Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-11 (of 11 Records) |
Query Trace: Kenny K[original query] |
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Network analysis of the chronic Hepatitis C virome defines HVR1 evolutionary phenotypes in the context of humoral immune responses.
Palmer BA , Schmidt-Martin D , Dimitrova Z , Skums P , Crosbie O , Kenny-Walsh E , Fanning LJ . J Virol 2015 90 (7) 3318-29 Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. IMPORTANCE: HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness. |
The eligibility and reach of the national breast and cervical cancer early detection program after implementation of the affordable care act
Tangka F , Kenny K , Miller J , Howard DH . Cancer Causes Control 2020 31 (5) 473-489 INTRODUCTION: The uninsured rate declined following passage of the Affordable Care Act in 2010. It is unclear how this decrease affected the size of the population eligible for existing safety net programs. We evaluated trends in the number of women eligible for breast and cervical cancer screening and diagnostic services under the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and the reach of the program. METHODS: Using the Census Bureau's Small Area Health Insurance Estimates data, we calculated the number of women who met the NBCCEDP eligibility criteria based on age, income, and insurance status. We used these data in conjunction with program to estimate the proportion of eligible women served by the NBCCEDP. RESULTS: The number of women eligible for breast cancer screening and diagnostic services under the program declined from 5.4 (90% CI 5.2-5.6) to 2.8 (90% CI 2.6-3.0) million from 2011 to 2017. The number of women eligible for cervical cancer screening and diagnostic services declined from 10.3 (90% CI 10.0-10.6) to 5.3 (90% CI 5.1-5.6) million. The share of eligible women served by the program was 15.0% (90% CI 14.8-15.1%) for breast services in 2016-2017 and 6.8% (90% CI 6.7-6.8%) for cervical services in 2015-2017. CONCLUSION: Insurance coverage expansions may have contributed to a decrease in the number of program-eligible women. There are many more women eligible for the program than are served. |
Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of mRNAs targeted for AGO2-mediated silencing.
Nawaz A , Kenny PJ , Shilikbay T , Reed M , Stuchlik O , Pohl J , Ceman S . J Biol Chem 2023 299 (4) 104577 MOV10 is an RNA helicase that is required for organismal development and is highly expressed in postnatal brain. MOV10 was identified as an AGO2 associated protein that is also necessary for AGO2-mediated silencing. AGO2 is the primary effector of the miRNA pathway. MOV10 has been shown to be ubiquitinated, leading to its degradation and release from bound mRNAs but no other post-translational modifications with functional implications have been described. Using mass spectrometry, we show that MOV10 is phosphorylated in cells at the C-terminus, specifically at serine 970 (S970). Substitution of S970 to phospho-mimic aspartic acid (S970D) blocked unfolding of an RNA G-quadruplex, similar to when the helicase domain was mutated (K531A). In contrast, the alanine substitution (S970A) of MOV10 unfolded the model RNA G-quadruplex. To examine its role in cells, our RNA-seq analysis showed that the expression of S970D causes decreased expression of MOV10 enhanced Cross-Linking Immunoprecipitation (eCLIP) targets compared to WT. Introduction of S970A had an intermediate effect, suggesting that S970 was protective of mRNAs. In whole cell extracts, MOV10 and its substitutions bound AGO2 comparably; however, knockdown of AGO2 abrogated the S970D-induced mRNA degradation. Thus, MOV10 activity protects mRNA from AGO2; phosphorylation of S970 restricts this activity resulting in AGO2-mediated mRNA degradation. S970 is positioned C-terminal to the defined MOV10-AGO2 interaction site and is proximal to a disordered region that likely modulates AGO2 interaction with target mRNAs upon phosphorylation. In summary, we provide evidence for a model whereby MOV10 phosphorylation facilitates AGO2 association with the 3'UTR of translating mRNAs that leads to their degradation. |
Screening for Viral Nucleic Acids in the Cerebrospinal Fluid of Dogs With Central Nervous System Inflammation.
Barber RM , Li Q , Levine JM , Ruone SJ , Levine GJ , Kenny P , Tong S , Schatzberg SJ . Front Vet Sci 2022 9 850510 Central nervous system (CNS) inflammation is a common cause of neurological dysfunction in dogs. Most dogs with CNS inflammation are diagnosed with presumptive autoimmune disease. A smaller number are diagnosed with an infectious etiology. Additionally, at necropsy, a subset of dogs with CNS inflammation do not fit previously described patterns of autoimmune disease and an infectious cause is not readily identifiable. Because viral infection is a common cause of meningoencephalitis in people, we hypothesize that a subset of dogs presented with CNS inflammation have an occult viral infection either as a direct cause of CNS inflammation or a trigger for autoimmunity. The goal of this research was to screen cerebrospinal fluid from a large number dogs with CNS inflammation for occult viral infection. One hundred seventy-two dogs with neurological dysfunction and cerebrospinal fluid (CSF) pleocytosis were identified. Of these, 42 had meningoencephalitis of unknown origin, six had steroid-responsive meningitis-arteritis, one had eosinophilic meningoencephalitis, five had documented infection, 21 had and undetermined diagnosis, and 97 had a diagnosis not consistent with primary inflammatory disease of the CNS (e.g., neoplasia). CSF samples were subsequently screened with broadly reactive PCR for eight viral groups: adenovirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, and parechovirus. No viral nucleic acids were detected from 168 cases screened for eight viral groups, which does not support occult viral infection as a cause of CNS inflammation in dogs. La Crosse virus (LACV) nucleic acids were detected from four cases in Georgia. Subclinical infection was supported in two of these cases but LACV could not be ruled-out as a cause of infection in the other two cases, suggesting further research is warranted to determine if LACV is an occult cause of CNS inflammation in dogs. |
Accuracy of Case-Based Seroprevalence of SARS-CoV-2 Antibodies in Maricopa County, Arizona.
Jehn M , Pandit U , Sabin S , Tompkins C , White J , Kaleta E , Dale AP , Ross HM , MacMcCullough J , Pepin S , Kenny K , Sanborn H , Heywood N , Schnall AH , Lant T , Sunenshine R . Am J Public Health 2022 112 (1) 38-42 We conducted a community seroprevalence survey in Arizona, from September 12 to October 1, 2020, to determine the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the seroprevalence estimate to predict SARS-CoV-2 infections in the jurisdiction by applying the adjusted seroprevalence to the county's population. The estimated community seroprevalence of SARS-CoV-2 infections was 4.3 times greater (95% confidence interval=2.2, 7.5) than the number of reported cases. Field surveys with representative sampling provide data that may help fill in gaps in traditional public health reporting. (Am J Public Health. 2022;112(1):38-42. https://doi.org/10.2105/AJPH.2021.306568). |
Observed Face Mask Use at Six Universities - United States, September-November 2020.
Barrios LC , Riggs MA , Green RF , Czarnik M , Nett RJ , Staples JE , Welton MD , Muilenburg JL , Zullig KJ , Gibson-Young L , Perkins AV , Prins C , Lauzardo M , Shapiro J , Asimellis G , Kilgore-Bowling G , Ortiz-Jurado K , Gutilla MJ . MMWR Morb Mortal Wkly Rep 2021 70 (6) 208-211 Approximately 41% of adults aged 18-24 years in the United States are enrolled in a college or university (1). Wearing a face mask can reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (2), and many colleges and universities mandate mask use in public locations and outdoors when within six feet of others. Studies based on self-report have described mask use ranging from 69.1% to 86.1% among adults aged 18-29 years (3); however, more objective measures are needed. Direct observation by trained observers is the accepted standard for monitoring behaviors such as hand hygiene (4). In this investigation, direct observation was used to estimate the proportion of persons wearing masks and the proportion of persons wearing masks correctly (i.e., covering the nose and mouth and secured under the chin*) on campus and at nearby off-campus locations at six rural and suburban universities with mask mandates in the southern and western United States. Trained student observers recorded mask use for up to 8 weeks from fixed sites on campus and nearby. Among 17,200 observed persons, 85.5% wore masks, with 89.7% of those persons wearing the mask correctly (overall correct mask use: 76.7%). Among persons observed indoors, 91.7% wore masks correctly. The proportion correctly wearing masks indoors varied by mask type, from 96.8% for N95-type masks and 92.2% for cloth masks to 78.9% for bandanas, scarves, and similar face coverings. Observed indoor mask use was high at these six universities with mask mandates. Colleges and universities can use direct observation findings to tailor training and messaging toward increasing correct mask use. |
Heat stress assessment during intermittent work under different environmental conditions and clothing combinations of effective wet bulb globe temperature (WBGT)
Seo Y , Powell J , Strauch A , Roberge R , Kenny GP , Kim JH . J Occup Environ Hyg 2019 16 (7) 1-10 This study examined whether different combinations of ambient temperature and relative humidity for the effective wet bulb globe temperature, in conjunction with two different levels of clothing adjustment factors, elicit a similar level of heat strain consistent with the current threshold limit value guidelines. Twelve healthy, physically active men performed four 15-min sessions of cycling at a fixed rate of metabolic heat production of 350 watts. Each trial was separated by a 15-min recovery period under four conditions: (1) Cotton coveralls + dry condition (WD: 45.5 degrees C dry-bulb, 15% relative humidity); (2) Cotton coveralls + humid condition (WH: 31 degrees C dry-bulb, 84% relative humidity); (3) Protective clothing + dry condition (PD: 30 degrees C dry-bulb, 15% relative humidity); and (4) Protective clothing + humid condition (PH: 20 degrees C dry-bulb, 80% relative humidity). Gloves (mining or chemical) and headgear (helmet or powered air-purifying respirator) were removed during recovery with hydration ad libitum. Rectal temperature (Tre), skin temperature (Tsk), physiological heat strain (PSI), perceptual heat strain (PeSI), and body heat content were calculated. At the end of the 2-hr trials, Tre remained below 38 degrees C and the magnitude of Tre elevation was not greater than 1 degrees C in all conditions (WD: 0.9, WH: 0.8, WH: 0.7, and PD: 0.6 degrees C). However, Tsk was significantly increased by approximately 2.1 +/- 0.8 degrees C across all conditions (all p </= 0.001). The increase in Tsk was the highest in WD followed by PD, WH, and PH conditions (all p </= 0.001). Although PSI and PeSI did not indicate severe heat strain during the 2-hr intermittent work period, PSI and PeSI were significantly increased over time (p </= 0.001). This study showed that core temperature and heat strain indices (PSI and PeSI) increased similarly across the four conditions. However, given that core temperature increased continuously during the work session, it is likely that the American Conference of Governmental Industrial Hygienist's TLV((R)) upper limit core temperature of 38.0 degrees C may be surpassed during extended work periods under all conditions. |
Postexercise whole-body sweating increases during muscle metaboreceptor activation in young men
Friesen BJ , Poirier MP , Lamarche DT , D'Souza AW , Kim JH , Notley SR , Kenny GP . Appl Physiol Nutr Metab 2018 43 (4) 423-426 We assessed the effect of metaboreceptor activation on whole-body evaporative heat loss (WB-EHL) in twelve men (24+/-4 years) in the early-to-late-stages of a 60-min exercise recovery in the heat. Metaboreceptor activation induced by 1-min isometric-handgrip (IHG) exercise followed by 5-min forearm ischemia to trap metabolites increased WB-EHL by 25-31% and 26-34% during the ischemic period relative to IHG-Only and Control (natural recovery only) respectively throughout recovery. We show that metaboreceptor activation enhances WB-EHL in recovery. |
Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys
Warren TK , Jordan R , Lo MK , Ray AS , Mackman RL , Soloveva V , Siegel D , Perron M , Bannister R , Hui HC , Larson N , Strickley R , Wells J , Stuthman KS , Van Tongeren SA , Garza NL , Donnelly G , Shurtleff AC , Retterer CJ , Gharaibeh D , Zamani R , Kenny T , Eaton BP , Grimes E , Welch LS , Gomba L , Wilhelmsen CL , Nichols DK , Nuss JE , Nagle ER , Kugelman JR , Palacios G , Doerffler E , Neville S , Carra E , Clarke MO , Zhang L , Lew W , Ross B , Wang Q , Chun K , Wolfe L , Babusis D , Park Y , Stray KM , Trancheva I , Feng JY , Barauskas O , Xu Y , Wong P , Braun MR , Flint M , McMullan LK , Chen SS , Fearns R , Swaminathan S , Mayers DL , Spiropoulou CF , Lee WA , Nichol ST , Cihlar T , Bavari S . Nature 2016 531 (7594) 381-5 The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg-1 GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing. |
An evaluation of sharp cut cyclones for sampling diesel particulate matter aerosol in the presence of respirable dust
Cauda E , Sheehan M , Gussman R , Kenny L , Volkwein J . Ann Occup Hyg 2014 58 (8) 995-1005 Two prototype cyclones were the subjects of a comparative research campaign with a diesel particulate matter sampler (DPMS) that consists of a respirable cyclone combined with a downstream impactor. The DPMS is currently used in mining environments to separate dust from the diesel particulate matter and to avoid interferences in the analysis of integrated samples and direct-reading monitoring in occupational environments. The sampling characteristics of all three devices were compared using ammonium fluorescein, diesel, and coal dust aerosols. With solid spherical test aerosols at low particle loadings, the aerodynamic size-selection characteristics of all three devices were found to be similar, with 50% penetration efficiencies (d 50) close to the design value of 0.8 mum, as required by the US Mine Safety and Health Administration for monitoring occupational exposure to diesel particulate matter in US mining operations. The prototype cyclones were shown to have 'sharp cut' size-selection characteristics that equaled or exceeded the sharpness of the DPMS. The penetration of diesel aerosols was optimal for all three samplers, while the results of the tests with coal dust induced the exclusion of one of the prototypes from subsequent testing. The sampling characteristics of the remaining prototype sharp cut cyclone (SCC) and the DPMS were tested with different loading of coal dust. While the characteristics of the SCC remained constant, the deposited respirable coal dust particles altered the size-selection performance of the currently used sampler. This study demonstrates that the SCC performed better overall than the DPMS. |
Standardized methods and quality control limits for agar and broth microdilution susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum
Waites KB , Duffy LB , Bebear CM , Matlow A , Talkington DF , Kenny GE , Totten PA , Bade DJ , Zheng X , Davidson MK , Shortridge VD , Watts JL , Brown SD . J Clin Microbiol 2012 50 (11) 3542-7 An international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum using broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3- to 4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans. |
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