Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 328 Records) |
Query Trace: Ford N [original query] |
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Mixtures of urinary phenol and phthalate metabolite concentrations in relation to serum lipid levels among pregnant women: Results from the EARTH Study
Shen X , Génard-Walton M , Williams PL , James-Todd T , Ford JB , Rexrode KM , Calafat AM , Zhang D , Chavarro JE , Hauser R , Mínguez-Alarcón L , The Earth Study Team . Toxics 2024 12 (8) We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. |
A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex
Michon M , Müller-Schiffmann A , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Müller L , Ostermann PN , Andrée M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad DM , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . Open Biol 2024 14 (6) 230363 We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease. |
Gestational diabetes prevalence estimates from three data sources, 2018
Bolduc MLF , Mercado CI , Zhang Y , Lundeen EA , Ford ND , Bullard KM , Carty DC . Matern Child Health J 2024 INTRODUCTION: We investigated 2018 gestational diabetes mellitus (GDM) prevalence estimates in three surveillance systems (National Vital Statistics System, State Inpatient Database, and Pregnancy Risk Assessment Monitoring Survey). METHODS: We calculated GDM prevalence for jurisdictions represented in each system; a subset of data was analyzed for people 18-39 years old in 22 jurisdictions present in all three systems to observe dataset-specific demographics and GDM prevalence using comparable categories. RESULTS: GDM prevalence estimates varied widely by data system and within the data subset despite comparable demographics. DISCUSSION: Understanding the differences between GDM surveillance data systems can help researchers better identify people and places at higher risk of GDM. |
Environmental phenols and growth in infancy: The Infant Feeding and Early Development Study
Stevens DR , Goldberg M , Adgent M , Chin HB , Baird DD , Stallings VA , Sandler DP , Calafat AM , Ford EG , Zemel BS , Kelly A , Umbach DM , Rogan W , Ferguson KK . J Clin Endocrinol Metab 2024 CONTEXT: Higher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols. OBJECTIVE: In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants. METHODS: We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (β [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]). RESULTS: Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively). CONCLUSION: Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure. |
Health insurance and access to care in U.S. working age adults experiencing long COVID
Ford ND , Slaughter D , Dalton AF , Edwards D , Ma K , King H , Saydah S . Am J Prev Med 2024 INTRODUCTION: Long COVID encompasses a wide range of health problems that emerge, persist, or recur following acute COVID-19 illness. Given that the prevalence of self-reported Long COVID is highest among U.S. adults in their prime working years, it is important to identify unmet needs and gaps in healthcare access and coverage among working age adults. METHODS: Prevalences (95% CI) of health insurance coverage and access to care by Long COVID status were estimated among adults 18-64 years (n = 18,117), accounting for survey design and weighted to the U.S. non-institutionalized population in the 2022 National Health Interview Survey. Analyses were conducted in 2023. RESULTS: Overall, 3.7% (95% CI 3.4, 4.0) of respondents were experiencing Long COVID. Adults experiencing Long COVID were less likely to report being uninsured relative to adults not experiencing Long COVID (P=0.004); however, 49.0% (95% CI 43.2, 54.7) had high deductible health plans. Adjusting for sociodemographic characteristics, adults experiencing Long COVID were more likely to access healthcare compared to adults not experiencing Long COVID (P<0.01 for seeing a doctor, telemedicine appointments, ≥2 urgent care visits, ≥2 emergency department visits, and hospitalized overnight). Despite more frequent healthcare use, adults experiencing Long COVID were also more likely to abstain from and delay medical care, therapy, and prescriptions due to cost compared to adults not experiencing Long COVID (P<0.0001 for all comparisons). CONCLUSIONS: These findings may be used to inform healthcare planning for adults experiencing Long COVID and highlight the ongoing need to improve access and affordability of quality and comprehensive care. |
Environmental phenol exposures in 6- to 12-week-old infants: the Infant Feeding and Early Development (IFED) Study
Goldberg M , Adgent MA , Stevens DR , Chin HB , Ferguson KK , Calafat AM , Travlos G , Ford EG , Stallings VA , Rogan WJ , Umbach DM , Baird DD , Sandler DP . Environ Res 2024 119075 BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (μg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development. |
Benzophenone-3 and ovarian reserve
Silva EL , Mínguez-Alarcón L , Coull B , Hart JE , James-Todd T , Calafat AM , Ford JB , Hauser R , Mahalingaiah S . Fertil Steril 2024 OBJECTIVE: To evaluate the association between urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health (EARTH) Study seeking fertility treatment at Massachusetts General Hospital in Boston, Massachusetts. DESIGN: Prospective cohort study. METHODS: Women from the EARTH cohort contributed spot urine samples before assessment of OR outcomes. Antral follicle count (AFC) and day-3 follicle stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of specific gravity (SG)-adjusted urinary benzophenone-3 concentrations with AFC and FSH, respectively, with adjustment for age and physical activity. In secondary analyses, models were stratified by age. Sensitivity analyses assessed for confounding by season by restricting to women with exposure and outcome measured in the same season and stratifying by summer vs. non-summer months and for confounding by sunscreen use by restricting to women who filled out product questionnaires and adjusting for and stratifying by average sunscreen use score. RESULTS: The study included 142 women (mean age ± SD, 36.1 ± 4.6; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC and 57 women with benzophenone-3 and FSH measurements. Most women were white (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10) with 37% contributing 2 or more samples. Benzophenone-3 was detected in 98% of samples. Geometric mean (GM) SG-corrected urinary benzophenone-3 concentration was 85.9 μ g/L (geometric standard deviation 6.2). There were no associations of benzophenone-3 with AFC and day-3 FSH in the full cohort. In stratified models, a 1-unit increase in log GM benzophenone-3 was associated with AFC 0.91 (95% CI, 0.86, 0.97) times lower among women ≤35 years old and was associated with FSH 0.73 (95% CI, 0.12, 1.34) IU/L higher among women >35 years old. Effect estimates from models stratified by season and sunscreen use were null. CONCLUSION: In main models, urinary benzophenone-3 was not associated with OR. However, younger may be vulnerable to potential effects of benzophenone-3 on AFC. Further research is warranted. |
Notes from the field: Long COVID prevalence among adults - United States, 2022
Ford ND , Agedew A , Dalton AF , Singleton J , Perrine CG , Saydah S . MMWR Morb Mortal Wkly Rep 2024 73 (6) 135-136 |
Associations of parental preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-a concentrations with child eating behaviors
Leader J , Mínguez-Alarcón L , Williams PL , Ford JB , Dadd R , Chagnon O , Oken E , Calafat AM , Hauser R , Braun JM . Int J Hyg Environ Health 2024 257 114334 BACKGROUND: Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors. METHODS: We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores. RESULTS: This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (β(')s= 0.11 [95% CI: 0.01, 0.20]-0.21 [95% CI: 0.10, 0.31] per log(e) unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores. CONCLUSIONS: In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children. |
Power law for estimating underdetection of foodborne disease outbreaks, United States
Ford L , Self JL , Wong KK , Hoekstra RM , Tauxe RV , Rose EB , Bruce BB . Emerg Infect Dis 2023 30 (2) 337-340 We fit a power law distribution to US foodborne disease outbreaks to assess underdetection and underreporting. We predicted that 788 fewer than expected small outbreaks were identified annually during 1998-2017 and 365 fewer during 2018-2019, after whole-genome sequencing was implemented. Power law can help assess effectiveness of public health interventions. |
Recapitulation of human pathophysiology and identification of forensic biomarkers in a translational model of chlorine inhalation injury
Achanta S , Gentile MA , Albert CJ , Schulte KA , Pantazides BG , Crow BS , Quinones-Gonzalez J , Perez JW , Ford DA , Patel RP , Blake TA , Gunn MD , Jordt SE . Am J Physiol Lung Cell Mol Physiol 2024 Chlorine gas (Cl(2)) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl(2) exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl(2)-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl(2)-induced ALI in swine to understand toxico-pathophysiology and is suitable for screening potential medical countermeasures, and identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl(2) (≤ 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl(2) resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl(2) exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid (BALF), vascular leakage, and pulmonary edema compared to the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2‑chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung tissue after Cl(2)‑exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl(2) inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl(2) inhalation. |
Efficacy of unregulated minimum risk tick repellent products evaluated with Ixodes scapularis nymphs in a human skin bioassay
Burtis JC , Ford SL , Parise CM , Eisen RJ , Eisen L . Parasit Vectors 2024 17 (1) 50 BACKGROUND: The majority of vector-borne disease cases in the USA are caused by pathogens spread by ticks, most commonly the blacklegged tick, Ixodes scapularis. Personal protection against tick bites, including use of repellents, is the primary defense against tick-borne diseases. Tick repellents registered by the Environmental Protection Agency (EPA) are well documented to be safe as well as effective against ticks. Another group of tick repellent products, 25(b) exempt or minimum risk products, use alternative, mostly botanically derived, active ingredients. These are considered to pose minimal risk to human health and therefore are exempt from EPA registration; efficacy testing is not mandated for these products. METHODS: We used a finger bioassay to evaluate the repellency against I. scapularis nymphs for 11 formulated 25(b) exempt products together with two positive control DEET-based EPA registered products. Repellency was assessed hourly from 0.5 to 6.5 h after product application. RESULTS: The DEET-based products showed ≥ 97% repellency for all examined timepoints. By contrast, an average of 63% of ticks were repelled in the first 1.5 h after application across the 11 25(b) exempt products, and the average fell to 3% repelled between 2.5 and 6.5 h. Ten of the 11 25(b) exempt products showed statistically similar efficacy to DEET-based products at 30 min after application (repellency of 79-97%). However, only four 25(b) exempt products maintained a level of repellency similar to DEET-based products (> 72%) at the 1.5-h mark, and none of these products were effective in repelling ticks at the timepoints from 2.5 to 6.5 h after application. CONCLUSIONS: Neither the claims on the labels nor specific active ingredients and their concentrations appeared to predict the duration of efficacy we observed for the 25(b) exempt products. These products are not registered with the EPA, so the methods used to determine the application guidelines on their labels are unclear. Consumers should be aware that both the level of efficacy and the duration of repellency may differ among unregulated 25(b) exempt repellent products labeled for use against ticks. We encourage more research on these products and the 25(b) exempt active ingredients they contain to help determine and improve their efficacy as repellents under different conditions. |
Hospitalization with cardiovascular conditions in the postpartum year among commercially insured women in the U.S
Ford ND , DeSisto CL , Womack LS , Galang RR , Hollier LM , Sperling LS , Wright JS , Ko JY . J Am Coll Cardiol 2024 83 (2) 382-384 Cardiovascular conditions are significant contributors to morbidity and mortality among pregnant and postpartum women.1 | | We used data from the MarketScan Commercial Claims and Encounters database to identify women 12 to 55 years of age who delivered from 2017 to 2019. Delivery hospitalizations and cardiovascular diagnoses and procedures (ie, conditions) were identified using International Classification of Diseases-10th Revision-Clinical Modification codes. Cardiovascular conditions included acute heart failure or pulmonary edema; acute myocardial infarction; arrhythmia; conduction disorders; cardiac arrest, ventricular fibrillation, or ventricular flutter; cardiomyopathy; congenital heart and great artery defects; conversion of cardiac rhythm; endocarditis, myocarditis, or pericarditis; hypertensive heart disease; ischemic heart disease; nonrheumatic valve disorders; pulmonary heart disease; rheumatic heart disease; and other heart diseases and complications. We calculated the prevalence of hospitalizations with any cardiovascular condition in the year postpartum. Among these patients, we calculated the prevalence of cardiovascular conditions at delivery hospitalization and the frequency of postpartum hospitalizations. For postpartum hospitalizations with cardiovascular conditions, we calculated timing relative to delivery hospitalization and the prevalence (95% CI) of specific cardiovascular conditions by timing since delivery hospitalization (early postpartum [1–42 days] vs late postpartum [43–365 days]), accounting for clustering at the patient level. The data were collected and statistically deidentified. The data are also compliant with the conditions set forth in sections 164.514(a) and 164.51(b)(1)(ii) of the Health Insurance Portability and Accountability Act of 1996 Privacy Rule; therefore, approval from an Institutional Review Board was not sought. |
Paternal and maternal preconception and maternal pregnancy urinary concentrations of parabens in relation to child behavior
Leader J , Mínguez-Alarcón L , Williams PL , Ford JB , Dadd R , Chagnon O , Bellinger DC , Oken E , Calafat AM , Hauser R , Braun JM . Andrology 2023 BACKGROUND: Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6-13 years and their parents. We estimated covariate-adjusted associations of log(e) -transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g-computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 and Behavior Rating Inventory of Executive Function T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non-Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T-scores (propyl paraben β = 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β = 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben β = 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β = 1.6; 95% confidence interval: -0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T-scores respectively. Higher paternal preconception ( β = 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( β = 1.1 95% confidence interval: -0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T-scores in children, but the paraben mixtures was not. CONCLUSION: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors. |
Poliovirus serological assay after the cVDPV1 outbreak in Papua New Guinea: a cross-sectional study from 2020 to 2021
Pomat W , Lopez Cavestany R , Jeyaseelan V , Ford R , Gare J , Avagyan T , Grabovac V , Bettels D , Mekonnen D , Jones KAV , Mainou BA , Mach O . Lancet Reg Health West Pac 2024 44 Background: In June 2018, a type 1 circulating vaccine-derived poliovirus (cVDPV1) outbreak was declared in Papua New Guinea (PNG), resulting in a total of 26 paralytic confirmed cases. Eight vaccination campaign rounds with bivalent oral poliovirus vaccine (bOPV) were carried out in response. Prevalence of neutralizing polio antibodies in children was assessed two years after the outbreak response was completed. Methods: We conducted a cross-sectional serological survey among children aged 6 months–10 years selected from six provinces in PNG to evaluate seroprevalence of neutralizing polio antibodies to the three poliovirus serotypes and analyse sociodemographic risk factors. Findings: We included 984 of 1006 enrolled children in the final analysis. The seroprevalence of neutralizing polio antibodies for serotype 1, 2 and 3 was 98.3% (95% CI: 97.4–98.9), 63.1% (95% CI: 60.1–66.1) and 95.0% (95% CI: 93.6–96.3), respectively. Children <1 year had significantly lower type 1 seroprevalence compared to older children (p < 0.001); there were no significant differences in seroprevalence among provinces. Interpretation: PNG successfully interrupted transmission of cVDPV1 with several high coverage bOPV campaigns and seroprevalence remained high after two years. The emergence of cVDPV strains underscores the importance of maintaining high levels of routine immunization coverage and effective surveillance systems for early detection. Funding: World Health Organization through a Rotary International IPPC grant. © 2023 |
Marijuana use among pregnant and nonpregnant women of reproductive age, 2013-2019
Kobernik EK , Ford ND , Levecke M , Galang RR , Hoots B , Roehler DR , Ko JY . Subst Use Misuse 2023 1-9 BACKGROUND: Marijuana is the most commonly used federally illicit substance among reproductive-age women in the United States. Updated information on marijuana use in this population can inform clinical and public health interventions. METHODS: Data from the 2013-2019 National Survey on Drug Use and Health was used to report weighted prevalence estimates of marijuana use in the past month, past 2-12 months, and past year among women aged 18-44 years with self-reported pregnancy status. Bivariate analyses and general linear regression models with Poisson distribution using appropriate survey procedures identified factors associated with past-year marijuana use by pregnancy status. RESULTS: Among pregnant women, 4.9% (95% confidence interval [CI]: 4.1-5.6) reported marijuana use in the past month, 10.4% (95% CI: 9.3-11.5) in the past 2-12 months, and 15.2% (95% CI: 13.9-16.6) in the past year. Among nonpregnant women, 11.8% (95% CI: 11.5-12.0) reported marijuana use in the past month, 7.8% (95% CI: 7.6-8.0) in the past 2-12 months, and 19.5% (95% CI: 19.2-19.9) in the past year. After adjusting for sociodemographic characteristics, past-year marijuana use was 2.3-5.1 times more likely among pregnant, and 2.1 to 4.6 times more likely among nonpregnant women who reported past-year tobacco smoking, alcohol use, or other illicit drug use compared to those reporting no substance use. CONCLUSIONS: Pregnant and nonpregnant women reporting marijuana use, alone or with other substances, can benefit from substance use screening and treatment facilitation. |
Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior
Leader J , Mínguez-Alarcón L , Williams PL , Ford JB , Dadd R , Chagnon O , Bellinger DC , Oken E , Calafat AM , Hauser R , Braun JM . Environ Int 2023 183 108337 BACKGROUND: Epidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-log(e) unit increase; 95 % CI: -0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: -1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: -2.1, -0.4). CONCLUSION: In this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores. |
Healthcare providers' knowledge and clinical practice surrounding shigellosis - DocStyles Survey, 2020
Haston JC , Ford L , Vanden Esschert KL , Plumb ID , Logan N , Francois Watkins LK , Garcia-Williams AG . BMC Prim Care 2023 24 (1) 267 BACKGROUND: Shigellosis is an acute diarrheal disease transmitted through contaminated food, water, objects, poor hand hygiene, or sexual activity. Healthcare providers (HCP) may not be aware of the multiple routes of Shigella transmission, populations at increased risk, or importance of antibiotic susceptibility testing (AST). This study assessed HCP knowledge and clinical practices regarding shigellosis and antibiotic resistance. METHODS: Porter Novelli Public Services administered a web-based survey (Fall DocStyles 2020) to HCP in the United States. Pediatricians, primary care physicians, nurse practitioners, and physician assistants completed questions about knowledge and clinical practice of acute diarrhea and shigellosis. RESULTS: Of 2196 HCP contacted, 1503 responded (68% response rate). Most identified contaminated food (85%) and water (79%) as routes of Shigella transmission; fewer recognized person-to-person contact (40%) and sexual activity (18%). Men who have sex with men (MSM) were identified as being at risk for shigellosis by 35% of respondents. Most reported counseling patients to wash hands (86%) and avoid food preparation (77%) when ill with shigellosis; 29% reported recommending avoiding sex. Many HCP reported treating shigellosis empirically with ciprofloxacin (62%) and azithromycin (32%), and 29% reported using AST to guide treatment. CONCLUSIONS: We identified several gaps in shigellosis knowledge among HCP including MSM as a risk group, person-to-person transmission, and appropriate antibiotic use. Improving HCP education could prevent the spread of shigellosis, including drug-resistant infections, among vulnerable populations. |
Implementation Strategies to Improve Blood Pressure Control in the United States: A Scientific Statement From the American Heart Association and American Medical Association
Abdalla M , Bolen SD , Brettler J , Egan BM , Ferdinand KC , Ford CD , Lackland DT , Wall HK , Shimbo D . Hypertension 2023 80 (10) e143-e157 Hypertension is one of the most important risk factors that contribute to incident cardiovascular events. A multitude of US and international hypertension guidelines, scientific statements, and policy statements have recommended evidence-based approaches for hypertension management and improved blood pressure (BP) control. These recommendations are based largely on high-quality observational and randomized controlled trial data. However, recent published data demonstrate troubling temporal trends with declining BP control in the United States after decades of steady improvements. Therefore, there is a widening disconnect between what hypertension experts recommend and actual BP control in practice. This scientific statement provides information on the implementation strategies to optimize hypertension management and to improve BP control among adults in the United States. Key approaches include antiracism efforts, accurate BP measurement and increased use of self-measured BP monitoring, team-based care, implementation of policies and programs to facilitate lifestyle change, standardized treatment protocols using team-based care, improvement of medication acceptance and adherence, continuous quality improvement, financial strategies, and large-scale dissemination and implementation. Closing the gap between scientific evidence, expert recommendations, and achieving BP control, particularly among disproportionately affected populations, is urgently needed to improve cardiovascular health. |
Strain of multidrug-resistant salmonella newport remains linked to travel to Mexico and U.S. beef products - United States, 2021-2022
Ford L , Ellison Z , Schwensohn C , Griffin I , Birhane MG , Cote A , Fortenberry GZ , Tecle S , Higa J , Spencer S , Patton B , Patel J , Dow J , Maroufi A , Robbins A , Donovan D , Fitzgerald C , Burrell S , Tolar B , Folster JP , Cooley LA , Francois Watkins LK . MMWR Morb Mortal Wkly Rep 2023 72 (45) 1225-1229 In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness. |
HIV and fungal priority pathogens
Sati H , Alastruey-Izquierdo A , Perfect J , Govender NP , Harrison TS , Chiller T , Sorrell TC , Bongomin F , Oladele R , Chakrabarti A , Wahyuningsih R , Colombo AL , Rodriguez-Tudela JL , Beyrer C , Ford N . Lancet HIV 2023 10 (11) e750-e754 The burden of invasive fungal infections associated with opportunistic fungal pathogens is a persistent challenge, particularly among people with advanced HIV disease. In October, 2022, WHO published the Fungal Priority Pathogens List (FPPL)-the first global effort to systematically prioritise fungal pathogens. Of the 19 pathogens in the WHO FPPL, four opportunistic pathogens in particular cause invasive diseases in people living with HIV: Cryptococcus neoformans, Histoplasma spp, Pneumocystis jirovecii, and Talaromyces marneffei. These four fungal pathogens are major causes of illness and death in people with advanced HIV and overwhelmingly affect those in low-income and middle-income countries. Access to diagnostics, improved surveillance, targeted support for innovation, and an enhanced public health focus on these diseases are needed in the effort to reduce HIV-associated deaths. |
Long COVID and significant activity limitation among adults, by age - United States, June 1-13, 2022, to June 7-19, 2023
Ford ND , Slaughter D , Edwards D , Dalton A , Perrine C , Vahratian A , Saydah S . MMWR Morb Mortal Wkly Rep 2023 72 (32) 866-870 Long COVID is a condition encompassing a wide range of health problems that emerge, persist, or return following COVID-19. CDC analyzed national repeat cross-sectional Household Pulse Survey data to estimate the prevalence of long COVID and significant related activity limitation among U.S. adults aged ≥18 years by age group. Data from surveys completed between June 1-13, 2022, and June 7-19, 2023, indicated that long COVID prevalence decreased from 7.5% (95% CI = 7.1-7.9) to 6.0% (95% CI = 5.7-6.3) among the overall U.S. adult population, irrespective of history of previous COVID-19, and from 18.9% (95% CI = 17.9-19.8) to 11.0% (95% CI = 10.4-11.6) among U.S. adults reporting previous COVID-19. Among both groups, prevalence decreased from June 1-13, 2022, through January 4-16, 2023, before stabilizing. When stratified by age, only adults aged <60 years experienced significant rates of decline (p<0.01). Among adults reporting previous COVID-19, prevalence decreased among those aged 30-79 years through fall or winter and then stabilized. During June 7-19, 2023, 26.4% (95% CI = 24.0-28.9) of adults with long COVID reported significant activity limitation, the prevalence of which did not change over time. These findings help guide the ongoing COVID-19 prevention efforts and planning for long COVID symptom management and future health care service needs. |
Prevalence of symptoms 12 months after acute illness, by COVID-19 testing status among adults - United States, December 2020-March 2023
Montoy JCC , Ford J , Yu H , Gottlieb M , Morse D , Santangelo M , O'Laughlin KN , Schaeffer K , Logan P , Rising K , Hill MJ , Wisk LE , Salah W , Idris AH , Huebinger RM , Spatz ES , Rodriguez RM , Klabbers RE , Gatling K , Wang RC , Elmore JG , McDonald SA , Stephens KA , Weinstein RA , Venkatesh AK , Saydah S . MMWR Morb Mortal Wkly Rep 2023 72 (32) 859-865 To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions. |
Epidemiology and antimicrobial resistance of Campylobacter infections in the United States, 2005-2018
Ford L , Healy JM , Cui Z , Ahart L , Medalla F , Ray LC , Reynolds J , Laughlin ME , Vugia DJ , Hanna S , Bennett C , Chen J , Rose EB , Bruce BB , Payne DC , Francois Watkins LK . Open Forum Infect Dis 2023 10 (8) ofad378 BACKGROUND: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. METHODS: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. RESULTS: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). CONCLUSIONS: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance. |
Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020 (preprint)
Shah MM , Salvatore PP , Ford L , Kamitani E , Whaley MJ , Mitchell K , Currie DW , Morgan CN , Segaloff HE , Lecher S , Somers T , Van Dyke ME , Bigouette JP , Delaney A , DaSilva J , O'Hegarty M , Boyle-Estheimer L , Abdirizak F , Karpathy SE , Meece J , Ivanic L , Goffard K , Gieryn D , Sterkel A , Bateman A , Kahrs J , Langolf K , Zochert T , Knight NW , Hsu CH , Kirking HL , Tate JE . medRxiv 2021 2021.04.05.21254834 Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Repeating antigen testing on the same day did not significantly improve test sensitivity while specificity remained high.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be made available upon reasonable request. |
Quantitative Comparison of SARS-CoV-2 Nucleic Acid Amplification Test and Antigen Testing Algorithms: A Decision Analysis Simulation Model (preprint)
Salvatore PP , Shah MM , Ford L , Delaney A , Hsu CH , Tate JE , Kirking HL . medRxiv 2021 2021.03.15.21253608 Background Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations continue to recommend different strategies for utilizing NAATs and antigen tests in various settings. There has not yet been a quantitative comparison of the expected performance of these strategies.Methods We utilized a decision analysis approach to simulate the expected outcomes of six algorithms for implementing NAAT and antigen testing, analogous to testing strategies recommended by public health organizations. Each algorithm was simulated 50,000 times for four SARS-CoV-2 infection prevalence levels ranging from 5% to 20% in a population of 100000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.Results Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Substituting repeat antigen testing in lieu of NAAT confirmation of all initial negative antigen tests resulted in 2,280 missed cases (95% UR: 1,507-3,067) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case at 10% prevalence compared to exclusive use of antigen tests.Conclusions No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities; each presents a trade-off between prioritized outcomes and resource constraints. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and constraints.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesCode for the algorithm simulations can be found on the CDC Epidemic Prediction Initiative GitHub site (https://github.com/cdcepi). |
Characteristics of children and antigen test performance at a SARS-CoV-2 community testing site (preprint)
Ford L , Whaley MJ , Shah MM , Salvatore PP , Segaloff HE , Delaney A , Currie DW , Boyle-Estheimer L , O'Hegarty M , Morgan CN , Meece J , Ivacic L , Thornburg NJ , Tamin A , Harcourt JL , Folster JM , Medrzycki M , Jain S , Wong P , Goffard K , Gieryn D , Kahrs J , Langolf K , Zochert T , Tate JE , Hsu CH , Kirking HL . medRxiv 2021 2021.07.06.21259792 Background Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture.Methods Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults.Results About one in ten included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR positive. Cycle threshold values were similar among RT-PCR positive specimens from children and adults (22.5 vs 21.3, p=0.46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, p=0.39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive value were 100% (27/27) and 94.9% (188/198) respectively. Virus was isolated from 51.4% (19/37) of RT-PCR positive pediatric specimens; all 19 had positive antigen test results.Conclusions With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request. |
A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex (preprint)
Muller-Schiffmann A , Michon M , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Muller L , Ostermann PN , Andree M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad MD , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . bioRxiv 2021 18 We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Recapitulation of Human Pathophysiology and Identification of Forensic Biomarkers in a Translational Swine Model of Chlorine Inhalation Injury (preprint)
Achanta S , Gentile MA , Albert CJ , Schulte KA , Pantazides BG , Crow BS , Quinones-Gonzalez J , Perez JW , Ford DA , Patel RP , Blake TA , Gunn MD , Jordt SE . bioRxiv 2022 10 Rationale: Chlorine gas (Cl<inf>2</inf>) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl<inf>2</inf> exposures frequently occur in domestic and occupational environments, and in transportation accidents. There is a knowledge gap in large animal models of Cl<inf>2</inf>-induced acute lung injury (ALI) required to accurately model human etiology and for the development of targeted countermeasures Objective: To develop a translational model of Cl<inf>2</inf>-induced ALI in swine to study toxicopathophysiology and identify biomarkers useful for forensic analysis. Method(s): Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl<inf>2</inf> gas (<= 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Result(s): Exposure to Cl<inf>2</inf> resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Chlorine exposure resulted in increased total BALF and neutrophil counts, vascular leakage, and edema compared to the control group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung after Cl<inf>2</inf>-exposure. Conclusion(s): The translational model developed in this study replicates key features of humans exposed to Cl<inf>2</inf> and is suitable to test medical countermeasures. Specific biomarkers of Cl<inf>2</inf> exposure have been identified in plasma and lung tissue samples. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Mixtures of urinary concentrations of phenols and phthalate biomarkers in relation to the ovarian reserve among women attending a fertility clinic
Génard-Walton M , McGee G , Williams PL , Souter I , Ford JB , Chavarro JE , Calafat AM , Hauser R , Mínguez-Alarcón L . Sci Total Environ 2023 898 165536 Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004-2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = -0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts. |
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