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Search Results for all work with filters:

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Work 1-10 of 505

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Article

Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma

by Frederico O. Gleber-Netto; Mei Zhao; Sanchit Trivedi; Jiping Wang; Samar Jasser; Christina McDowell; Humam Kadara; Jiexin Zhang; Jing Wang; William N. William Jr.; J. Jack Lee; Minhly Nguyen; Sara I. Pai; Heather M. Walline; Dong Shin; Robert L. Ferris; Thomas E. Carey; Jeffrey N. Myers; Curtis R. Pickering

2018

Subjects
  • Health Sciences, Oncology
  • Health Sciences, Immunology
  • Biology, Biostatistics
  • File Download
  • View Abstract

Abstract:Close

BACKGROUND: Human immunodeficiency virus–infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non–HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non–HIV-related HNSCC. METHODS: The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non–HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. RESULTS: HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non–HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. CONCLUSIONS: HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94.

Article

Extensively Drug-Resistant Pseudomonas aeruginosa Isolates Containing bla(VIM-2) and Elements of Salmonella Genomic Island 2: a New Genetic Resistance Determinant in Northeast Ohio

by Federico Perez; Andrea M. Hujer; Steven H. Marshall; Amy J. Ray; Philip Rather; Nuntra Suwantarat; Donald Dumford; Patrick O'Shea; T. Nicholas J. Domitrovic; Robert A. Salata; Kalyan D. Chavda; Liang Chen; Barry N. Kreiswirth; Alejandro J. Vila; Susanne Haussler; Michael R. Jacobs; Robert A. Bonomo

2014

Subjects
  • Health Sciences, Pharmacology
  • Biology, Microbiology
  • Health Sciences, Immunology
  • File Download
  • View Abstract

Abstract:Close

Carbapenems are a mainstay of treatment for infections caused by Pseudomonas aeruginosa. Carbapenem resistance mediated by metallo-β-lactamases (MBLs) remains uncommon in the United States, despite the worldwide emergence of this group of enzymes. Between March 2012 and May 2013, we detected MBL-producing P. aeruginosa in a university-affiliated health care system in northeast Ohio. We examined the clinical characteristics and outcomes of patients, defined the resistance determinants and structure of the genetic element harboring the blaMBL gene through genome sequencing, and typed MBL-producing P. aeruginosa isolates using pulsed-field gel electrophoresis (PFGE), repetitive sequence-based PCR (rep-PCR), and multilocus sequence typing (MLST). Seven patients were affected that were hospitalized at three community hospitals, a long-term-care facility, and a tertiary care center; one of the patients died as a result of infection. Isolates belonged to sequence type 233 (ST233) and were extensively drug resistant (XDR), including resistance to all fluoroquinolones, aminoglycosides, and β-lactams; two isolates were nonsusceptible to colistin. The blaMBL gene was identified as blaVIM-2 contained within a class 1 integron (In559), similar to the cassette array previously detected in isolates from Norway, Russia, Taiwan, and Chicago, IL. Genomic sequencing and assembly revealed that In559 was part of a novel 35-kb region that also included a Tn501-like transposon and Salmonella genomic island 2 (SGI2)-homologous sequences. This analysis of XDR strains producing VIM-2 from northeast Ohio revealed a novel recombination event between Salmonella and P. aeruginosa, heralding a new antibiotic resistance threat in this region's health care system.

Article

Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research A National Heart, Lung, and Blood Institute Workshop Report

by George A. Mensah; Richard S. Cooper; Anna Maria Siega-Riz; Lisa A. Cooper; Justin D. Smith; C. Hendricks Brown; John M. Westfall; Elizabeth O. Ofili; LeShawndra N. Price; Sonia Arteaga; Melissa Green Parker; Cheryl R. Nelson; Brad J. Newsome; Nicole Redmond; Rebecca A. Roper; Bettina M. Beech; Jada L. Brooks; Debra Furr-Holden; Samson Y. Gebreab; Wayne H. Giles; Regina Smith James; Tene Lewis; Ali H. Mokdad; Kari D. Moore; Joseph E. Ravenell; Al Richmond; Nancy E. Schoenberg; Mario Sims; Gopal K. Singh; Anne E. Sumner; Roberto P. Trevino; Karriem S. Watson; M. Larissa Aviles-Santa; Jared P. Reis; Charlotte A. Pratt; Michael M. Engelgau; David C. Goff Jr.; Eliseo J. Perez-Stable

2018

Subjects
  • Geography
  • Health Sciences, Public Health
  • Sociology, Demography
  • File Download
  • View Abstract

Abstract:Close

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-Area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.

Article

Population Snapshot of Invasive Serogroup B Meningococci in South Africa from 2005 to 2008

by Mignon du Plessis; Chivonne Moodley; Kedibone M. Mothibeli; Azola Fali; Keith Klugman; Anne Von Gottberg

2012

Subjects
  • Biology, Microbiology
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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In South Africa, serogroup B meningococcal disease is sporadic. The aim of this study was to characterize serogroup B strains causing invasive meningococcal disease (IMD) in South Africa from 2005 to 2008. Isolates, collected through a national, laboratory-based surveillance program for IMD, were characterized by multilocus sequence typing (MLST). Two thousand two hundred thirty-four cases were reported, of which 1,447 had viable isolates. Intermediate resistance to penicillin was observed in 2.8% (41/1,447) of all strains. Serogroup B was the second most common serogroup (17%, 251/1,447) and increased from 14% (58/414) in 2005 to 25% (72/290) in 2008 (P < 0.001); however, incidence remained stable during the study period (average incidence, 0.13/100,000 population) (P=0.54). Serogroup B was predominantly characterized by three clonal complexes, namely, ST-41/44/lineage 3, ST-32/ET-5, and the new complex ST-4240/6688, which accounted for 27% (65/242), 23% (55/242), and 16% (38/242) of isolates, respectively. ST-4240/6688 was more prevalent among young children ( < 5 years) than other clonal complexes (27/37 [73%] versus 108/196 [55%] ; P=0.04). In the most densely populated province of South Africa, Gauteng, the prevalence of ST-32/ET-5 increased from 8% (2/24) in 2005 to 38% (9/24) in 2008 (P=0.04). Capsular switching was observed in 8/242 (3%) strains. The newly assigned clonal complex ST-4240/6688 was more common in young children.

Article

Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

by Daniel E. Dulek; Dawn C. Newcomb; Kasia Goleniewska; Jaqueline Cephus; Weisong Zhou; Sara Reiss; Shinji Toki; Fei Ye; Rinat Zaynagetdinov; Taylor P. Sherrill; Timothy S. Blackwell; Martin Moore; Kelli L. Boyd; Jay K. Kolls; R. Stokes Peebles

2014

Subjects
  • Health Sciences, Immunology
  • Biology, Microbiology
  • Biology, Biostatistics
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The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

Article

Population Snapshot of Streptococcus pneumoniae Causing Invasive Disease in South Africa Prior to Introduction of Pneumococcal Conjugate Vaccines

by Kedibone M. Ndlangisa; Mignon du Plessis; Nicole Wolter; Linda de Gouveia; Keith Klugman; Anne von Gottberg

2014

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Pathology
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We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD) prior to routine use of pneumococcal conjugate vaccines (PCV) in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60%) from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ≥5 years) was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC) 217, 98% of all serotype 1] and 14 [CC230, 43%)]), some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]). In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively). Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12) and 64% (9/14) of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction. Copyright:

Article

PrEP Eligibility and Interest Among Clinic- and Community-Recruited Young Black Women in Atlanta, Georgia, USA

by Jessica Sales; Riley Steiner; JL Brown; Andrea Swartzendruber; AS Patel; Anandi Sheth

2018

Subjects
  • Health Sciences, Immunology
  • Biology, Virology
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Background: Atlanta has been identified as an HIV “hot spot” for Black women and ranks 5 th in the US with new infections. Yet little is known about PrEP eligibility or interest among young Black women in Atlanta. Methods: A convenience sample of 1,261 Black women (ages 14-24 years) were recruited from two settings: community venues and sexual health clinics. They provided self-reported sexual behavior data and specimens for laboratory testing for chlamydia (CT) and gonorrhea (GC) infections. For each woman, the number of key self-reported behavioral HIV risk factors was calculated (0-6 factors for the clinic sample, 0-3 factors for the community sample). A single item assessed PrEP interest in the community sample only. Results: Bacterial STI positivity, an indicator for PrEP eligibility, was 20.5% (17.1% CT, 6.3% GC) and 20.9% (18.8% CT, 5.2% GC) for the clinic and community samples, respectively. Of the 144 STI positive women from the clinic sample, 20.1% reported no behavioral risk indicators and 47.2% reported > 2 behavioral indicators. Of the 117 STI positive women from the community sample, 21.4% reported no behavioral risk indicators. 60.7% of the community sample reported they would be likely or very likely to use PrEP if available. Conclusion: Young Black women in Atlanta, whether sampled from community or sexual health settings, are at substantial risk for HIV infection and meet several PrEP eligibility criteria. Scaling up PrEP among women in Atlanta could have significant implications for HIV in this high burden region.

Article

Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients: Prolonged RNA Detection in Whole Blood

by Hana M El Sahly; Rodion Gorchakov; Lilin Lai; Muktha S Natrajan; Shital M Patel; Robert L Atmar; Wendy A Keitel; Daniel F Hoft; Jill Barrett; Jason Bailey; Srilatha Edupuganti; Vanessa Raabe; Henry Wu; Jessica Fairley; Nadine Rouphael; Kristy O Murray; Mark Mulligan

2019

Subjects
  • Health Sciences, Immunology
  • Biology, Microbiology
  • Biology, Cell
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Background. Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods. US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naive cases were also compared. Results. We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65-79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus- experienced cases than naive ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells. Conclusions. ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.

Article

Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice

by Wilson C. Fok; Yiqiang Zhang; Adam B. Salmon; Arunabh Bhattacharya; Rakesh Gunda; Dean Jones; Walter Ward; Kathleen Fisher; Arlan Richardson; Viviana I. Perez

2013

Subjects
  • Biology, Physiology
  • Biology, Cell
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Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin.

Article

Child, Household, and Caregiver Characteristics Associated with Hospitalization for Influenza Among Children 6-59 Months of Age An Emerging Infections Program Study

by Nila J. Dharan; Leslie Z. Sokolow; Po-Yung Cheng; Paul Gargiullo; Ken Gershman; Ruth Lynfield; Craig Morin; Ann Thomas; James Meek; Monica Farley; Katherine E. Arnold; Art Reingold; Allen S. Craig; William Schaffner; Nancy M. Bennett; Shelley Zansky; Joan Baumbach; Sarah Lathrop; Laurie Kamimoto; David K. Shay

2014

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
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BACKGROUND: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites. METHODS: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. RESULTS: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age < 26 years [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1-2.9]; household income below the poverty threshold (OR: 2.2, 95% CI: 1.4-3.6); smoking by > 50% of household members (OR: 2.9, 95% CI: 1.4-6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2-2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5-31.0), pulmonary (OR: 2.9, 95% CI: 1.9-4.4) and neurologic (OR: 3.8, 95% CI: 1.6-9.2) conditions. Full influenza immunization decreased the risk among children 6-23 months of age (OR: 0.5, 95% CI: 0.3-0.9) but not among those 24-59 months of age (OR: 1.5, 95% CI: 0.8-3.0; P value for difference = 0.01). CONCLUSIONS: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.
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