins LD , Overwyk K , Daniels J , Barger B , Crain H , Grzadzinski R , Moody E , Reynolds A , Reyes N , Rosenberg C , Rosenberg S , Pazol K . Autism Res 2023 Sensory dysfunction is a common feature of autism spectrum disorder (ASD). The objectives of this analysis were to examine risk factors and clinical correlates of sensory dysfunction in preschool children with and without ASD. Children aged 2-5 years were enrolled in a multi-site case-control study. Data were collected in eight areas across the United States in three phases. Caregivers completed an interview with questions on assisted delivery, maternal alcohol use, maternal anxiety during pregnancy, pregnancy weight gain, neonatal jaundice, preterm birth, and child sensory diagnosis given by a healthcare provider. Caregivers also completed an interview and questionnaires on sensory symptoms and clinical correlates of sensory dysfunction in their child. There were 2059 children classified as ASD, 3139 as other developmental delay or disability (DD), and 3249 as population comparison (POP). Caregivers reported significantly more sensory diagnoses and sensory symptoms in children classified as ASD than DD or POP (23.7%, 8.6%, and 0.8%, respectively, for a sensory diagnosis and up to 78.7% [ASD] vs. 49.6% [DD] for sensory symptoms). Maternal anxiety during pregnancy and neonatal jaundice were significantly associated with a sensory diagnosis and certain sensory symptoms in children with ASD and DD. Children's anxiety, attention deficits/hyperactivity, and sleep problems were significantly albeit subtly correlated with both a sensory diagnosis and sensory symptoms in children with ASD and DD. These findings support sensory dysfunction as a distinguishing symptom of ASD in preschool children and identify risk factors and clinical correlates to inform screening and treatment efforts in those with atypical development. |
Social and language regression: characteristics of children with autism spectrum disorder in a community-based sample
Reyes N , Soke GN , Wiggins L , Barger B , Moody E , Rosenberg C , Schieve L , Reaven J , Reynolds AM , Hepburn S . J Dev Phys Disabil 2023 This study investigated the prevalence, and the developmental, behavior and emotional outcomes of 675 preschoolers with ASD with or without a history of regression, who participated in the Study to Explore Early Development (SEED). The SEED project is a cross-sectional case-control study that collected data between 2007 and 2011. Children’s history of regression, adaptive skills, and behavior problems were assessed using the Autism Diagnostic Interview-Revised (ADI-R), the Vineland Adaptive Behavior Scales-Second Edition (Vineland-2), and the Child Behavior Checklist (CBCL), respectively; and children’s developmental levels were assessed using the Mullen Scales of Learning (MSEL). Findings from this study indicated that 26% of children experienced social and language regression, and of those with regression, 76% had regained lost skills upon completion of the study. Compared to children without a history of regression, children with social regression demonstrated increased internalizing problems and decreased fine motor skills, and children with language regression demonstrated poorer language skills. Also, children with language and social regression displayed poorer adaptive communication skills than children without regression. Children who experienced regression in one area of development demonstrated better outcomes than those who experience regression in multiple areas. To conclude, children with regression are at risk for poorer outcomes during their preschool years. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
Biological effects of inhaled crude oil vapor. III. Pulmonary inflammation, cytotoxicity, and gene expression profile
Sager TM , Joseph P , Umbright CM , Hubbs AF , Barger M , Kashon ML , Fedan JS , Roberts JR . Inhal Toxicol 2023 35 1-13 OBJECTIVE: Workers may be exposed to vapors emitted from crude oil in upstream operations in the oil and gas industry. Although the toxicity of crude oil constituents has been studied, there are very few in vivo investigations designed to mimic crude oil vapor (COV) exposures that occur in these operations. The goal of the current investigation was to examine lung injury, inflammation, oxidant generation, and effects on the lung global gene expression profile following a whole-body acute or sub-chronic inhalation exposure to COV. MATERIALS AND METHODS: To conduct this investigation, rats were subjected to either a whole-body acute (6 hr) or a sub-chronic (28 d) inhalation exposure (6 hr/d × 4 d/wk × 4 wk) to COV (300 ppm; Macondo well surrogate oil). Control rats were exposed to filtered air. One and 28 d after acute exposure, and 1, 28, and 90 d following sub-chronic exposure, bronchoalveolar lavage was performed on the left lung to collect cells and fluid for analyses, the apical right lobe was preserved for histopathology, and the right cardiac and diaphragmatic lobes were processed for gene expression analyses. RESULTS: No exposure-related changes were identified in histopathology, cytotoxicity, or lavage cell profiles. Changes in lavage fluid cytokines indicative of inflammation, immune function, and endothelial function after sub-chronic exposure were limited and varied over time. Minimal gene expression changes were detected only at the 28 d post-exposure time interval in both the exposure groups. CONCLUSION: Taken together, the results from this exposure paradigm, including concentration, duration, and exposure chamber parameters, did not indicate significant and toxicologically relevant changes in markers of injury, oxidant generation, inflammation, and gene expression profile in the lung. |
Differential performance of social communication questionnaire items in African American/Black vs. White children
Dahl E , Moody EJ , Barger B , Rosenberg S , DiGuiseppi C , Fallin MD , Lee LC , Wiggins L . J Autism Dev Disord 2023 Screening for autism spectrum disorder (ASD) is an essential early step in the identification process and inaccurate screening may lead to significant delays in the onset of treatment. Past research has highlighted discrepancies in the performance of ASD screening tools such as the Social Communication Questionnaire (SCQ) among certain racial and ethnic groups. The current study explored the functioning of the SCQ among African American/Black and White respondents based on item level performance on the measure. Differential Item Functioning (DIF) analyses showed that 16 (41%) items of the SCQ functioned differently for African American/Black respondents when compared to White respondents. Implications, such as the potential for delayed diagnosis and treatment, and the influence on downstream outcomes, are discussed. |
Research priorities to reduce risks from work hours and fatigue in the healthcare and social assistance sector
Caruso CC , Arbour MW , Berger AM , Hittle BM , Tucker S , Patrician PA , Trinkoff AM , Rogers AE , Barger LK , Edmonson JC , Landrigan CP , Redeker NS , Chasens ER . Am J Ind Med 2022 65 (11) 867-877 BACKGROUND: The services of Healthcare and Social Assistance (HCSA) workers are needed by society around the clock. As a result, these workers are exposed to shift work and long work hours. The combination of demanding work schedules and other hazards in the HCSA work environment increases the health and safety risks to these workers, as well as to their patients/clients and the public. METHODS: This paper has three aims: (1) provide an overview of the burden of shift work, long hours, and related sleep and fatigue problems in this sector; (2) suggest research priorities that would improve these; and (3) discuss potential positive impacts of addressing these research priorities for the health and safety of workers and the public. The authors used a modified Delphi approach to anonymously rank-order priorities for improving HCSA worker health and safety and public safety. Input was also obtained from attendees at the 2019 National Institute for Occupational Safety and Health (NIOSH) Work Hours, Sleep, and Fatigue Forum. RESULTS: The highest rated research priorities were developing better designs for work schedules, and improving the HCSA culture and leadership approaches to shift work and long work hours. Additional priorities are identified. CONCLUSION: Research in these priority areas has the potential to benefit HCSA workers as well as their patients/clients, employers, and society. |
Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO(2) & SiO(2)) in rats and an assessment of the impact of particle-generated oxidants on the dusts' toxicities
Lam CW , Castranova V , Zeidler-Erdely PC , Renne R , Hunter R , McCluskey R , Scully RR , Wallace WT , Zhang Y , Ryder VE , Cooper B , McKay D , McClellan RO , Driscoll KE , Gardner DE , Barger M , Meighan T , James JT . Inhal Toxicol 2022 34 51-67 Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO(2). We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (OH), showed that ground LDs>unground LDTiO(2) quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented. |
Features that best define the heterogeneity and homogeneity of autism in preschool-age children: A multisite case-control analysis replicated across two independent samples
Wiggins LD , Tian LH , Rubenstein E , Schieve L , Daniels J , Pazol K , DiGuiseppi C , Barger B , Moody E , Rosenberg S , Bradley C , Hsu M , Robinson Rosenberg C , Christensen D , Crume T , Pandey J , Levy SE . Autism Res 2021 15 (3) 539-550 The heterogeneous nature of children with symptoms of autism spectrum disorder (ASD) makes it difficult to identify risk factors and effective treatment options. We sought to identify behavioral and developmental features that best define the heterogeneity and homogeneity in 2-5-year-old children classified with ASD and subthreshold ASD characteristics. Children were enrolled in a multisite case-control study of ASD. Detailed behavioral and developmental data were gathered by maternal telephone interview, parent-administered questionnaires, child cognitive evaluation, and ASD diagnostic measures. Participants with a positive ASD screen score or prior ASD diagnosis were referred for comprehensive evaluation. Children in the ASD group met study criteria based on this evaluation; children who did not meet study criteria were categorized as having subthreshold ASD characteristics. There were 1480 children classified as ASD (81.6% boys) and 594 children classified as having subthreshold ASD characteristics (70.2% boys) in the sample. Factors associated with dysregulation (e.g., aggression, anxiety/depression, sleep problems) followed by developmental abilities (e.g., expressive and receptive language skills) most contributed to heterogeneity in both groups of children. Atypical sensory response contributed to homogeneity in children classified as ASD but not those with subthreshold characteristics. These findings suggest that dysregulation and developmental abilities are clinical features that can impact functioning in children with ASD and other DD, and that documenting these features in pediatric records may help meet the needs of the individual child. Sensory dysfunction could be considered a core feature of ASD and thus used to inform more targeted screening, evaluation, treatment, and research efforts. LAY SUMMARY: The diverse nature of autism spectrum disorder (ASD) makes it difficult to find risk factors and treatment options. We identified the most dissimilar and most similar symptom(s) in children classified as ASD and as having subthreshold ASD characteristics. Factors associated with dysregulation and developmental abilities contributed to diversity in both groups of children. Sensory dysfunction was the most common symptom in children with ASD but not those with subthreshold characteristics. Findings can inform clinical practice and research. |
Mental Health Among Parents of Children Aged <18 Years and Unpaid Caregivers of Adults During the COVID-19 Pandemic - United States, December 2020 and February-March 2021.
Czeisler MÉ , Rohan EA , Melillo S , Matjasko JL , DePadilla L , Patel CG , Weaver MD , Drane A , Winnay SS , Capodilupo ER , Robbins R , Wiley JF , Facer-Childs ER , Barger LK , Czeisler CA , Howard ME , Rajaratnam SMW . MMWR Morb Mortal Wkly Rep 2021 70 (24) 879-887 Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers(†) (1). In addition, 27% of parents of children aged <18 years reported that their mental health had worsened during the pandemic (2). To examine mental health during the COVID-19 pandemic among U.S. adults on the basis of their classification as having a parenting role (i.e., unpaid persons caring for children and adolescents aged <18 years, referred to as children in this report) or being an unpaid caregiver of adults (i.e., persons caring for adults aged ≥18 years),(§) CDC analyzed data from cross-sectional surveys that were administered during December 2020 and February-March 2021 for The COVID-19 Outbreak Public Evaluation (COPE) Initiative.(¶) Respondents were categorized as parents only, caregivers of adults only, parents-caregivers (persons in both roles), or nonparents/noncaregivers (persons in neither role). Adjusted odds ratios (aORs) for any adverse mental health symptoms, particularly suicidal ideation, were higher among all respondents who were parents, caregivers of adults, or both compared with respondents who were nonparents/noncaregivers and were highest among persons in both roles (parents-caregivers) (any adverse mental health symptoms: aOR = 5.1, 95% confidence interval [CI] = 4.1-6.2; serious suicidal ideation: aOR = 8.2, 95% CI = 6.5-10.4). These findings highlight that parents and caregivers, especially those balancing roles both as parents and caregivers, experienced higher levels of adverse mental health symptoms during the COVID-19 pandemic than adults without these responsibilities. Caregivers who had someone to rely on for support had lower odds of experiencing any adverse mental health symptoms. Additional measures are needed to improve mental health among parents, caregivers, and parents-caregivers. |
A Learning Collaborative to Improve Antibiotic Prescribing in Primary Care Pediatric Practices
Norlin C , Fleming-Dutra K , Mapp J , Monti J , Shaw A , Bartoces M , Barger K , Emmer S , Dolins JC . Clin Pediatr (Phila) 2021 60 99228211001623 An American Academy of Pediatrics State Chapter organized a 6-month, mostly online quality improvement learning collaborative to improve antibiotic prescribing and patient education for upper respiratory infection (URI) and acute otitis media (AOM). Practices submitted data on quality measures at baseline, monthly, and 4 months post-project. Fifty-three clinicians from 6 independent, private primary care pediatric practices participated. Use of first-line antibiotics for AOM increased from 63.5% at baseline to 80.4% 4 months post-project. Use of safety-net antibiotic prescriptions (SNAP) for AOM increased from 4.5% to 16.9%. Educating patients about management for URI increased from 66.1% to 88.0% and for AOM from 20.4% to 85.6%. Practices maintained high performance for not prescribing antibiotics for URI (94.4% to 96.2%). Leveraging local relationships and national resources, this replicable antibiotic stewardship project engaged independent private practices to improve patient education for URI and AOM and prescribing and use of SNAP for AOM. |
Evaluation of sex differences in preschool children with and without autism spectrum disorder enrolled in the Study to Explore Early Development
Wiggins LD , Rubenstein E , Windham G , Barger B , Croen L , Dowling N , Giarelli E , Levy S , Moody E , Soke G , Fields V , Schieve L . Res Dev Disabil 2021 112 103897 BACKGROUND AND AIMS: Research in school-aged children, adolescents, and adults with autism spectrum disorder (ASD) has found sex-based differences in behavioral, developmental, and diagnostic outcomes. These findings have not been consistently replicated in preschool-aged children. We examined sex-based differences in a large sample of 2-5-year-old children with ASD symptoms in a multi-site community-based study. METHODS AND PROCEDURES: Based on a comprehensive evaluation, children were classified as having ASD (n = 1480, 81.55 % male) or subthreshold ASD characteristics (n = 593, 70.15 % male). Outcomes were behavior problems, developmental abilities, performance on ASD screening and diagnostic tests, and parent-reported developmental conditions diagnosed before study enrollment. OUTCOMES AND RESULTS: We found no statistically significant sex differences in behavioral functioning, developmental functioning, performance on an ASD screening test, and developmental conditions diagnosed before study enrollment among children with ASD or subthreshold ASD characteristics. Males in both study groups had more parent reported restricted interests and repetitive behaviors than females, but these differences were small in magnitude and not clinically meaningful. CONCLUSIONS AND IMPLICATIONS: Preschool males and females who showed risk for ASD were more similar than different in the outcomes assessed in our study. Future research could examine sex-based differences in ASD phenotypes as children age. |
Biological effects of inhaled hydraulic fracturing sand dust. IX. Summary and significance
Anderson SE , Barger M , Batchelor TP , Bowers LN , Coyle J , Cumpston A , Cumpston JL , Cumpston JB , Dey RD , Dozier AK , Fedan JS , Friend S , Hubbs AF , Jackson M , Jefferson A , Joseph P , Kan H , Kashon ML , Knepp AK , Kodali V , Krajnak K , Leonard SS , Lin G , Long C , Lukomska E , Marrocco A , Marshall N , Mc Kinney W , Morris AM , Olgun NS , Park JH , Reynolds JS , Roberts JR , Russ KA , Sager TM , Shane H , Snawder JE , Sriram K , Thompson JA , Umbright CM , Waugh S , Zheng W . Toxicol Appl Pharmacol 2020 409 115330 An investigation into the potential toxicological effects of fracking sand dust (FSD), collected from unconventional gas drilling sites, has been undertaken, along with characterization of their chemical and biophysical properties. Using intratracheal instillation of nine FSDs in rats and a whole body 4-d inhalation model for one of the FSDs, i.e., FSD 8, and related in vivo and in vitro experiments, the effects of nine FSDs on the respiratory, cardiovascular and immune systems, brain and blood were reported in the preceding eight tandem papers. Here, a summary is given of the key observations made in the organ systems reported in the individual studies. The major finding that inhaled FSD 8 elicits responses in extra-pulmonary organ systems is unexpected, as is the observation that the pulmonary effects of inhaled FSD 8 are attenuated relative to forms of crystalline silica more frequently used in animal studies, i.e., MIN-U-SIL®. An attempt is made to understand the basis for the extra-pulmonary toxicity and comparatively attenuated pulmonary toxicity of FSD 8. |
Biological effects of inhaled hydraulic fracturing sand dust. II. Particle characterization and pulmonary effects 30 d following intratracheal instillation
Fedan JS , Hubbs AF , Barger M , Schwegler-Berry D , Friend SA , Leonard SS , Thompson JA , Jackson MC , Snawder JE , Dozier AK , Coyle J , Kashon ML , Park JH , McKinney W , Roberts JR . Toxicol Appl Pharmacol 2020 409 115282 Hydraulic fracturing ("fracking") is used in unconventional gas drilling to allow for the free flow of natural gas from rock. Sand in fracking fluid is pumped into the well bore under high pressure to enter and stabilize fissures in the rock. In the process of manipulating the sand on site, respirable dust (fracking sand dust, FSD) is generated. Inhalation of FSD is a potential hazard to workers inasmuch as respirable crystalline silica causes silicosis, and levels of FSD at drilling work sites have exceeded occupational exposure limits set by OSHA. In the absence of any information about its potential toxicity, a comprehensive rat animal model was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems (Fedan, J.S., Toxicol Appl Pharmacol. 00, 000-000, 2020). The present report, part of the larger investigation, describes: 1) a comparison of the physico-chemical properties of nine FSDs, collected at drilling sites, and MIN-U-SIL® 5, a reference silica dust, and 2) a comparison of the pulmonary inflammatory responses to intratracheal instillation of the nine FSDs and MIN-U-SIL® 5. Our findings indicate that, in many respects, the physico-chemical characteristics, and the biological effects of the FSDs and MIN-U-SIL® 5 after intratracheal instillation, have distinct differences. |
Biological effects of inhaled hydraulic fracturing sand dust. IV. Pulmonary effects
Russ KA , Thompson JA , Reynolds JS , Mercer RR , Porter DW , McKinney W , Dey RD , Barger M , Cumpston J , Batchelor TP , Kashon ML , Kodali V , Jackson MC , Sriram K , Fedan JS . Toxicol Appl Pharmacol 2020 409 115284 Hydraulic fracturing creates fissures in subterranean rock to increase the flow and retrieval of natural gas. Sand ("proppant") in fracking fluid injected into the well bore maintains fissure patency. Fracking sand dust (FSD) is generated during manipulation of sand to prepare the fracking fluid. Containing respirable crystalline silica, FSD could pose hazards similar to those found in work sites where silica inhalation induces lung disease such as silicosis. This study was performed to evaluate the possible toxic effects following inhalation of a FSD (FSD 8) in the lung and airways. Rats were exposed (6 h/d × 4 d) to 10 or 30 mg/m(3) of a FSD, i.e., FSD 8, collected at a gas well, and measurements were performed 1, 7, 27 and, in one series of experiments, 90 d post-exposure. The following ventilatory and non-ventilatory parameters were measured in vivo and/or in vitro: 1) lung mechanics (respiratory system resistance and elastance, tissue damping, tissue elastance, Newtonian resistance and hysteresivity); 2) airway reactivity to inhaled methacholine (MCh); airway epithelium integrity (isolated, pefused trachea); airway efferent motor nerve activity (electric field stimulation in vitro); airway smooth muscle contractility; ion transport in intact and cultured epithelium; airway effector and sensory nerves; tracheal particle deposition; and neurogenic inflammation/vascular permeability. FSD 8 was without large effect on most parameters, and was not pro-inflammatory, as judged histologically and in cultured epithelial cells, but increased reactivity to inhaled MCh at some post-exposure time points and affected Na(+) transport in airway epithelial cells. |
Biological effects of inhaled hydraulic fracturing sand dust. V. Pulmonary inflammatory, cytotoxic and oxidant effects.
Sager TM , Roberts JR , Umbright CM , Barger M , Kashon ML , Fedan JS , Joseph P . Toxicol Appl Pharmacol 2020 408 115280 The pulmonary inflammatory response to inhalation exposure to a fracking sand dust (FSD 8) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol of a FSD, i.e., FSD 8, at concentrations of 10 or 30 mg/m(3), 6 h/d for 4 d. The control and FSD 8-exposed rats were euthanized at post-exposure time intervals of 1, 7 or 27 d and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Deposition of FSD 8 particles was detected in the lungs of all the FSD 8-exposed rats. Analysis of bronchoalveolar lavage parameters of toxicity, oxidant generation, and inflammation did not reveal any significant persistent pulmonary toxicity in the FSD 8-exposed rats. Similarly, the lung histology of the FSD 8-exposed rats showed only minimal changes in influx of macrophages following the exposure. Determination of global gene expression profiles detected statistically significant differential expressions of only six and five genes in the 10 mg/m(3), 1-d post-exposure, and the 30 mg/m(3), 7-d post-exposure FSD 8 groups, respectively. Taken together, data obtained from the present study demonstrated that FSD 8 inhalation exposure resulted in no statistically significant toxicity or gene expression changes in the lungs of the rats. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) has been designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems. |
Demographic Characteristics, Experiences, and Beliefs Associated with Hand Hygiene Among Adults During the COVID-19 Pandemic - United States, June 24-30, 2020.
Czeisler MÉ , Garcia-Williams AG , Molinari NA , Gharpure R , Li Y , Barrett CE , Robbins R , Facer-Childs ER , Barger LK , Czeisler CA , Rajaratnam SMW , Howard ME . MMWR Morb Mortal Wkly Rep 2020 69 (41) 1485-1491 Frequent hand hygiene, including handwashing with soap and water or using a hand sanitizer containing ≥60% alcohol when soap and water are not readily available, is one of several critical prevention measures recommended to reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* Previous studies identified demographic factors associated with handwashing among U.S. adults during the COVID-19 pandemic (1,2); however, demographic factors associated with hand sanitizing and experiences and beliefs associated with hand hygiene have not been well characterized. To evaluate these factors, an Internet-based survey was conducted among U.S. adults aged ≥18 years during June 24-30, 2020. Overall, 85.2% of respondents reported always or often engaging in hand hygiene following contact with high-touch public surfaces such as shopping carts, gas pumps, and automatic teller machines (ATMs).(†) Respondents who were male (versus female) and of younger age reported lower handwashing and hand sanitizing rates, as did respondents who reported lower concern about their own infection with SARS-CoV-2(§) and respondents without personal experience with COVID-19. Focused health promotion efforts to increase hand hygiene adherence should include increasing visibility and accessibility of handwashing and hand sanitizing materials in public settings, along with targeted communication to males and younger adults with focused messages that address COVID-19 risk perception. |
Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic - United States, June 24-30, 2020.
Czeisler ME , Lane RI , Petrosky E , Wiley JF , Christensen A , Njai R , Weaver MD , Robbins R , Facer-Childs ER , Barger LK , Czeisler CA , Howard ME , Rajaratnam SMW . MMWR Morb Mortal Wkly Rep 2020 69 (32) 1049-1057 The coronavirus disease 2019 (COVID-19) pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders.* Symptoms of anxiety disorder and depressive disorder increased considerably in the United States during April-June of 2020, compared with the same period in 2019 (1,2). To assess mental health, substance use, and suicidal ideation during the pandemic, representative panel surveys were conducted among adults aged ≥18 years across the United States during June 24-30, 2020. Overall, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of a trauma- and stressor-related disorder (TSRD) related to the pandemic(†) (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%). The percentage of respondents who reported having seriously considered suicide in the 30 days before completing the survey (10.7%) was significantly higher among respondents aged 18-24 years (25.5%), minority racial/ethnic groups (Hispanic respondents [18.6%], non-Hispanic black [black] respondents [15.1%]), self-reported unpaid caregivers for adults(§) (30.7%), and essential workers(¶) (21.7%). Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic. |
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. |
Public Attitudes, Behaviors, and Beliefs Related to COVID-19, Stay-at-Home Orders, Nonessential Business Closures, and Public Health Guidance - United States, New York City, and Los Angeles, May 5-12, 2020.
Czeisler ME , Tynan MA , Howard ME , Honeycutt S , Fulmer EB , Kidder DP , Robbins R , Barger LK , Facer-Childs ER , Baldwin G , Rajaratnam SMW , Czeisler CA . MMWR Morb Mortal Wkly Rep 2020 69 (24) 751-758 SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to be transmitted mainly by person-to-person contact (1). Implementation of nationwide public health orders to limit person-to-person interaction and of guidance on personal protective practices can slow transmission (2,3). Such strategies can include stay-at-home orders, business closures, prohibitions against mass gatherings, use of cloth face coverings, and maintenance of a physical distance between persons (2,3). To assess and understand public attitudes, behaviors, and beliefs related to this guidance and COVID-19, representative panel surveys were conducted among adults aged >/=18 years in New York City (NYC) and Los Angeles, and broadly across the United States during May 5-12, 2020. Most respondents in the three cohorts supported stay-at-home orders and nonessential business closures* (United States, 79.5%; New York City, 86.7%; and Los Angeles, 81.5%), reported always or often wearing cloth face coverings in public areas (United States, 74.1%, New York City, 89.6%; and Los Angeles 89.8%), and believed that their state's restrictions were the right balance or not restrictive enough (United States, 84.3%; New York City, 89.7%; and Los Angeles, 79.7%). Periodic assessments of public attitudes, behaviors, and beliefs can guide evidence-based public health decision-making and related prevention messaging about mitigation strategies needed as the COVID-19 pandemic evolves. |
Cervical cancer risk in women living with HIV across four continents: A multicohort study
Rohner E , Butikofer L , Schmidlin K , Sengayi M , Maskew M , Giddy J , Taghavi K , Moore RD , Goedert JJ , Gill MJ , Silverberg MJ , D'Souza G , Patel P , Castilho JL , Ross J , Sohn A , Bani-Sadr F , Taylor N , Paparizos V , Bonnet F , Verbon A , Vehreschild JJ , Post FA , Sabin C , Mocroft A , Dronda F , Obel N , Grabar S , Spagnuolo V , Quiros-Roldan E , Mussini C , Miro JM , Meyer L , Hasse B , Konopnicki D , Roca B , Barger D , Clifford GM , Franceschi S , Egger M , Bohlius J . Int J Cancer 2020 146 (3) 601-609 We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/mul decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities. |
State variability in diagnosed conditions for IDEA Part C Eligibility
Barger B , Squires J , Greer M , Noyes-Grosser D , Eile JM , Rice C , Shaw E , Surprenant KS , Twombly E , London S , Zubler J , Wolf RB . Infants Young Child 2019 32 (4) 231-244 An infant or toddler can begin the process of receiving Part C early intervention services by having a diagnosed condition with a high probability of developmental delay (Individuals with Disabilities Education Improvement Act, 2004). How states define those diagnosed conditions that begin the initiation process varies widely. Lists of diagnosed conditions were collected from state Part C websites and Part C coordinators for a descriptive analysis. Across 49 states, the District of Columbia, and 4 territories, a final list of 620 unique conditions was compiled. No single condition was listed by all jurisdictions. Hearing impairment was the condition listed by the most states (n = 38), followed by fetal alcohol syndrome (n = 34). Of the 620 conditions, 168 (27%) were listed by only 1 state, 554 (89%) were listed by fewer than 10 states, and 66 (11%) were listed by 10 or more states. Of these 66 conditions, 47 (71%) were listed by fewer than 20 states. Most of these 66 conditions (n = 48; 72.7%) had a prevalence of "very rare or rare," 8 (12%) were "common," 6 (9%) were "very common," and 4 (6.1%) were "unknown." The wide heterogeneity in the number and type of diagnostic conditions listed across states should be further investigated as it may represent imbalances in children with diagnosed conditions gaining access to Part C evaluations and individualized family service plans and potentially the services themselves across states. In addition, providing ready access to lists of diagnosed conditions is a simple step that could help states and Part C programs facilitate access to services. |
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. |
DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children
Wiggins LD , Rice CE , Barger B , Soke GN , Lee LC , Moody E , Edmondson-Pretzel R , Levy SE . Soc Psychiatry Psychiatr Epidemiol 2019 54 (6) 693-701 PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children. |
Temperament similarities and differences: A comparison of factor structures from the Behavioral Style Questionnaire in children with and without autism spectrum disorder
Barger B , Moody EJ , Ledbetter C , D'Abreu L , Hepburn S , Rosenberg SA . J Autism Dev Disord 2019 49 (5) 1749-1762 The majority of studies of temperament in children with autism spectrum disorder (ASD) use scales normed on typical populations. The present study examined a widely used measure of temperament, the Behavioral Style Questionnaire (McDevitt and Carey in Behavioral Styles Questionnaire, Behavioral-Developmental Initiatives Scottsdale, AZ, 1975) to determine whether it contains the temperament traits theorized by its creators. Neither confirmatory nor exploratory factor analysis, using a sample of children with ASD and a population comparison group, identified the theorized nine temperament factors; many items did not strongly load on any of the original factors. A 10 factor solution best described the ASD data and a 9 factor solution best described the typical group's data. There were substantial similarities in the 9 factor solutions, but groups differed from one another enough to question construct similarity for several factors. These results highlight that more basic psychometric research is needed to better understand the BSQ in children with ASD. |
Sexually transmitted infections in the Delta Regional Authority: significant disparities in the 252 counties of the eight-state Delta Region Authority
Barger AC , Pearson WS , Rodriguez C , Crumly D , Mueller-Luckey G , Jenkins WD . Sex Transm Infect 2018 94 (8) 611-615 OBJECTIVE: Chlamydia, gonorrhoea and syphilis (primary and secondary) are at high levels in the USA. Disparities by race, gender and sexual orientation have been characterised, but while there are indications that rural poor populations may also be at distinct risk this has been subjected to little study by comparison. The federally designated Delta Regional Authority, similar in structure to the Appalachian Regional Commission, oversees 252 counties within eight Mississippi Delta states experiencing chronic economic and health disparities. Our objective was to identify differences in infection risk between Delta Region (DR)/non-DR counties and examine how they might vary by rurality, population density, primary care access and education attainment. METHODS: Reported chlamydia/gonorrhoea/syphilis data were obtained from the Centers for Disease Control and Prevention AtlasPlus, county demographic data from the Area Health Resource File and rurality classifications from the Department of Agriculture. Data were subjected to analysis by t-test, chi(2) and linear regression to assess geographical disparities in incidence and their association with measures of rurality, population and primary care density, and education. RESULTS: Overall rates for each infection were significantly higher in DR versus non-DR counties (577.8 vs 330.1/100 000 for chlamydia; 142.8 vs 61.8 for gonorrhoea; 3.6 vs 1.7 for syphilis; all P<0.001) and for nearly every infection for every individual state. DR rates for each infection were near-universally significantly increased for every level of rurality (nine levels) and population density (quintiles). Regression found that primary care and population density and HS graduation rates were significantly associated with each, though model predictive abilities were poor. CONCLUSIONS: The nearly 10 million people living in the DR face significant disparities in the incidence of chlamydia, gonorrhoea and syphilis-in many instances a near-doubling of risk. Our findings suggest that resource-constrained areas, as measured by rurality, should be considered a priority for future intervention efforts. |
A systematic review of part C early identification studies
Barger B , Rice C , Simmons CA , Wolf R . Topics Early Child Spec Educ 2018 38 (1) 4-16 Authors conducted a systematic literature review on early identification steps leading at-risk young children to connect with Part C services. Authors classified data collection settings as primary (settings for general population) or specialized (settings for children at risk of developmental delay) and according to the phases of early identification in the study: (a) original population of children aged 0 to 6 years who had received Part C services, (b) screening and/or referral and/or developmental assessment from 0 through age 2 years, and (c) were deemed eligible and/or received Part C services. Authors identified 43 articles including at least two phases of the early identification process. The literature about connecting children to Part C early intervention (EI) is sparse and fragmented; few studies document the full process from community monitoring to service receipt. Results indicate opportunities for development of systems to better track and improve the identification of young children in need of EI. |
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. |
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. |
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