Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 204 Records) |
Query Trace: Coleman C [original query] |
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Persistent endocrine-disrupting chemicals and incident uterine leiomyomata: A mixtures analysis
Wesselink AK , Claus Henn B , Fruh V , Geller RJ , Coleman CM , Schildroth S , Sjodin A , Bethea TN , Noel NL , Baird DD , Wegienka G , Wise LA . Sci Total Environ 2024 951 175871 BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL. METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders. RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (β comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (β for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (β = -0.06, 95 % CrI: -0.21, 0.10 and β = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs. CONCLUSION: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions. |
Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice
Karaaslan E , Sorvillo TE , Scholte FEM , O'Neal TJ , Welch SR , Davies KA , Coleman-McCray JD , Harmon JR , Ritter JM , Pegan SD , Montgomery JM , Spengler JR , Spiropoulou CF , Bergeron É . NPJ Vaccines 2024 9 (1) 148 Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals. |
Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study
Wise LA , Coleman CM , Schildroth S , Geller RJ , Lovett SM , Claus Henn B , Calafat AM , Botelho JC , Marsh EE , Noel N , Wegienka GR , Bethea TN , Harmon QE , Baird DD , Wesselink AK . J Expo Sci Environ Epidemiol 2024 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. IMPACT STATEMENT: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development. |
Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus
Sorvillo TE , Karaaslan E , Scholte FEM , Welch SR , Coleman-McCray JD , Genzer SC , Ritter JM , Hayes HM , Jain S , Pegan SD , Bergeron É , Montgomery JM , Spiropoulou CF , Spengler JR . NPJ Vaccines 2024 9 (1) 88 Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar(-/-) mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar(-/-) mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection. |
Predictors of PrEP retention and attrition in an urban publicly funded safety-net specialty clinic
Drezner K , Coleman M , Visconti A , Thomas C , Beverley J , Harold RE , Furness BW . AIDS Behav 2024 Pre-exposure prophylaxis (PrEP) is an effective tool for human immunodeficiency virus (HIV) prevention. The purpose of this study is to identify correlates of PrEP retention using patient data from an urban, publicly funded safety-net clinic in Washington, DC. Cox proportional hazards regression, logistical regression, and survival curves were used to assess the association of age, gender, race/ethnicity, insurance, number of partners, and sexually transmitted infection (STI) diagnosis at PrEP initiation with time on PrEP. From August 2016-December 2020, 1,126 people were prescribed PrEP - patients were mostly Black (44.8%) or Latinx (30.4%) and identified as cisgender men (84.6%). Half had no insurance (49.1%), with the remaining patients reporting private (28.9%) or public (21.5%) insurance. Age at PrEP prescription ranged from 15 to 66 with 80% being 20 to 39 years. For the 87.7% (n = 987) of patients who discontinued PrEP, mean PrEP time was 158 days and median was 28 days. The highest rates of discontinuation were observed within the first month with 44.3% discontinuing by day 30, 52.3% by 3 months, and 73.2% by 1 year. Cisgender women, transgender persons, and those younger than 30 years were more likely to discontinue PrEP. Latinx and patients with less than 3 male partners in the last 90 days were less likely to discontinue PrEP. We demonstrated a high level of PrEP uptake among populations disproportionally affected by HIV. Future analyses are needed to examine ways of reducing barriers to PrEP initiation and improving PrEP adherence. |
A prospective cohort study of persistent endocrine disrupting chemicals and perceived stress
Schildroth S , Wesselink AK , Bethea TN , Henn BC , Friedman A , Fruh V , Coleman CM , Lovett SM , Vines AI , Sjodin A , Botelho JC , Calafat AM , Wegienka G , Weuve J , Baird DD , Wise LA . Am J Epidemiol 2024 Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women. |
Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model
Scholte FEM , Spengler JR , Welch SR , Harmon JR , Coleman-McCray JD , Davies KA , Pegan SD , Montgomery JM , Spiropoulou CF , Bergeron É . Virus Res 2024 345 199398 Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ovarian tumor (OTU) domain with a cysteine protease thought to modulate cellular immune responses by removing ubiquitin and ISG15 post-translational modifications from host and viral proteins. Viral deubiquitinases like CCHFV OTU are attractive drug targets, as blocking their activity may enhance cellular immune responses to infection, and potentially inhibit viral replication itself. We previously demonstrated that the engineered ubiquitin variant CC4 is a potent inhibitor of CCHFV replication in vitro. A major challenge of the therapeutic use of small protein inhibitors such as CC4 is their requirement for intracellular delivery, e.g., by viral vectors. In this study, we examined the feasibility of in vivo CC4 delivery by a replication-deficient recombinant adenovirus (Ad-CC4) in a lethal CCHFV mouse model. Since the liver is a primary target of CCHFV infection, we aimed to optimize delivery to this organ by comparing intravenous (tail vein) and intraperitoneal injection of Ad-CC4. While tail vein injection is a traditional route for adenovirus delivery, in our hands intraperitoneal injection resulted in higher and more widespread levels of adenovirus genome in tissues, including, as intended, the liver. However, despite promising in vitro results, neither route of in vivo CC4 treatment resulted in protection from a lethal CCHFV infection. |
Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women
Schildroth S , Henn BC , Vines AI , Geller RJ , Lovett SM , Coleman CM , Bethea TN , Botelho JC , Calafat AM , Milando C , Baird DD , Wegienka G , Wise LA . Sci Total Environ 2024 172445 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms in women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify PFAS effects on other health outcomes. OBJECTIVE: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. METHODS: We analyzed data from 1499 participants (23-35 years) from the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. RESULTS: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (β = 0.03; 95 % CI = 0.20, 0.25), 50th (β = 0.02; 95 % CI = -0.16, 0.19), and 90th (β = 0.01; 95 % CI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify PFAS mixture. CONCLUSION: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress. |
Effect of adopting a Timothy Hay-Based Diet at weaning or in adulthood on urinary tract parameters in strain 13/n guinea pigs (Cavia porcellus)
Wier RC , Flietstra TD , Coleman-McCray JD , Genzer SC , Brake ME , Velazquez EM , Forero C , Welch SR , Tansey CM , Condrey JA , Spengler JR . J Am Assoc Lab Anim Sci 2024 Type of feed is an important consideration in herbivore colony management, yet limited studies report on the effects of diet on common conditions such as urolithiasis in guinea pigs. Urolithiasis is a well-documented cause of lower urinary tract disease in guinea pigs, with calcium carbonate uroliths reported as the predominant calculi formed in the guinea pig urinary tract. A calcium-rich diet has been suggested as a risk factor for of urolithiasis, with numerous commercially available guinea pig diets formulated for adults avoiding ingredients that are higher in calcium. Due to the high incidence of urolithiasis in our strain 13/N guinea pig colony, we conducted a prospective control study following the implementation of dietary changes aimed at improving overall urinary tract health and reducing risk factors for urolithiasis, thus improving colony welfare. A control group was kept on the original ad libitum alfalfa hay-based pellet diet with restricted loose timothy hay (control diet, 14 juveniles and 24 adults). An experimental group was placed on a portioned, 1 oz daily, timothy hay-based pellet diet with ad libitum loose timothy hay (experimental diet, 21 juveniles and 23 adults). Juveniles and adults were followed for a total of 14 and 26 wk, respectively. Longitudinal blood and urine samples were collected to evaluate blood chemistry and urinary parameters, along with weight and body condition scores to assess general health. Overall, dietary changes did not improve parameters associated with improved urinary tract health or reduced risk of urolithiasis; feeding strategy was not found to meaningfully affect calcium crystalluria, urine protein, urine specific gravity, or renal values. These data support alfalfa hay-based pellet or timothy hay-based pellet, when fed with loose timothy hay, as viable options and suggest that practices aimed at reducing dietary calcium by reducing pelleted diet portions are insufficient to mitigate risk factors for urolithiasis in guinea pigs. |
Peripheral immune responses to filoviruses in a reservoir versus spillover hosts reveal transcriptional correlates of disease
Guito JC , Arnold CE , Schuh AJ , Amman BR , Sealy TK , Spengler JR , Harmon JR , Coleman-McCray JD , Sanchez-Lockhart M , Palacios GF , Towner JS , Prescott JB . Front Immunol 2023 14 1306501 Several filoviruses, including Marburg virus (MARV), cause severe disease in humans and nonhuman primates (NHPs). However, the Egyptian rousette bat (ERB, Rousettus aegyptiacus), the only known MARV reservoir, shows no overt illness upon natural or experimental infection, which, like other bat hosts of zoonoses, is due to well-adapted, likely species-specific immune features. Despite advances in understanding reservoir immune responses to filoviruses, ERB peripheral blood responses to MARV and how they compare to those of diseased filovirus-infected spillover hosts remain ill-defined. We thus conducted a longitudinal analysis of ERB blood gene responses during acute MARV infection. These data were then contrasted with a compilation of published primate blood response studies to elucidate gene correlates of filovirus protection versus disease. Our work expands on previous findings in MARV-infected ERBs by supporting both host resistance and disease tolerance mechanisms, offers insight into the peripheral immunocellular repertoire during infection, and provides the most direct known cross-examination between reservoir and spillover hosts of the most prevalently-regulated response genes, pathways and activities associated with differences in filovirus pathogenesis and pathogenicity. |
Characterization of humoral responses to Nipah virus infection in the Syrian Hamster model of disease
Scholte FEM , Rodriguez SE , Welch SR , Davies KA , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Lo MK , Karaaslan E , Bergeron E , Montgomery JM , Spengler JR , Spiropoulou CF . J Infect Dis 2023 Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose. |
Impact of state stroke systems of care laws on stroke outcomes
Fulmer EB , Keener Mast D , Godoy Garraza L , Gilchrist S , Rasool A , Xu Y , Brown A , Omeaku N , Ye Z , Donald B , Shantharam S , Coleman King S , Popoola A , Cincotta K . Healthcare (Basel) 2023 11 (21) Since 2003, 38 US states and Washington, DC have adopted legislation and/or regulations to strengthen stroke systems of care (SSOCs). This study estimated the impact of SSOC laws on stroke outcomes. We used a coded legal dataset of 50 states and DC SSOC laws (years 2003-2018), national stroke accreditation information (years 1997-2018), data from the Healthcare Cost and Utilization Project (years 2012-2018), and National Vital Statistics System (years 1979-2019). We applied a natural experimental design paired with longitudinal modeling to estimate the impact of having one or more SSOC policies in effect on outcomes. On average, states with one or more SSOC policies in effect achieved better access to primary stroke centers (PSCs) than expected without SSOC policies (ranging from 2.7 to 8.0 percentage points (PP) higher), lower inpatient hospital costs (USD 610-1724 less per hospital stay), lower age-adjusted stroke mortality (1.0-1.6 fewer annual deaths per 100,000), a higher proportion of stroke patients with brain imaging results within 45 min of emergency department arrival (3.6-5.0 PP higher), and, in some states, lower in-hospital stroke mortality (5 fewer deaths per 1000). Findings were mixed for some outcomes and there was limited evidence of model fit for others. No effect was observed in racial and/or rural disparities in stroke mortality. |
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
Optimal reference genes for RNA tissue analysis in small animal models of hemorrhagic fever viruses
Davies KA , Welch SR , Sorvillo TE , Coleman-McCray JD , Martin ML , Brignone JM , Montgomery JM , Spiropoulou CF , Spengler JR . Sci Rep 2023 13 (1) 19384 Reverse-transcription quantitative polymerase chain reaction assays are frequently used to evaluate gene expression in animal model studies. Data analyses depend on normalization using a suitable reference gene (RG) to minimize effects of variation due to sample collection, sample processing, or experimental set-up. Here, we investigated the suitability of nine potential RGs in laboratory animals commonly used to study viral hemorrhagic fever infection. Using tissues (liver, spleen, gonad [ovary or testis], kidney, heart, lung, eye, brain, and blood) collected from naïve animals and those infected with Crimean-Congo hemorrhagic fever (mice), Nipah (hamsters), or Lassa (guinea pigs) viruses, optimal species-specific RGs were identified based on five web-based algorithms to assess RG stability. Notably, the Ppia RG demonstrated stability across all rodent tissues tested. Optimal RG pairs that include Ppia were determined for each rodent species (Ppia and Gusb for mice; Ppia and Hrpt for hamsters; and Ppia and Gapdh for guinea pigs). These RG pair assays were multiplexed with viral targets to improve assay turnaround time and economize sample usage. Finally, a pan-rodent Ppia assay capable of detecting Ppia across multiple rodent species was developed and successfully used in ecological investigations of field-caught rodents, further supporting its pan-species utility. |
Per- and polyfluoroalkyl substances and anti-müllerian hormone concentrations in two preconception cohort studies
Wise LA , Wang TR , Mikkelsen EM , Wesselink AK , Calafat AM , Wegienka G , Geller RJ , Coleman CM , Willis MD , Marsh EE , Schildroth S , Botelho JC , Messerlian-Lambert G , Hatch EE . Environ Health Perspect 2023 131 (10) 107703 Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent synthetic chemicals found in consumer products, firefighting foam, and contaminated food and water.1 Routes of exposure include ingestion, inhalation, and dermal absorption.1 Several PFAS have long biological half-lives and can bioaccumulate in living organisms.2 Although the prevalence of commonly manufactured PFAS in the United States has decreased since 2000 following phase-outs and chemical substitutions, their detection in humans remains high.1 | | PFAS can cross the blood–follicle barrier and have been detected in follicular fluid.3 Greater serum PFAS concentrations have been associated with irregular menses, longer menstrual cycles, lower estradiol and progesterone concentrations, and premature ovarian insufficiency.3 Greater concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA) have been associated with reduced fertility,4 though results vary by study design and parity. For example, most retrospective studies showed inverse associations between PFOA and fertility, whereas most prospective studies did not4; some showed inverse associations among nulliparous participants only.4 |
Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies
Hollister J , Caban-Martinez AJ , Ellingson KD , Beitel S , Fowlkes AL , Lutrick K , Tyner H , Naleway AL , Yoon SK , Gaglani M , Hunt D , Meece J , Mayo Lamberte J , Schaefer Solle N , Rose S , Dunnigan K , Khan SM , Kuntz JL , Fisher JM , Coleman A , Britton A , Thiese M , Hegmann K , Pavuk M , Ramadan F , Fuller S , Nematollahi A , Sprissler R , Burgess JL . Environ Res 2023 239 117297 Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination. |
Sodium and potassium consumption in Jamaica: National estimates and associated factors from the Jamaica Health and Lifestyle Survey 2016-2017
Ferguson TS , Younger-Coleman NOM , Webster-Kerr K , Tulloch-Reid MK , Bennett NR , Davidson T , Grant AS , Gordon-Johnson KM , Govia I , Soares-Wynter S , McKenzie JA , Walker E , Cunningham-Myrie CA , Anderson SG , Blake AL , Ho J , Stephenson R , Edwards SE , McFarlane SR , Spence S , Wilks RJ . Medicine (Baltimore) 2023 102 (40) e35308 This study aimed to estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. A cross-sectional study was conducted using data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were noninstitutionalized Jamaicans aged ≥15 years. Trained staff collected sociodemographic and health data via interviewer-administered questionnaires and spot urine samples. The Pan American Health Organization formula was used to estimate 24-hour urine sodium and potassium excretion. High sodium level was defined as ≥2000 mg/day, and low potassium levels as <3510 mg/day (World Health Organization criteria). Associations between these outcomes and sociodemographic and clinical characteristics were explored using multivariable ANOVA models using log-transformed 24-hour urine sodium and potassium as outcome variables. Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). The mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, P < .001). The mean potassium excretion was 2052 mg/day (males, 2210 mg/day; females, 1904 mg/day; P = .001). The prevalence of high sodium consumption was 66.6% (males 72.8%, females 60.7%, P < .001) and that of low potassium intake was 88.8% (85.1% males, 92.3% females, P < .001). Sodium consumption was inversely associated with older age, higher education, and low glomerular filtration rate but was directly associated with being male, current smoking, and obesity. Overall, males had higher sodium consumption than women, with the effect being larger among hypertensive men. Women with hypertension had lower sodium consumption than nonhypertensive women; however, hypertensive men had higher sodium consumption than nonhypertensive men. Potassium consumption was higher among men, persons with obesity, and those with high total cholesterol but was lower among men with "more than high school" education compared to men with "less than high school" education. We conclude that most Jamaican adults have diets high in sodium and low in potassium. In this study, sodium consumption was directly associated with male sex, obesity, and current smoking but was inversely associated with older age and higher education. High potassium consumption was associated with obesity and high cholesterol levels. These associations should be further explored in longitudinal studies and population-based strategies should be developed to address these cardiovascular risk factors. |
Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals
Otter AD , Jones S , Hicks B , Bailey D , Callaby H , Houlihan C , Rampling T , Gordon NC , Selman H , Satheshkumar PS , Townsend M , Mehta R , Pond M , Jones R , Wright D , Oeser C , Tonge S , Linley E , Hemingway G , Coleman T , Millward S , Lloyd A , Damon I , Brooks T , Vipond R , Rowe C , Hallis B . Nat Commun 2023 14 (1) 5948 In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design. |
Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions
Scholte FEM , Karaaslan E , O'Neal TJ , Sorvillo TE , Genzer SC , Welch SR , Coleman-McCray JD , Spengler JR , Kainulainen MH , Montgomery JM , Pegan SD , Bergeron E , Spiropoulou CF . Front Cell Infect Microbiol 2023 13 1233148 Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine's efficacy. |
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Welch SR , Spengler JR , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Scholte FEM , Rodriguez SE , O'Neal TJ , Ritter JM , Ficarra G , Davies KA , Kainulainen MH , Karaaslan E , Bergeron É , Goldsmith CS , Lo MK , Nichol ST , Montgomery JM , Spiropoulou CF . Sci Adv 2023 9 (31) eadh4057 Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease. |
Impact of Diabetes Status on Immunogenicity of Trivalent Inactivated Influenza Vaccine in Older Adults (preprint)
Spencer S , Chung JR , Belongia EA , Sundaram M , Meece J , Coleman LA , Zimmerman RK , Nowalk MP , Moehling Geffel K , Ross T , Carter CE , Shay D , Levine M , Liepkalns J , Kim JH , Sambhara S , Thompson MG , Flannery B . medRxiv 2021 2021.10.04.21264429 Individuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50-80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold-increases in antibody titer occurred among individuals with lower pre-vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status.Competing Interest StatementKKM, MPN and RZ have received research funds from Merck & Co., Inc and Pfizer, Inc. KKM and RZ have received research funds from Sanofi Pasteur, Inc. LC is currently employed by Novartis. The remaining authors report no conflicts of interest.Funding StatementThis study was supported by cooperative agreements U01 IP000471 and U01 IP000467 from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of those authors and do not necessarily represent the views of 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:Institutional Review Boards at the University of Pittsburgh and Marshfield Clinic approved this study.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 are not publicly available at this time. |
Sodium and Potassium Consumption in Jamaica: National Estimates and Associated Factors from the Jamaica Health and Lifestyle Survey 2016-2017 (preprint)
Ferguson TS , Younger-Coleman NOM , Webster-Kerr K , Tulloch-Reid MK , Bennett NR , Davidson T , Grant AS , Gordon-Johnson KAM , Govia I , Soares-Wynter S , McKenzie JA , Walker E , Cunningham-Myrie CA , Anderson SG , Blake AL , Ho J , Stephenson R , Edwards SE , McFarlane SR , Spence S , Wilks RJ . medRxiv 2023 19 Objective: To estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. Method(s): We conducted a cross-sectional analysis of data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were non-institutionalized Jamaicans, >=15 years. Trained staff collected sociodemographic and health data via interviewer administered questionnaires and collected spot urine samples. The Pan American Health Organization Formulae were used to estimate 24-hour urine sodium and potassium excretion. High sodium was defined as >=2000 mg/day and low potassium as <3510 mg/day (World Health Organization criteria). Associations of these outcomes with sociodemographic and clinical characteristics were explored in sex specific multivariable ANOVA models. Result(s): Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). Mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, p<0.001). Mean potassium excretion was 2052 mg/day (males 2210 mg/day, females 1904 mg/day, p=0.001). The prevalence of high sodium consumption was 66.6% (males 72.8%, female 60.7%, p<0.001) and low potassium intake was 88.8% (85.1% males, 92.3% females, p<0.001). Among males, sodium consumption was inversely associated with older age and prehypertension, but directly associated with current smoking and obesity. Among females, sodium consumption was inversely associated with hypertension, impaired fasting glucose, low GFR and high physical activity, but was directly associated with obesity. Conclusion(s): Most Jamaican adults have diets high in sodium and low in potassium. Sodium consumption was directly associated with obesity in both men and women. Population based strategies are therefore required to address these cardiovascular risk factors. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Estimating malaria transmission risk through surveillance of human-vector interactions in northern Ghana
Coleman S , Yihdego Y , Gyamfi F , Kolyada L , Tongren JE , Zigirumugabe S , Dery DB , Badu K , Obiri-Danso K , Boakye D , Szumlas D , Armistead JS , Dadzie SK . Parasit Vectors 2023 16 (1) 205 BACKGROUND: Vector bionomics are important aspects of vector-borne disease control programs. Mosquito-biting risks are affected by environmental, mosquito behavior and human factors, which are important for assessing exposure risk and intervention impacts. This study estimated malaria transmission risk based on vector-human interactions in northern Ghana, where indoor residual spraying (IRS) and insecticide-treated nets (ITNs) have been deployed. METHODS: Indoor and outdoor human biting rates (HBRs) were measured using monthly human landing catches (HLCs) from June 2017 to April 2019. Mosquitoes collected were identified to species level, and Anopheles gambiae sensu lato (An. gambiae s.l.) samples were examined for parity and infectivity. The HBRs were adjusted using mosquito parity and human behavioral observations. RESULTS: Anopheles gambiae was the main vector species in the IRS (81%) and control (83%) communities. Indoor and outdoor HBRs were similar in both the IRS intervention (10.6 vs. 11.3 bites per person per night [b/p/n]; z = -0.33, P = 0.745) and control communities (18.8 vs. 16.4 b/p/n; z = 1.57, P = 0.115). The mean proportion of parous An. gambiae s.l. was lower in IRS communities (44.6%) than in control communities (71.7%). After adjusting for human behavior observations and parity, the combined effect of IRS and ITN utilization (IRS: 37.8%; control: 57.3%) on reducing malaria transmission risk was 58% in IRS + ITN communities and 27% in control communities with ITNs alone (z = -4.07, P < 0.001). However, this also revealed that about 41% and 31% of outdoor adjusted bites in IRS and control communities respectively, occurred before bed time (10:00 pm). The mean directly measured annual entomologic inoculation rates (EIRs) during the study were 6.1 infective bites per person per year (ib/p/yr) for IRS communities and 16.3 ib/p/yr for control communities. After considering vector survival and observed human behavior, the estimated EIR for IRS communities was 1.8 ib/p/yr, which represents about a 70% overestimation of risk compared to the directly measured EIR; for control communities, it was 13.6 ib/p/yr (16% overestimation). CONCLUSION: Indoor residual spraying significantly impacted entomological indicators of malaria transmission. The results of this study indicate that vector bionomics alone do not provide an accurate assessment of malaria transmission exposure risk. By accounting for human behavior parameters, we found that high coverage of ITNs alone had less impact on malaria transmission indices than combining ITNs with IRS, likely due to observed low net use. Reinforcing effective communication for behavioral change in net use and IRS could further reduce malaria transmission. |
Population-based cancer survival in Canada and the United States by socioeconomic status: Findings from the CONCORD-2 Study
Weir HK , Bryant H , Turner D , Coleman MP , Mariotto AB , Spika D , Matz M , Harewood R , Tucker TC , Allemani C . J Registry Manag 2022 49 (1) 23-33 BACKGROUND: Population-based cancer survival provides insight into the effectiveness of health systems to care for all residents with cancer, including those in marginalized groups. METHODS: Using CONCORD-2 data, we estimated 5-year net survival among patients diagnosed 2004-2009 with one of 10 common cancers, and children diagnosed with acute lymphoblastic leukemia (ALL), by socioeconomic status (SES) quintile, age (0-14, 15-64, ≥65 years), and country (Canada or United States). RESULTS: In the lowest SES quintile, survival was higher among younger Canadian adults diagnosed with liver (23% vs 15%) and cervical (78% vs 68%) cancers and with leukemia (62% vs 56%), including children diagnosed with ALL (92% vs 86%); and higher among older Americans diagnosed with colon (62% vs 56%), female breast (87% vs 80%), and prostate (97% vs 85%) cancers. In the highest SES quintile, survival was higher among younger Americans diagnosed with stomach cancer (33% vs 27%) and younger Canadians diagnosed with liver cancer (31% vs 23%); and higher among older Americans diagnosed with stomach (27% vs 22%) and prostate (99% vs 92%) cancers. CONCLUSIONS: Among younger Canadian cancer patients in the lowest SES group, greater access to health care may have resulted in higher cancer survival, while higher screening prevalence and access to health insurance (Medicare) among older Americans during the period of this study may have resulted in higher survival for some screen-detected cancers. Higher survival in the highest SES group for stomach and liver may relate to treatment differences. Survival differences by age and SES between Canada and the United States may help inform cancer control strategies. |
Fluorescent and bioluminescent reporter mouse-adapted Ebola viruses maintain pathogenicity and can be visualized in vivo
Davies KA , Welch SR , Jain S , Sorvillo TE , Coleman-McCray JD , Montgomery JM , Spiropoulou CF , Albariño C , Spengler JR . J Infect Dis 2023 228 S536-S547 Ebola virus (EBOV) causes lethal disease in humans but not in mice. Here, we generated recombinant mouse-adapted (MA)-EBOVs, including one based on the previously reported serially adapted strain (rMA-EBOV), along with single-reporter rMA-EBOVs expressing either fluorescent (ZsGreen1 [ZsG]) or bioluminescent (nano-luciferase [nLuc]) reporters, and dual-reporter rMA-EBOVs expressing both ZsG and nLuc. No detriment to viral growth in vitro was seen with inclusion of MA-associated mutations or reporter proteins. In CD-1 mice, infection with MA-EBOV, rMA-EBOV, and single-reporter rMA-EBOVs conferred 100% lethality; infection with dual-reporter rMA-EBOV resulted in 80% lethality. Bioluminescent signal from rMA-EBOV expressing nLuc was detected in vivo and ex vivo using the IVIS Spectrum CT. Fluorescent signal from rMA-EBOV expressing ZsG was detected in situ using hand-held blue-light transillumination and ex vivo through epi-illumination with the IVIS Spectrum CT. These data support the use of reporter MA-EBOV for studies of Ebola virus in animal disease models. |
Response to letters-to-the-editor for publication: "Defect-free care trends in the Paul Coverdell National Acute Stroke Program (PCNASP), 2008-2018. American Heart Journal. 2021;232:177-184. doi:10.1016/j.ahj.2020.11.010."
Overwyk K , Yin X , Tong X , Coleman King SM , Wiltz JL . Am Heart J 2021 236 112 Thank you for your letter. We recognize that stroke-related laws, policies, and funding vary by state, which impacts the provision of stroke care. Centers for disease control and prevention (CDC’s) Division for Heart Disease and Stroke Prevention has posted resources on stroke-related state policy and capacity at https://www.cdc.gov/dhdsp/pubs/stroke_resources.htm. We also recently published a report1 on evidence-supported state laws to advance stroke care. State-level data from nine funded states drive the Paul Coverdell National Acute Stroke Program’s (PCNASP’s) activities. For example, each PCNASP state receives quarterly reports on its quality improvement activities, and state summaries for each funding cycle and state success stories are shared publicly.2, 3 | | We appreciate Steven Thomas’s comment about evaluating stroke care during the current pandemic. PCNASP’s support for data collection to improve the quality of stroke care in its nine funded states is ongoing through the pandemic and into the future.4, 5 Additionally, national dissemination of the funded states’ successes helps extend these lessons beyond the Coverdell experience. |
Effect of parental age, parity, and pairing approach on reproduction in strain 13/N guinea pigs (Cavia porcellus)
Genzer SC , Flietstra T , Coleman-McCray JD , Tansey C , Welch SR , Spengler JR . Animals 2023 13 (5) Guinea pigs are important animal models for human disease, and both outbred and inbred lines are utilized in biomedical research. The optimal maintenance of guinea pig colonies, commercially and in research settings, relies on robust informed breeding programs, however, breeding data on specialized inbred strains are limited. Here, we investigated the effects of parental age, parity, and pairing approaches on mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days in strain 13/N guinea pigs. Our analysis of colony breeding data indicates that the average litter size is 3.3 pups, with a 25.2% stillbirth rate, a failure-to-thrive outcome in 5.1% of pups, and a 10 day survival rate of 69.7%. The only variable to significantly affect the reproductive outcomes examined was parental age (p < 0.05). In comparison to adults, both juvenile and geriatric sows had lower total fetus counts; juvenile boars had a higher percentage of females in litters, and geriatric boars had a lower 10 day survival rate of pups. These studies provide valuable information regarding the reproductive characteristics of strain 13/N guinea pigs, and support a variety of breeding approaches without significant effects on breeding success. |
Mouse models of Ebola virus tolerance and lethality: Characterization of CD-1 mice infected with wild-type, guinea pig-adapted, or mouse-adapted variants
Spengler JR , Welch SR , Ritter JM , Harmon JR , Coleman-McCray JD , Genzer SC , Nascimento Seixas J , Scholte FEM , Davies KA , Bradfute SB , Montgomery JM , Spiropoulou CF . Antiviral Res 2022 210 105496 Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) variants in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV results in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant does not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice, supporting use of these models of virus tolerance for continued investigations of non-lethal infection and sequelae. |
Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease
Welch SR , Ritter JM , Schuh AJ , Genzer SC , Sorvillo TE , Harmon JR , Coleman-McCray JD , Jain S , Shrivastava-Ranjan P , Seixas JN , Estetter LB , Fair PS , Towner JS , Montgomery JM , Albariño CG , Spiropoulou CF , Spengler JR . Antiviral Res 2022 209 105490 Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues. |
Leveraging informatics to improve environmental health practice and innovation
Coleman EW , Jagne AF , Ruiz AJ . J Environ Health 2022 85 (4) 44-46 Environmental health professionals are embracing informatics as a tool to improve the health of populations across the nation. It is essential to ensure the public has access to environmental health-related data, such as restaurant and recreational water inspections, to help make informed decisions about health and safety. While many environmental health programs across the country share their data using online platforms, this practice is not universal and the timeliness, ease of access, and extent of data sharing vary across programs. | | The Centers for Disease Control and Prevention partnered with the Public Health Informatics Institute to better understand how environmental health programs collect and share data. This month's column highlights the information gathered from key informants to provide insight into data standardization. |
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