Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 139 Records) |
Query Trace: Ding M[original query] |
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Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.
Cui A , Zhu Z , Chen M , Zheng H , Liu L , Wang Y , Ma Y , Wang C , Fang X , Li P , Guan R , Wang S , Zhou J , Zheng L , Gao H , Ding Z , Li L , Bo F , Sun Z , Zhang Z , Feng D , He J , Chen H , Jin L , Rota PA , Xu W . Infect Genet Evol 2014 21 384-90 The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China. |
Large-scale validation of skin prion seeding activity as a biomarker for diagnosis of prion diseases
Zhang W , Orrú CD , Foutz A , Ding M , Yuan J , Shah SZA , Zhang J , Kotobelli K , Gerasimenko M , Gilliland T , Chen W , Tang M , Cohen M , Safar J , Xu B , Hong DJ , Cui L , Hughson AG , Schonberger LB , Tatsuoka C , Chen SG , Greenlee JJ , Wang Z , Appleby BS , Caughey B , Zou WQ . Acta Neuropathol 2024 147 (1) 17 Definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) relies on the examination of brain tissues for the pathological prion protein (PrP(Sc)). Our previous study revealed that PrP(Sc)-seeding activity (PrP(Sc)-SA) is detectable in skin of sCJD patients by an ultrasensitive PrP(Sc) seed amplification assay (PrP(Sc)-SAA) known as real-time quaking-induced conversion (RT-QuIC). A total of 875 skin samples were collected from 2 cohorts (1 and 2) at autopsy from 2-3 body areas of 339 cases with neuropathologically confirmed prion diseases and non-sCJD controls. The skin samples were analyzed for PrP(Sc)-SA by RT-QuIC assay. The results were compared with demographic information, clinical manifestations, cerebrospinal fluid (CSF) PrP(Sc)-SA, other laboratory tests, subtypes of prion diseases defined by the methionine (M) or valine (V) polymorphism at residue 129 of PrP, PrP(Sc) types (#1 or #2), and gene mutations in deceased patients. RT-QuIC assays of the cohort #1 by two independent laboratories gave 87.3% or 91.3% sensitivity and 94.7% or 100% specificity, respectively. The cohort #2 showed sensitivity of 89.4% and specificity of 95.5%. RT-QuIC of CSF available from 212 cases gave 89.7% sensitivity and 94.1% specificity. The sensitivity of skin RT-QuIC was subtype dependent, being highest in sCJDVV1-2 subtype, followed by VV2, MV1-2, MV1, MV2, MM1, MM1-2, MM2, and VV1. The skin area next to the ear gave highest sensitivity, followed by lower back and apex of the head. Although no difference in brain PrP(Sc)-SA was detected between the cases with false negative and true positive skin RT-QuIC results, the disease duration was significantly longer with the false negatives [12.0 ± 13.3 (months, SD) vs. 6.5 ± 6.4, p < 0.001]. Our study validates skin PrP(Sc)-SA as a biomarker for the detection of prion diseases, which is influenced by the PrP(Sc) types, PRNP 129 polymorphisms, dermatome sampled, and disease duration. |
Investigating the associations between socioeconomic factors and unhealthy days among adults using zero-inflated negative binomial regression
Liu J , Jiang N , Fan AZ , Thompson WW , Ding R , Ni S . SAGE Open 2023 13 (3) Poor social and economic circumstances affect the health of individuals throughout the life cycle. The purpose of the study was to examine whether state-level and individual-level socioeconomic factors are associated with mentally or physically unhealthy days in the general U.S. population of adults. The Behavioral Risk Factor Surveillance System and the American Community Survey in 2016 were used to examine state-level social determinants of health and the number of self-reported mentally unhealthy days in the last 30 days using Zero-Inflated Negative Binomial (ZINB) regression models. Men, older individuals, minorities, persons with higher educational attainment levels, persons who were employed, persons who were married, or with a partner, and persons with one or zero chronic condition were more likely to report excessive zeros for responses to the mentally, and physically unhealthy days. The negative binomial regression results indicated that higher state-level poverty rates, higher income inequity, lower median income, and higher unemployment rates were related to the higher number of reported mentally, and physically unhealthy days. Persons with higher educational attainment, and who were employed reported lower mentally, and physically unhealthy days. The findings show significant relationships between socioeconomic contexts and general health status. Health planners and policymakers may use the results to allocate resources and guide public policies and programs. © The Author(s) 2023. |
Per- and polyfluoroalkyl substances (PFAS) and lipid trajectories in women 45-56 years of age: The study of women's health across the nation
Kang H , Ding N , Karvonen-Gutierrez CA , Mukherjee B , Calafat AM , Park SK . Environ Health Perspect 2023 131 (8) 87004 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with less favorable blood lipid profiles in epidemiological studies. However, little is known about the potential role of PFAS in longitudinal changes in lipids among midlife women even though women become more susceptible to metabolic alterations during the menopausal transition. OBJECTIVES: To examine associations of serum PFAS concentrations with longitudinal trajectories of blood total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in midlife women undergoing menopausal transition. METHODS: The sample included 1,130 women from the Study of Women's Health Across the Nation 45-56 y of age at baseline (1999-2000). We measured serum PFAS concentrations including linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), linear and branched perfluorooctanesulfonic acid (n-PFOS and Sm-PFOS, respectively), and perfluorohexanesulfonic acid (PFHxS) at baseline. We used k-means clustering to identify subgroups with different patterns of PFAS mixture. Blood lipids were measured annually or biannually through 2016 with an average follow-up of 14.8 y. We identified longitudinal trajectories of each lipid using latent class growth models. We used multinomial log-linear models adjusted for covariates to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of lipid trajectory classes by PFAS and their mixtures. RESULTS: Three distinct trajectories (low, middle, high) of total, LDL, and HDL cholesterol and two distinct trajectories (low and high) of triglycerides were identified. n-PFOS, Sm-PFOS, and PFHxS were positively associated with total and LDL cholesterol trajectories. n-PFOS was inversely associated with triglycerides trajectories. PFAS mixtures (high vs. low) showed positive associations with total and LDL cholesterol trajectories (high vs. low), showing ORs (95% CIs) of 1.69 (95% CI: 1.36, 2.12) and 1.79 (95% CI: 1.44, 2.22), respectively. DISCUSSION: Concentrations of serum PFAS were positively associated with trajectories of total and LDL cholesterol, providing a line of evidence supporting adverse effects of PFAS on lipid homeostasis. https://doi.org/10.1289/EHP12351. |
Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Mucosal and systemic neutralizing antibodies to norovirus and rotavirus by oral immunization with recombinant rotavirus in infant mice (preprint)
Kawagishi T , Sanchez-Tacuba L , Feng N , Costantini VP , Tan M , Jiang X , Green KY , Vinje J , Ding S , Greenberg HB . bioRxiv 2022 02 Rotaviruses (RVs) preferentially replicate in the small intestine, frequently cause severe diarrheal disease, and following enteric infection generally induce variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a missed opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued a replication-competent recombinant RRV harboring bicistronic gene segment 7 that encodes both the native RV NSP3 protein and a human norovirus (HuNoV) VP1 protein from the predominant genotype GII.4 (rRRV-HuNoV-VP1). The rRRV-HuNoV-VP1 expressed HuNoV VP1 in infected cells in vitro and importantly, elicited both systemic and local antibody responses to HuNoV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens while providing immunity to RV. 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. |
Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses.
Kawagishi T , Sánchez-Tacuba L , Feng N , Costantini VP , Tan M , Jiang X , Green KY , Vinjé J , Ding S , Greenberg HB . Proc Natl Acad Sci U S A 2023 120 (9) e2214421120 Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens. |
Malaria in pregnancy (MiP) studies assessing the clinical performance of highly sensitive rapid diagnostic tests (HS-RDT) for Plasmodium falciparum detection.
Ding XC , Incardona S , Serra-Casas E , Charnaud SC , Slater HC , Domingo GJ , Adams ER , Ter Kuile FO , Samuels AM , Kariuki S , Dittrich S . Malar J 2023 22 (1) 60 BACKGROUND: Rapid diagnostic tests (RDTs) are effective tools to diagnose and inform the treatment of malaria in adults and children. The recent development of a highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum has prompted questions over whether it could improve the diagnosis of malaria in pregnancy and pregnancy outcomes in malaria endemic areas. METHODS: This landscape review collates studies addressing the clinical performance of the HS-RDT. Thirteen studies were identified comparing the HS-RDT and conventional RDT (co-RDT) to molecular methods to detect malaria in pregnancy. Using data from five completed studies, the association of epidemiological and pregnancy-related factors on the sensitivity of HS-RDT, and comparisons with co-RDT were investigated. The studies were conducted in 4 countries over a range of transmission intensities in largely asymptomatic women. RESULTS: Sensitivity of both RDTs varied widely (HS-RDT range 19.6 to 85.7%, co-RDT range 22.8 to 82.8% compared to molecular testing) yet HS-RDT detected individuals with similar parasite densities across all the studies including different geographies and transmission areas [geometric mean parasitaemia around 100 parasites per µL (p/µL)]. HS-RDTs were capable of detecting low-density parasitaemias and in one study detected around 30% of infections with parasite densities of 0-2 p/µL compared to the co-RDT in the same study which detected around 15%. CONCLUSION: The HS-RDT has a slightly higher analytical sensitivity to detect malaria infections in pregnancy than co-RDT but this mostly translates to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity. The analysis presented here highlights the need for larger and more studies to evaluate incremental improvements in RDTs. The HS-RDT could be used in any situation where co-RDT are currently used for P. falciparum diagnosis, if storage conditions can be adhered to. |
COVID-19 Vaccine Uptake and Factors Affecting Hesitancy Among US Nurses, March-June 2021.
Rich-Edwards JW , Rocheleau CM , Ding M , Hankins JA , Katuska LM , Kumph X , Steege AL , Boiano JM , Lawson CC . Am J Public Health 2022 112 (11) 1620-1629 Objectives. To characterize COVID-19 vaccine uptake and hesitancy among US nurses. Methods. We surveyed nurses in 3 national cohorts during spring 2021. Participants who indicated that they did not plan to receive or were unsure whether they planned to receive the vaccine were considered vaccine hesitant. Results. Among 32426 female current and former nurses, 93% had been or planned to be vaccinated. After adjustment for age, race/ethnicity, and occupational variables, vaccine hesitancy was associated with lower education, living in the South, and working in a group care or home health setting. Those who experienced COVID-19 deaths and those reporting personal or household vulnerability to COVID-19 were less likely to be hesitant. Having contracted COVID-19 doubled the risk of vaccine hesitancy (95% confidence interval [CI]=1.85, 2.53). Reasons for hesitancy that were common among nurses who did not plan to receive the vaccine were religion/ethics, belief that the vaccine was ineffective, and lack of concern about COVID-19; those who were unsure often cited concerns regarding side effects or medical reasons or reported that they had had COVID-19. Conclusions. Vaccine hesitancy was unusual and stemmed from specific concerns. Public Health Implications. Targeted messaging and outreach might reduce vaccine hesitancy. (Am J Public Health. 2022;112(11):1620-1629. https://doi.org/10.2105/AJPH.2022.307050). |
The role of the VP4 attachment protein in rotavirus host range restriction in an in vivo suckling mouse model
Sánchez-Tacuba L , Kawagishi T , Feng N , Jiang B , Ding S , Greenberg HB . J Virol 2022 96 (15) e0055022 The basis for rotavirus (RV) host range restriction (HRR) is not fully understood but is likely multigenic. RV genes encoding VP3, VP4, NSP1, NSP2, NSP3, and NSP4 have been associated with HRR in various studies. With the exception of NSP1, little is known about the relative contribution of the other RV genes to HRR. VP4 has been linked to HRR because it functions as the RV cell attachment protein, but its actual role in HRR has not been fully assessed. We generated a collection of recombinant RVs (rRVs) in an isogenic murine-like RV genetic background, harboring either heterologous or homologous VP4 genes from simian, bovine, porcine, human, and murine RV strains, and characterized these rRVs in vitro and in vivo. We found that a murine-like rRV encoding a simian VP4 was shed, spread to uninoculated littermates, and induced diarrhea comparably to rRV harboring a murine VP4. However, rRVs carrying VP4s from both bovine and porcine RVs had reduced diarrhea, but no change in fecal shedding was observed. Both diarrhea and shedding were reduced when VP4 originated from a human RV strain. rRVs harboring VP4s from human or bovine RVs did not transmit to uninoculated littermates. We also generated two rRVs harboring reciprocal chimeric murine or bovine VP4. Both chimeras replicated and caused disease as efficiently as the parental strain with a fully murine VP4. These data suggest that the genetic origin of VP4 partially modulates HRR in the suckling mouse and that both the VP8* and VP5* domains independently contribute to pathogenesis and transmission. IMPORTANCE Human group A rotaviruses (RVs) remain the most important cause of severe acute gastroenteritis among infants and young children worldwide despite the introduction of several safe and effective live attenuated vaccines. The lack of knowledge regarding fundamental aspects of RV biology, such as the genetic basis of host range restriction (HRR), has made it difficult to predictively and efficiently design improved, next-generation live attenuated rotavirus vaccines. Here, we engineered a collection of VP4 monoreassortant RVs to systematically explore the role of VP4 in replication, pathogenicity, and spread, as measures of HRR, in a suckling mouse model. The genetic and mechanistic bases of HRR have substantial clinical relevance given that this restriction forms the basis of attenuation for several replication-competent human RV vaccines. In addition, a better understanding of RV pathogenesis and the determinants of RV spread is likely to enhance our ability to improve antiviral drug and therapy development. |
Cancer-associated venous thromboembolism: Incidence and features in a racially diverse population
Raskob GE , Wendelboe AM , Campbell J , Ford L , Ding K , Bratzler DW , McCumber M , Adamski A , Abe K , Beckman MG , Reyes NL , Richardson LC . J Thromb Haemost 2022 20 (10) 2366-2378 BACKGROUND: Data on the population-based incidence of cancer-associated venous thromboembolism (VTE) from racially diverse populations are limited. OBJECTIVE: To evaluate the incidence and burden of cancer-associated VTE, including demographic and racial subgroups in the general population of Oklahoma County-which closely mirrors the United States. DESIGN: Population-based prospective study. SETTING: We conducted surveillance of VTE at tertiary care facilities and outpatient clinics in Oklahoma County, Oklahoma from 2012-2014. Surveillance included reviewing all imaging reports used to diagnose VTE and identifying VTE events from hospital discharge data and death certificates. Cancer status was determined by linkage to the Oklahoma Central Cancer Registry. MEASUREMENTS: We used Poisson regression to calculate crude and age-adjusted incidences of cancer-associated VTE per 100,000 general population per year, with 95% confidence intervals (95% CI). RESULTS: The age-adjusted incidence (95% CI) of cancer-associated VTE among adults age 18 was 70.0 (65.1-75.3). The age-adjusted incidence rates (95% CI) were 85.9 (72.7-101.6) for non-Hispanic Black persons, 79.5 (13.2-86.5) for non-Hispanic White persons, 18.8 (8.9-39.4) for Native American persons, 15.6 (7.0-34.8) for Asian/Pacific Islander persons, and 15.2 (9.2-25.1) for Hispanic persons. Recurrent VTE up to 2years after the initial diagnosis occurred in 38 of 304 patients (12.5%) with active cancer and in 34 of 424 patients (8.0%) with a history of cancer >6 months previously. CONCLUSION: Age-adjusted incidence rates of cancer-associated VTE vary substantially by race and ethnicity. The relatively high incidences of first VTE and of recurrence warrant further assessment of strategies to prevent VTE among cancer patients. |
Per- and polyfluoroalkyl substances and incident hypertension in multi-racial/ethnic women: The Study of Women's Health Across the Nation
Ding N , Karvonen-Gutierrez CA , Mukherjee B , Calafat AM , Harlow SD , Park SK . Hypertension 2022 79 (8) 101161hypertensionaha12118809 BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous synthetic chemicals that may disrupt blood pressure controls; however, human evidence to support this hypothesis is scant. We examined the association between serum concentrations of PFAS and risks of developing hypertension. METHODS: This study included 1058 midlife women initially free of hypertension from the multiracial and multiethnic SWAN (Study of Women's Health Across the Nation) with annual follow-up visits between 1999 and 2017. Hypertension was defined as blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic or receiving antihypertensive treatment. Cox proportional hazards models were utilized to calculate hazard ratios and 95% CIs. Quantile g-computation was implemented to evaluate the joint effect of PFAS mixtures. RESULTS: During 11 722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Compared with the lowest tertile, women in the highest tertile of baseline serum concentrations had adjusted hazard ratios of 1.42 (95% CI, 1.19-1.68) for perfluorooctane sulfonate (P trend=0.01), 1.47 (95% CI, 1.24-1.75) for linear perfluorooctanoate (P trend=0.01), and 1.42 (95% CI, 1.19-1.70) for 2-(N-ethyl-perfluorooctane sulfonamido) acetate (P trend=0.01). No significant associations were observed for perfluorononanoate and perfluorohexane sulfonate. In the mixture analysis, women in the highest tertile of overall PFAS concentrations had a hazard ratio of 1.71 (95% CI, 1.15-2.54; P trend=0.008), compared with those in the lowest tertile. CONCLUSIONS: Several PFAS showed positive associations with incident hypertension. These findings suggest that PFAS might be an underappreciated contributing factor to women's cardiovascular disease risk. |
Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women's Health Across the Nation (SWAN)
Park SK , Wang X , Ding N , Karvonen-Gutierrez CA , Calafat AM , Herman WH , Mukherjee B , Harlow SD . Diabetologia 2022 65 (7) 1157-1168 AIMS/HYPOTHESIS: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). METHODS: We included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: After adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (p(trend) = 0.001), 1.58 (1.13, 2.21) for PFHxS (p(trend) = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (p(trend) = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (p(trend) = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (p(trend) = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS. CONCLUSIONS/INTERPRETATION: This study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk. |
PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis.
Li Q , Ye C , Zhao F , Li W , Zhu S , Lv Y , Park CG , Zhang Y , Jiang LY , Yang K , He Y , Cai H , Zhang S , Ding HH , Njiri OA , Tembo JM , Alkraiem AA , Li AY , Sun ZY , Li W , Yan MY , Kan B , Huo X , Klena JD , Skurnik M , Anisimov AP , Gao X , Han Y , Yang RF , Xiamu X , Wang Y , Chen H , Chai B , Sun Y , Yuan J , Chen T . Front Immunol 2022 13 791799 Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin. |
ROS generation is involved in titanium dioxide nanoparticle-induced AP-1 activation through p38 MAPK and ERK pathways in JB6 cells
Kong L , Barber T , Aldinger J , Bowman L , Leonard S , Zhao J , Ding M . Environ Toxicol 2021 37 (2) 237-244 Titanium dioxide (TiO(2) ) is generally regarded as a nontoxic and nongenotoxic white mineral, which is mainly applied in the manufacture of paper, paint, plastic, sunscreen lotion and other products. Recently, TiO(2) nanoparticles (TiO(2) NPs) have been demonstrated to cause chronic inflammation and lung tumor formation in rats, which may be associated with the particle size of TiO(2) . Considering the important role of activator protein-1 (AP-1) in regulating multiple genes involved in the cell proliferation and inflammation and the induction of neoplastic transformation, we aimed to evaluate the potency of TiO(2) NPs (≤ 20 nm) on the activation of AP-1 signaling pathway and the generation of reactive oxygen species (ROS) in a mouse epidermal cell line, JB6 cells. MTT, electron spin resonance (ESR), AP-1 luciferase activity assay in vitro and in vivo, and Western blotting assay were used to clarify this problem. Our results indicated that TiO(2) NPs dose-dependently caused the hydroxyl radical (·OH) generation and sequentially increased the AP-1 activity in JB6 cells. Using AP-1-luciferase reporter transgenic mice models, an obvious increased AP-1 activity was detected in dermal tissue after exposure to TiO(2) NPs for 24 h. Interestingly, TiO(2) NPs increased the AP-1 activity via stimulating the expression of mitogen-activated protein kinases (MAPKs) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinases (JNKs). Of note, the AP-1 activation induced by TiO(2) NPs could be blocked by specific inhibitors (SB203580, PD98059, and SP 600125, respectively) that inhibit ERKs and p38 kinase but not JNKs. These findings indicate that ROS generation is involved in TiO(2) NPs-induced AP-1 activation mediated by MAPKs signal pathway. |
Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis
Muchtar E , Koehler AB , Johnson MJ , Rabe KG , Ding W , Call TG , Leis JF , Kenderian SS , Hayman SR , Wang Y , Hampel PJ , Holets MA , Darby HC , Slager SL , Kay NE , Miao C , Canniff J , Whitaker JA , Levin MJ , Schmid DS , Kennedy RB , Weinberg A , Parikh SA . Am J Hematol 2021 97 (1) 90-98 Monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B cell disorders associated with increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by two months. Responses assessed at 3-months and 12-months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color IFN-γ and IL-2 FLUOROSPOT assays were compared to historic controls matched by age and sex. Sixty-two patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, P=0.03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs 36%, respectively, P=0.23). The CD4+ T cell response to vaccination was significantly lower in study participants compared to controls (54% vs 96%, P<0.001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs 73%, P=0.008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n=47), 24% had antibody titers below response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed. This article is protected by copyright. All rights reserved. |
American Frontline Healthcare Personnel's Access to and Use of Personal Protective Equipment Early in the COVID-19 Pandemic.
Rich-Edwards JW , Ding M , Rocheleau CM , Boiano JM , Kang JH , Becene I , Nguyen LH , Chan AT , Hart JE , Chavarro JE , Lawson CC . J Occup Environ Med 2021 63 (11) 913-920 OBJECTIVES: To quantify adequacy of personal protective equipment (PPE) for U.S. healthcare personnel (HCP) at the outset of the COVID-19 pandemic and its association with infection risk. METHODS: March-May 2020 survey of the national Nurses' Health Studies and the Growing Up Today study regarding self-reported PPE access, use and reuse. COVID-19 endpoints included SARS-CoV-2 tests and COVID-19 status predicted from symptoms. RESULTS: Nearly 22% of 22,232 frontline HCP interacting with COVID-19 patients reported sometimes or always lacking PPE. Fifty percent of HCP reported not needing respirators, including 13% of those working in COVID-19 units. Lack of PPE was cross-sectionally associated with two-fold or greater odds of COVID-19 among those who interacted with infected patients. CONCLUSION: These data show the need to improve the U.S. infection prevention culture of safety when confronting a novel pathogen. |
Per- and Polyfluoroalkyl Substances (PFAS) and Hormone Levels during the Menopausal Transition
Harlow SD , Hood MM , Ding N , Mukherjee B , Calafat AM , Randolph JF , Gold EB , Park SK . J Clin Endocrinol Metab 2021 106 (11) e4427-e4437 CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women. OBJECTIVE: To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016. DESIGN: Prospective cohort. SETTING: General community. PARTICIPANTS: 1,371 midlife women aged 45-56 years at baseline in the Study of Women's Health Across the Nation (SWAN). MAIN OUTCOME MEASURE(S): FSH, estradiol, testosterone, SHBG. RESULTS: In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity and body mass index, FSH was positively associated with linear perfluorooctanoate (n-PFOA) (3.12% (95% CI: 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate (n-PFOS) (2.88% (0.21%, 5.63%)), branched perfluorooctane sulfonate (Sm-PFOS) (2.25% (0.02%, 4.54%)), total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) (1.70% (0.01%, 3.42%)). Estradiol was inversely associated with perfluorononanoate (PFNA) (-2.47% (-4.82%, -0.05%)) and n-PFOA (-2.43% (-4.97%, 0.18%)). Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps-trend≤0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone. CONCLUSIONS: This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging. |
Associations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS mixtures with adipokines in midlife women
Ding N , Karvonen-Gutierrez CA , Herman WH , Calafat AM , Mukherjee B , Park SK . Int J Hyg Environ Health 2021 235 113777 BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure have been associated with obesity and related comorbidities, possibly through disrupting signaling pathways of adipokines. Both leptin and adiponectin can modulate metabolic processes. However, the effects of PFAS on adipokines are not well understood. OBJECTIVE: We determined if serum PFAS concentrations were associated with adipokine profiles in midlife women. METHODS: We examined 1245 women aged 45-56 years from the Study of Women's Health Across the Nation. Concentrations of 11 PFAS were quantified in baseline serum samples collected in 1999-2000. Linear and branched perfluorooctane sulfonic acid isomers (n-PFOS and Sm-PFOS) and their sum (PFOS), linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA) with detection frequencies >60% were included in the analysis. Adipokines including leptin, soluble leptin receptor (sOB-R), free leptin index (FLI, the ratio of leptin to sOB-R), total and high molecular weight (HMW) adiponectin were assessed in 2002-2003. We utilized multivariable linear regressions and Bayesian kernel machine regression (BKMR) to assess individual and overall joint effects of PFAS on adipokines with adjustment for age, race/ethnicity, study site, education, smoking status, physical activity, menopausal status, and waist circumference. RESULTS: A doubling of PFAS concentrations was associated with 7.8% (95% CI: 2.5%, 13.4%) higher FLI for PFOS, 9.4% (95% CI: 3.7%, 15.3%) for n-PFOA, 5.5% (95% CI: 2.2%, 9.0%) for EtFOSAA and 7.4% (95% CI: 2.8%, 12.2%) for MeFOSAA. Similar associations were found for leptin. Only EtFOSAA was associated with lower sOB-R concentrations (-1.4%, 95% CI: -2.7%, -0.1%). Results remained in women with overweight or obesity but not those with normal weight or underweight. No statistically significant associations were observed with total or HMW adiponectin, except for PFNA with total and HMW adiponectin observed in women with normal weight or underweight. In BKMR analysis, women with PFAS concentrations at the median and the 90th percentile had 30.9% (95% CI: 15.6%, 48.3%) and 52.1% (95% CI: 27.9%, 81.0%) higher FLI, respectively, compared with those with concentrations fixed at the 10th percentile. CONCLUSION: Some PFAS may alter circulating levels of leptin. Understanding associations between PFAS and adipokines may help elucidate whether PFAS can influence obesity and metabolic disease. |
Closing the Brief Case: Disseminated Microsporidiosis with Intestinal Cryptosporidium Coinfection in a Patient with Kaposi's Sarcoma and Castleman Disease Presenting with Acute Kidney Injury
Agarwal AN , Shieh WJ , Goldsmith CS , Qvarnstrom Y , Ding Y , Dallas SD , Mais DD . J Clin Microbiol 2021 59 (6) Microsporidia are unicellular obligate parasitic fungi which produce heat-resistant spores. | The spores are infective forms containing a coiled polar tubule, which is extruded in the host cell to inject sporoplasm. | Transmission electron microscopy is the gold standard test for identification of microsporidia. Other tests for identification include Gram stain, Chromotrope 2R, quick-hot Gram chromotrope technique, trichrome blue, acid-fast stain, Warthin-Starry stain, modified trichrome stains, calcofluor white, immunohistochemistry, and PCR. | Encephalitozoon intestinalis commonly infects the gastrointestinal tract. However, it can also infect the kidneys and lungs. Microsporidiosis should be considered as a cause of renal failure in an immunocompromised patient. |
Occupational exposure to high-level disinfectants and risk of miscarriage among nurses
Ding M , Lawson C , Johnson C , Rich-Edwards J , Gaskins AJ , Boiano J , Henn S , Rocheleau C , Chavarro JE . Occup Environ Med 2021 78 (10) 731-737 OBJECTIVES: To examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses. METHODS: Our study included women who enrolled in the Nurses' Health Study 3 (2010-2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs. RESULTS: Our study included 2579 nurses with a median of 5.6 years of follow-up (range: 1-9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93). CONCLUSIONS: We observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously. |
Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the Study of Women's Health Across the Nation 1999-2018
Ding N , Karvonen-Gutierrez CA , Herman WH , Calafat AM , Mukherjee B , Park SK . Int J Obes (Lond) 2021 45 (9) 1937-1948 BACKGROUND/OBJECTIVES: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. SUBJECTS/METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS: After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. CONCLUSIONS: Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk. |
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Wu BC , Olivia NA , Tembo JM , He YX , Zhang YM , Xue Y , Ye CL , Lv Y , Li WJ , Jiang LY , Huo XX , Sun ZY , Chen ZJ , Qin JC , Li AY , Park CG , Klena JD , Ding HH , Chen T . J Med Microbiol 2021 70 (3) Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors. |
Fatal Case of Chronic Jamestown Canyon Virus Encephalitis Diagnosed by Metagenomic Sequencing in Patient Receiving Rituximab.
Solomon IH , Ganesh VS , Yu G , Deng XD , Wilson MR , Miller S , Milligan TA , Mukerji SS , Mathewson A , Linxweiler J , Morse D , Ritter JM , Staples JE , Hughes H , Gould CV , Sabeti PC , Chiu CY , Piantadosi A . Emerg Infect Dis 2021 27 (1) 238-42 A 56-year-old man receiving rituximab who had months of neurologic symptoms was found to have Jamestown Canyon virus in cerebrospinal fluid by clinical metagenomic sequencing. The patient died, and postmortem examination revealed extensive neuropathologic abnormalities. Deep sequencing enabled detailed characterization of viral genomes from the cerebrospinal fluid, cerebellum, and cerebral cortex. |
Incidence of venous thromboembolism in a racially diverse population of Oklahoma County, Oklahoma
Wendelboe AM , Campbell J , Ding K , Bratzler DW , Beckman MG , Reyes NL , Raskob GE . Thromb Haemost 2021 121 (6) 816-825 BACKGROUND: Contemporary incidence data for venous thromboembolism (VTE) from racially diverse populations are limited. The racial distribution of Oklahoma County closely mirrors that of the United States. OBJECTIVE: To evaluate VTE incidence and mortality, including demographic and racial subgroups. DESIGN: Population-based prospective study. SETTING: We conducted VTE surveillance at all relevant tertiary care facilities and outpatient clinics in Oklahoma County, Oklahoma during 2012 to 2014, using both active and passive methods. Active surveillance involved reviewing all imaging reports used to diagnose VTE. Passive surveillance entailed identifying VTE events from hospital discharge data and death certificate records. MEASUREMENTS: We used Poisson regression to calculate crude, age-stratified, and age-adjusted incidence and mortality rates per 1,000 population per year and 95% confidence intervals (CIs). RESULTS: The incidence rate of all VTE was 3.02 (2.92-3.12) for those age ≥18 years and 0.05 (0.04-0.08) for those <18 years. The age-adjusted incidence rates of all VTE, deep vein thrombosis, and pulmonary embolism were 2.47 (95% CI: 2.39-2.55), 1.47 (1.41-1.54), and 0.99 (0.93-1.04), respectively. The age-adjusted VTE incidence and the 30-day mortality rates, respectively, were 0.63 and 0.121 for Asians/Pacific Islanders, 3.25 and 0.355 for blacks, 0.67 and 0.111 for Hispanics, 1.25 and 0.195 for Native Americans, and 2.71 and 0.396 for whites. CONCLUSION: The age-adjusted VTE incidence and mortality rates vary substantially by race. The incidence of three per 1,000 adults per year indicates an important disease burden, and is informative of the burden in the U.S. |
An optimized reverse genetics system suitable for efficient recovery of simian, human and murine-like rotaviruses.
Sanchez-Tacuba L , Feng N , Meade NJ , Mellits KH , Jais PH , Yasukawa LL , Resch TK , Jiang B , Lopez S , Ding S , Greenberg HB . J Virol 2020 94 (18) An entirely plasmid-based reverse genetics (RG) system was recently developed for rotavirus (RV), opening new avenues for in-depth molecular dissection of RV biology, immunology, and pathogenesis. Several improvements to further optimize the RG efficiency have now been described. However, only a small number of individual RV strains have been recovered to date. None of the current methods have supported the recovery of murine RV, impeding the study of RV replication and pathogenesis in an in vivo suckling mouse model. Here, we describe useful modifications to the RG system that significantly improve rescue efficiency of multiple RV strains. In addition to the 11 RVA segment-specific (+)ssRNAs, a chimeric plasmid was transfected, from which the capping enzyme NP868R of African swine fever virus (ASFV) and the T7 RNA polymerase were expressed. Secondly, a genetically modified MA104 cell line was used in which several compounds of the innate immune were degraded. Using this RG system, we successfully recovered the simian RV RRV strain, the human RV CDC-9 strain, a reassortant between murine RV D6/2 and simian RV SA11 strains, and several reassortants and reporter RVs. All these recombinant RVs were rescued at a high efficiency (≥80% success rate) and could not be reliably rescued using several recently published RG strategies (<20%). This improved system represents an important tool and great potential for the rescue of other hard-to-recover RV strains such as low replicating attenuated vaccine candidates or low cell culture passage clinical isolates from humans or animals.IMPORTANCE Group A rotavirus (RV) remains as the single most important cause of severe acute gastroenteritis among infants and young children worldwide. An entirely plasmid-based reverse genetics (RG) system was recently developed opening new ways for in-depth molecular study of RV. Despite several improvements to further optimize the RG efficiency, it has been reported that current strategies do not enable the rescue of all cultivatable RV strains. Here, we described helpful modification to the current strategies and established a tractable RG system for the rescue of the simian RRV strain, the human CDC-9 strain and a murine-like RV strain, which is suitable for both in vitro and in vivo studies. This improved RV reverse genetics system will facilitate study of RV biology in both in vitro and in vivo systems that will facilitate the improved design of RV vaccines, better antiviral therapies and expression vectors. |
Gender disparity in academic rank and productivity among public health physician faculty in North America
Lee D , Jalal S , Nasrullah M , Ding J , Sanelli P , Khosa F . Cureus 2020 12 (6) e8553 Background The issue of gender disparity is particularly important in the domain of public health where the tone of its leadership is pivotal in bringing about impactful change to research, policies, and the wellbeing of our various populations. Our aim is to explore the gender disparity of author metrics and academic rankings of public health physician faculty through a cross-sectional study. Methods Data collection for this retrospective cross-sectional study took place during June and July of 2017. Public health and preventive medicine residency training programs in the United States and Canada were to compiled and all faculty members that met the inclusion criteria were recorded (n = 973). Variables of interest include gender, h-index, years of active research, and academic appointments. SCOPUS database (Elsevier, Amsterdam, the Netherlands) was used to generate author metrics, and all statistical tests were performed using Statistical Package for the Social Sciences (SPSS) software version 20 (IBM Corp., Armonk, NY). Results Overall, 31.14% (n = 303) of faculty members we studied were from Canada, and 68.86% (n = 670) were from the United States. In both countries, males made up the majority of all faculty members. Female faculty comprised most of the early career positions, and their proportions tapered off with higher academic rank, whereas male faculty trended in the opposite direction. Males generally were higher in all academic measures across all appointments. Conclusions Gender disparity exists within the North American public health and preventive medicine discipline. There are underlying factors preventing women from moving beyond early career positions or engaging in academic research. |
Association of a province-wide intervention with salt intake and hypertension in Shandong Province, China, 2011-2016
Xu A , Ma J , Guo X , Wang L , Wu J , Zhang J , Bai Y , Xu J , Lu Z , Xu Z , Zhang X , Ding G , Hong Y , Du F , Wu Y , Yan L , Tang J , Cai X , Dong J , Xu C , Ren J , Chen X , Gao C , Zhang B , Yang Q , Moolenaar R , Cai Y , Jackson SL , Xie G , Yu S , Cui J , Wang Z , Zhao L , Ju L , Shen D , Yun S , Liang X , Bi Z , Wang Y . JAMA Intern Med 2020 180 (6) 877-86 IMPORTANCE: High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. OBJECTIVE: To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. INTERVENTIONS: Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. MAIN OUTCOMES AND MEASURES: The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. RESULTS: Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. CONCLUSIONS AND RELEVANCE: The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide. |
Associations of perfluoroalkyl substances with incident natural menopause: the Study of Women's Health Across the Nation
Ding N , Harlow SD , Randolph JF , Calafat AM , Mukherjee B , Batterman S , Gold EB , Park SK . J Clin Endocrinol Metab 2020 105 (9) e3169-82 CONTEXT: Previous epidemiologic studies of per- and polyfluoroalkyl substances (PFAS) and menopausal timing conducted in cross-sectional settings were limited by reverse causation because PFAS serum concentrations increase after menopause. OBJECTIVES: To investigate associations between perfluoroalkyl substances and incident natural menopause. DESIGN AND SETTING: A prospective cohort of midlife women, the Study of Women's Health Across the Nation, 1999-2017. PARTICIPANTS: 1120 multi-racial/ethnic premenopausal women aged 45-56 years. METHODS: Serum concentrations of perfluoroalkyls were quantified by high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Natural menopause was defined as the bleeding episode prior to at least 12 months of amenorrhea not due to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Participants contributed 5466 person-years of follow-up, and 578 had incident natural menopause. Compared to the lowest tertile, women at the highest tertile of baseline serum concentrations had adjusted HR for natural menopause of 1.26 (95%CI: 1.02-1.57) for n-perfluorooctane sulfonic acid (n-PFOS) (Ptrend=0.03), 1.27 (95%CI: 1.01-1.59) for branched-PFOS (Ptrend=0.03), and 1.31 (95%CI: 1.04-1.65) for n-perfluorooctanoic acid (Ptrend=0.01). Women were classified into four clusters based on their overall PFAS concentrations as mixtures: low, low-medium, medium-high, and high. Compared to the low cluster, the high cluster had a HR of 1.63 (95% CI: 1.08-2.45), which is equivalent to 2.0 years earlier median time to natural menopause. CONCLUSION: This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life. |
Joint toxicity of a multi-heavy metal mixture and chemoprevention in Sprague Dawley rats
Wang Y , Tang Y , Li Z , Hua Q , Wang L , Song X , Zou B , Ding M , Zhao J , Tang C . Int J Environ Res Public Health 2020 17 (4) To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg*bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg*bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg*bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed. |
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