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Find video protocols related to scientific articles indexed in Pubmed.
End Stage Renal Disease Among HIV-Infected Adults in North America.
Clin. Infect. Dis.
PUBLISHED: 11-20-2014
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?HIV-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.
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Estimating future trends in paediatric HIV.
AIDS
PUBLISHED: 11-20-2014
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Paediatric treatment continues to lag behind adult treatment and significant efforts are urgently needed to scale up antiretroviral therapy (ART) for children. As efforts to prevent mother-to-child transmission expand, better understanding of future trends and age characterization of the population that will be in need of ART is needed to inform policymakers, as well as drug developers and manufacturers.
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Association of Geographic and Seasonal Variation With Diverticulitis Admissions.
JAMA Surg
PUBLISHED: 11-20-2014
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The incidence of diverticulitis has been associated with geographic and seasonal variation. Low levels of circulating vitamin D are associated with diverticulitis. We investigated the association between UV light and diverticulitis.
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Dynamic two-photon imaging of the immune response to Toxoplasma gondii infection.
Parasite Immunol.
PUBLISHED: 11-20-2014
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Toxoplasma gondii is a highly successful parasite that can manipulate host immune responses to optimise its persistence and spread. As a result, a highly complex relationship exists between T. gondii and the immune system of the host. Advances in imaging techniques, and in particular, the application of two-photon microscopy to mouse infection models, has made it possible to directly visualize interactions between parasites and the host immune system as they occur in living tissues. Here we will discuss how dynamic imaging techniques have provided unexpected new insight into (1) how immune responses are dynamically regulated by cells and structures in the local tissue environment, (2) how protective responses to T. gondii are generated, and (3) how the parasite exploits the immune system for its own benefit. This article is protected by copyright. All rights reserved.
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Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3,4-d]pyrimidines.
Org. Biomol. Chem.
PUBLISHED: 11-20-2014
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Fused pyrimidine cores are privileged kinase scaffolds, yet few examples of the 2-amino-pyrido[3,4-d]pyrimidine chemotype have been disclosed in the context of kinase inhibitor programs. Furthermore, no general synthetic route has been reported to access 2-amino-pyrido[3,4-d]pyrimidine derivatives. Here we report a versatile and efficient chemical approach to this class of molecules. Our strategy involves the concise preparation of 8-chloro-2-(methylthio)pyrido[3,4-d]pyrimidine intermediates and their efficient derivatisation to give novel compounds with potential as kinase inhibitors.
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Educating Health Care Professionals on Human Trafficking.
Pediatr Emerg Care
PUBLISHED: 11-20-2014
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The US Department of State estimates that there are between 4 and 27 million individuals worldwide in some form of modern slavery. Recent studies have demonstrated that 28% to 50% of trafficking victims in the United States encountered health care professionals while in captivity, but were not identified and rescued. This study aimed to determine whether an educational presentation increased emergency department (ED) providers' recognition of human trafficking (HT) victims and knowledge of resources to manage cases of HT.
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Omega-3 Fatty acids and stress-induced immune dysregulation: implications for wound healing.
Mil Med
PUBLISHED: 11-06-2014
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Stress-related immune alterations can be consequential for health; they can enhance susceptibility to infectious agents and influence the severity of infectious disease, diminish the strength of immune responses to vaccines, reactivate latent viruses, and slow wound healing. Furthermore, stressful events and negative emotions promote systemic proinflammatory cytokine production while reducing beneficial local production of proinflammatory cytokines at the wound site that are important for wound healing. Dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) also influence systemic inflammation; high proportions of omega-6 to omega-3 boost inflammation, while omega-3 has anti-inflammatory properties. Additionally, the limited evidence thus far suggests that omega-3 PUFA may enhance local inflammatory responses at wound sites. Moreover, an individual's dietary proportion of omega-3 to omega-6 may influence the magnitude of inflammatory responses to stressful events. Thus, wound healing and surgery provide exemplars of how stress and depression can interact with the diet to influence important clinical outcomes.
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Elevated Levels of Monocyte Activation Markers Are Associated with Subclinical Atherosclerosis in HIV-Infected and -Uninfected Men.
J. Infect. Dis.
PUBLISHED: 11-02-2014
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?Heightened immune activation among HIV-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and CD14 (sCD14), and monocyte chemoattractant protein-1 (CCL2), with subclinical atherosclerosis among HIV-infected and -uninfected men in the Multicenter AIDS Cohort Study.
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Level of Adherence and HIV RNA Suppression in the Current Era of Highly Active Antiretroviral Therapy (HAART).
AIDS Behav
PUBLISHED: 10-25-2014
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The need to achieve ?95 % adherence to HAART for treatment effectiveness may be a barrier for universal initiation at early stages of HIV. Using longitudinal data collected from 2006 to 2011 from cohort studies of MSM (MACS) and IDUs (ALIVE study), we estimated the minimum adherence needed to achieve HIV RNA suppression (<50 copies/mL), defined as the level at which at least 80 % were virally suppressed, and the odds of suppression was not significantly different than that observed with ?95 % adherence. In the MACS, ?80 % suppression was observed with 80-84 % adherence and the odds ratio for suppression (vs. ?95 % adherence) was 1.43 (0.61, 3.33). In the ALIVE study where <35 % were on newer drugs, only 71.4 % were suppressed among those who reported ?95 % adherence. Although IDUs on older HAART regimens may need to be ?95 % adherent, concerns related to non-adherence may be less of a barrier to initiation of modern HAART regimens.
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Filovirus RefSeq entries: evaluation and selection of filovirus type variants, type sequences, and names.
Viruses
PUBLISHED: 09-17-2014
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Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information's (NCBI's) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences.
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Prostate cancer risk prediction based on complete prostate cancer family history.
Prostate
PUBLISHED: 09-02-2014
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Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history.
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Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus.
PLoS Negl Trop Dis
PUBLISHED: 07-01-2014
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Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection.
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Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.
BMC Genomics
PUBLISHED: 06-20-2014
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Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods.
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Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China.
Cancer Prev Res (Phila)
PUBLISHED: 06-09-2014
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Broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can generate the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases (GST) and other cytoprotective enzymes. A broccoli sprout-derived beverage providing daily doses of 600 ?mol glucoraphanin and 40 ?mol sulforaphane was evaluated for magnitude and duration of pharmacodynamic action in a 12-week randomized clinical trial. Two hundred and ninety-one study participants were recruited from the rural He-He Township, Qidong, in the Yangtze River delta region of China, an area characterized by exposures to substantial levels of airborne pollutants. Exposure to air pollution has been associated with lung cancer and cardiopulmonary diseases. Urinary excretion of the mercapturic acids of the pollutants, benzene, acrolein, and crotonaldehyde, were measured before and during the intervention using liquid chromatography tandem mass spectrometry. Rapid and sustained, statistically significant (P ? 0.01) increases in the levels of excretion of the glutathione-derived conjugates of benzene (61%), acrolein (23%), but not crotonaldehyde, were found in those receiving broccoli sprout beverage compared with placebo. Excretion of the benzene-derived mercapturic acid was higher in participants who were GSTT1-positive than in the null genotype, irrespective of study arm assignment. Measures of sulforaphane metabolites in urine indicated that bioavailability did not decline over the 12-week daily dosing period. Thus, intervention with broccoli sprouts enhances the detoxication of some airborne pollutants and may provide a frugal means to attenuate their associated long-term health risks.
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Effects of stress and depression on inflammatory immune parameters in pregnancy.
Am. J. Obstet. Gynecol.
PUBLISHED: 06-04-2014
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There is a substantial body of literature that links psychological stress to adverse pregnancy outcomes, particularly preterm birth. Comparatively few studies have examined potential biologic mechanisms that explain these associations. Attention to inflammatory processes is warranted. This article describes emerging studies that demonstrate that, as in nonpregnant humans and animals, psychological stress and distress (ie, depressive symptoms) predict dysregulation of inflammatory processes in human pregnancy. This includes elevations in circulating inflammatory cytokines, exaggerated inflammatory responses to in vivo biologic challenges, and more robust inflammatory responses to psychological challenges. Continued research in this area is needed to determine the implications of such stress-induced immune dysregulation for birth outcomes and for maternal health and fetal development.
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Full-genome sequence of human betacoronavirus 2c jordan-n3/2012 after serial passage in Mammalian cells.
Genome Announc
PUBLISHED: 05-31-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiologic agent of a highly lethal pneumonia. Here, we report the full-genome sequence of the Jordan-N3/2012 strain after serial passage in two distinct mammalian cell lines. The genome exhibits noteworthy stability, which may inform the development of vaccines and therapeutics used to treat infection with this virus.
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A longitudinal follow-up study of affect in children and adults with Cornelia de Lange syndrome.
Am J Intellect Dev Disabil
PUBLISHED: 05-30-2014
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Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N ?=? 67), cri du chat syndrome (CdCS; N ?=? 42), and Fragile X syndrome (FXS; N ?=? 142) completed the Mood, Interest and Pleasure Questionnaire (MIPQ) at Time 1 and 2 years later (Time 2). Scores on the MIPQ were significantly lower in the CdLS group compared with the CdCS and FXS groups at Time 1 and Time 2. Lower MIPQ scores were characteristic of older adolescents (> 15 years) and adults with CdLS. However, there were no significant differences in MIPQ scores between Time 1 and Time 2. Age and insistence on sameness predicted MIPQ scores in CdLS.
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Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection.
Antimicrob. Agents Chemother.
PUBLISHED: 05-19-2014
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Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.
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Epicardial fat is associated with duration of antiretroviral therapy and coronary atherosclerosis.
AIDS
PUBLISHED: 05-10-2014
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Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and antiretroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine whether HIV infection is associated with greater epicardial fat and whether epicardial fat is associated with subclinical coronary atherosclerosis.
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Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells.
Antiviral Res.
PUBLISHED: 04-23-2014
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Antigen presenting cells (APCs), including macrophages and dendritic cells, are early and sustained targets of Ebola virus (EBOV) infection in vivo. Because EBOV activates mitogen-activated protein kinase (MAPK) signaling upon infection of APCs, we evaluated the effect of pyridinyl imidazole inhibitors of p38 MAPK on EBOV infection of human APCs and EBOV mediated cytokine production from human DCs. The p38 MAPK inhibitors reduced viral replication in PMA-differentiated macrophage-like human THP-1 cells with an IC50 of 4.73?M (SB202190), 8.26?M (p38kinhIII) and 8.21?M (SB203580) and primary human monocyte-derived dendritic cells (MDDCs) with an IC50 of 2.67?M (SB202190). Furthermore, cytokine production from EBOV-treated MDDCs was inhibited in a dose-dependent manner. A control pyridinyl imidazole compound failed to inhibit either EBOV infection or cytokine induction. Using an established EBOV virus-like particle (VLP) entry assay, we demonstrate that inhibitor pretreatment blocked VLP entry suggesting that the inhibitors blocked infection and replication at least in part by blocking EBOV entry. Taken together, our results indicate that pyridinyl imidazole p38 MAPK inhibitors may serve as leads for the development of therapeutics to treat EBOV infection.
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Associations between HIV infection and subclinical coronary atherosclerosis.
Ann. Intern. Med.
PUBLISHED: 04-02-2014
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Coronary artery disease (CAD) has been associated with HIV infection, but data are not consistent.
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HIV therapy, metabolic and cardiovascular health are associated with glomerular hyperfiltration among men with and without HIV infection.
AIDS
PUBLISHED: 03-28-2014
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Diabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men.
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A novel approach for successful closure of sinonasal fistulae.
J Plast Reconstr Aesthet Surg
PUBLISHED: 03-15-2014
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Medial canthus sinonasal fistula is associated with troublesome aesthetic and functional issues. Corneal irritation and drying results from escape of both air and secretions from the nasal cavity across the ocular surface as well as misting of spectacles if worn. Reconstruction of such fistulae is associated with a high rate of recurrence and thus presents a difficult surgical challenge.
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The NIAID Integrated Research Facility at Frederick, Maryland: a unique international resource to facilitate medical countermeasure development for BSL-4 pathogens.
Pathog Dis
PUBLISHED: 03-14-2014
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Scientists at the National Institute of Allergy and Infectious Diseases Integrated Research Facility at Fort Detrick, Frederick, Maryland, coordinate and facilitate preclinical research on infectious diseases to develop medical countermeasures for high-consequence pathogens. This facility is unique in that it is the only maximum containment laboratory in the world where conventional and molecular medical imaging equipments are incorporated into the design of the facility. This capability provides investigators with unique tools to dissect disease pathogenesis, evaluate the ability of animal models to recapitulate human disease, and test candidate countermeasures. Importantly, advanced molecular imaging has the potential to provide alternative endpoints to lethality. Using these alternative endpoints, investigators can reduce the number of animals used in experiments and evaluate countermeasures in sublethal models. With the incorporation of medical imaging modalities, a clinical laboratory modeled after those existing in hospitals, and a highly trained veterinary medicine team, IRF-Frederick is uniquely suited to advance our understanding of emerging infectious diseases and to facilitate the development of medical countermeasures and clinical care paradigms previously considered impossible.
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Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia.
MBio
PUBLISHED: 02-27-2014
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The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats. IMPORTANCE This study was undertaken to determine the historical and current prevalence of Middle East respiratory syndrome (MERS) coronavirus infection in dromedary camels and other livestock in the Kingdom of Saudi Arabia, where the index case and the majority of cases of MERS have been reported.
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Comparison of racial differences in plaque composition and stenosis between HIV-positive and HIV-negative men from the Multicenter AIDS Cohort Study.
Am. J. Cardiol.
PUBLISHED: 02-23-2014
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Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed <136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis >50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis >50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.
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Children and the Patient Protection and Affordable Care Act: opportunities and challenges in an evolving system.
Acad Pediatr
PUBLISHED: 02-12-2014
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The Patient Protection and Affordable Care Act (ACA), passed in 2010, focused primarily on the problems of adults, but the changes in payment for and delivery of care it fosters will likely impact the health care of children. The evolving epidemiology of pediatric illness in the United States has resulted in a relatively small population of medically fragile children dispersed through the country and a large population of children with developmental and behavioral health issues who experience wide degrees of health disparities. Review of previous efforts to change the health care system reveals specific innovations in child health delivery that have been designed to address issues of child health. The ACA is complex and contains some language that improves access to care, quality of care, and the particular needs of the pediatric workforce. Most of the payment models and delivery systems proposed in the ACA, however, were not designed with the needs of children in mind and will need to be adapted to address their needs. To assure that the needs of children are met as systems evolve, child health professionals within and outside academe will need to focus their efforts in clinical care, research, education, and advocacy to incorporate child health programs into changing systems and to prevent unintended harm to systems designed to care for children.
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Systems kinomics for characterizing host responses to high-consequence pathogens at the NIH/NIAID Integrated Research Facility-Frederick.
Pathog Dis
PUBLISHED: 02-04-2014
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Currently, there is a paucity of information regarding the molecular pathogenesis for many high-consequence pathogens (HCPs) that pose threats to both national and international public health. In spite of this, investigations of the molecular pathogenesis for many HCPs have been limited to gross pathological changes in animal models or global analysis of gene expression. Further, questions remain regarding the ability of animal models of disease to recapitulate human molecular pathogenesis or act as predictors of therapeutic efficacy. Thus, it is likely that medical countermeasure development for HCPs will rely on identifying therapeutic targets that are uniquely modulated during HCP infection. It is also appreciated that many cellular processes can be regulated independently of changes in transcription or translation through phosphorylation events. Cellular kinases, individually or collectively (the kinome), play critical roles in regulating complex biology, underlie various malignancies, and represent high-priority drug targets. The growing interest in kinases in both basic and translational research has driven efforts to develop technologies that enable characterization of phosphorylation-mediated signal transduction. To this end, enhanced technical capabilities at the IRF-Frederick provide the unique capability for characterizing host responses to HCP insult during the course of infection and identify novel targets for therapeutic intervention.
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The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection.
PLoS Pathog.
PUBLISHED: 02-01-2014
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The genus Orthopoxviridae contains a diverse group of human pathogens including monkeypox, smallpox and vaccinia. These viruses are presumed to be less dependent on host functions than other DNA viruses because they have large genomes and replicate in the cytoplasm, but a detailed understanding of the host factors required by orthopoxviruses is lacking. To address this topic, we performed an unbiased, genome-wide pooled RNAi screen targeting over 17,000 human genes to identify the host factors that support orthopoxvirus infection. We used secondary and tertiary assays to validate our screen results. One of the strongest hits was heat shock factor 1 (HSF1), the ancient master regulator of the cytoprotective heat-shock response. In investigating the behavior of HSF1 during vaccinia infection, we found that HSF1 was phosphorylated, translocated to the nucleus, and increased transcription of HSF1 target genes. Activation of HSF1 was supportive for virus replication, as RNAi knockdown and HSF1 small molecule inhibition prevented orthopoxvirus infection. Consistent with its role as a transcriptional activator, inhibition of several HSF1 targets also blocked vaccinia virus replication. These data show that orthopoxviruses co-opt host transcriptional responses for their own benefit, thereby effectively extending their functional genome to include genes residing within the host DNA. The dependence on HSF1 and its chaperone network offers multiple opportunities for antiviral drug development.
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Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo.
Emerging Infect. Dis.
PUBLISHED: 01-25-2014
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Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance.
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Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV infection.
Antivir. Ther. (Lond.)
PUBLISHED: 01-21-2014
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We sought to determine whether markers of systemic inflammation are associated with the presence of moderate-to-severe obstructive sleep apnea (OSA), and whether this association differs based on HIV and HIV treatment status.
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Increases in duration of first highly active antiretroviral therapy over time (1996-2009) and associated factors in the Multicenter AIDS Cohort Study.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-15-2014
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Antiretroviral therapy (ART) regimens changes occur frequently among HIV-infected persons. Duration and type of initial highly active antiretroviral therapy (HAART) and factors associated with regimen switching were evaluated in the Multicenter AIDS Cohort Study.
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[Relational and Reproductive Trajectories Leading to Adolescent Pregnancy in Portugal: a National and Regional Characterization.]
Acta Med Port
PUBLISHED: 01-14-2014
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Introduction: The current study aimed to describe the relational and reproductive trajectories leading to adolescent pregnancy in Portugal, and to explore whether there were differences in this process according to adolescents' place of residence.Material and Methods: Data were collected between 2008 and 2013 in 42 public health services using a self-report questionnaire developed by the researchers. The sample consisted of a nationally representative group of pregnant adolescents (n = 459).Results: Regardless of having had one (59.91%) or multiple sexual partners (40.09%), the majority of adolescents became pregnant in a romantic relationship, using contraception at the time of the conception and knowing the contraceptive failure which led to pregnancy (39.22%). In some regions other trajectories were highly prevalent, reflecting options such as planning the pregnancy (Alentejo Region/ Azores Islands), not using contraception (Centro Region/Madeira Islands) or using it incorrectly, without identifying the contraceptive failure (Madeira Islands). On average, romantic relationships were longer than 19 months and adolescents' partners were older than themselves (> 4 years) and no longer in school (75.16%); these results were particularly significant when the pregnancy was planned.Discussion: The knowledge gained in this study shows that prevention efforts must be targeted according to the adolescents' needs in each region and should include high-risk male groups.Conclusion: Our results may enable more efficient health policies to prevent adolescent pregnancy in different country regions and support educators and health care providers on sexual education and family planning efforts.
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Lower adiponectin is associated with subclinical cardiovascular disease among HIV-infected men.
AIDS
PUBLISHED: 01-10-2014
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To examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.
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Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: Effects of maternal body mass index.
Cytokine
PUBLISHED: 01-09-2014
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The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated.
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Optimizing benefits of influenza virus vaccination during pregnancy: potential behavioral risk factors and interventions.
Vaccine
PUBLISHED: 01-03-2014
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Pregnant women and infants are at high risk for complications, hospitalization, and death due to influenza. It is well-established that influenza vaccination during pregnancy reduces rates and severity of illness in women overall. Maternal vaccination also confers antibody protection to infants via both transplacental transfer and breast milk. However, as in the general population, a relatively high proportion of pregnant women and their infants do not achieve protective antibody levels against influenza virus following maternal vaccination. Behavioral factors, particularly maternal weight and stress exposure, may affect initial maternal antibody responses, maintenance of antibody levels over time (i.e., across pregnancy), as well as the efficiency of transplacental antibody transfer to the fetus. Conversely, behavioral interventions including acute exercise and stress reduction can enhance immune protection following vaccination. Such behavioral interventions are particularly appealing in pregnancy because they are safe and non-invasive. The identification of individual risk factors for poor responses to vaccines and the application of appropriate interventions represent important steps towards personalized health care.
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CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
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Maternal Obesity Is Associated with Alterations in the Gut Microbiome in Toddlers.
PLoS ONE
PUBLISHED: 01-01-2014
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Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18-27 months of age (n?=?77) were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES). In the higher SES group (n?=?47), children of obese (BMI?30) versus non-obese mothers clustered on a principle coordinate analysis (PCoA) and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course.
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Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis.
Microbiome
PUBLISHED: 01-01-2014
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Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required.
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Sleep disordered breathing, fatigue, and sleepiness in HIV-infected and -uninfected men.
PLoS ONE
PUBLISHED: 01-01-2014
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We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness.
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Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.
PLoS ONE
PUBLISHED: 01-01-2014
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The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.
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Factors affecting glomerular filtration rate, as measured by iohexol disappearance, in men with or at risk for HIV infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD).
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Asthma, tobacco smoke and the indoor environment: a qualitative study of sheltered homeless families.
J Asthma
PUBLISHED: 11-22-2013
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Abstract Objective: Asthma is common in homeless children with an incidence of 28-40%. There are few published studies investigating asthma in homeless children. This study examines the perspectives of both caregivers and shelter staff regarding challenges and opportunities of caring for children with asthma. Methods: A focus group of sheltered parents (n?=?10) with children who have asthma was conducted to identify barriers to optimal asthma management. Key informant interviews (n?=?6) were conducted with shelter staff to discuss the shelter systems and policies to address childhood asthma. Data were audio-recorded and transcribed. A representative analysis team performed qualitative theme analysis. Results: Key themes across 5 domains were identified: asthma education, access to asthma medication and equipment, asthma action plans, structural barriers to asthma management and environmental triggers. Parents identified multiple asthma triggers present in the shelter environment but cited lack of control as a barrier to remediation. Shelter staff desired elimination of asthma triggers but refer to the lack of resources as the primary barrier. Shelter staff favored a smoking ban on shelter property but named challenges to policy implementation. Both parents and staff identified asthma education and increased access to medications would be helpful. Conclusions: Policies to reduce environmental exposures, such as a smoking ban, to asthma triggers has the potential to improve the health of sheltered children with asthma.
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Serum Levels of Cytokines, and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B cell Lymphoma Risk.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 11-12-2013
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Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF? were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF? may serve as biomarkers for AIDS-NHL.
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Age, Comorbidities, and AIDS Predict a Frailty Phenotype in Men Who Have Sex With Men.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-14-2013
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Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men.
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Nonhuman transferrin receptor 1 is an efficient cell entry receptor for ocozocoautla de espinosa virus.
J. Virol.
PUBLISHED: 10-09-2013
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Ocozocoautla de Espinosa virus (OCEV) is a novel, uncultured arenavirus. We found that the OCEV glycoprotein mediates entry into grivet and bat cells through transferrin receptor 1 (TfR1) binding but that OCEV glycoprotein precursor (GPC)-pseudotyped retroviruses poorly entered 53 human cancer cell lines. Interestingly, OCEV and Tacaribe virus could use bat, but not human, TfR1. Replacing three human TfR1 amino acids with their bat ortholog counterparts transformed human TfR1 into an efficient OCEV and Tacaribe virus receptor.
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A microbial profiling method for the human microbiota using high-throughput sequencing.
Metagenomics (Cairo)
PUBLISHED: 09-10-2013
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Study of the human microbiota in relation to human health and disease is a rapidly expanding field. To fully understand the complex relationship between the human gut microbiota and disease risks, study designs that capture the variation within and between human subjects at the population level are required, but this has been hampered by the lack of cost-effective methods to characterize this variation. Illumina sequencing is inexpensive and produces millions of reads per run, but it is unclear whether short reads can adequately represent the microbial community of a human host. In this study, we examined the utility of a profiling method, microbial nucleotide signatures (MNS), focused on low-depth sampling of the human microbiota using Ilumina short reads. This method is intended to aid in human population-based studies where large sample sizes are required to adequately capture variation in disease or phenotype differences. We found that, by calculating the nucleotide diversities along the sequenced 16S rRNA gene region, which did not require assembly or phylogenetic identification, we were able to differentiate the gut microbial nucleotide signatures of 9 healthy individuals. When we further subsampled the reads down to 40,000 reads (51 bp long) per sample, the diversity profiles were relatively unchanged. Applying MNS to a public datasets showed that it could differentiate body site differences. The scalability of our approach offers rapid classification of study participants for studies with the sample sizes required for epidemiological studies. Using MNS to classify the microbiome associated with a disease state followed by targeted in-depth sequencing will give a comprehensive understanding of the role of the microbiome in human health.
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Updates in diverticular disease.
Curr Gastroenterol Rep
PUBLISHED: 09-10-2013
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Diverticulosis and its major complications, diverticulitis and diverticular bleeding, are increasingly common indications for hospitalization and outpatient visits. Recent publications in the field of diverticular disease have challenged long-standing disease concepts and management strategies. This article will highlight studies which have helped to clarify the contribution of genetic factors, fiber consumption and medication use to the development of diverticular disease, the role of antibiotics in the treatment of acute diverticulitis, and the association between diverticulitis, irritable bowel syndrome, and colon cancer.
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Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China.
Cancer Prev Res (Phila)
PUBLISHED: 08-20-2013
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Primary liver cancer (PLC) is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Although synergistic interactions between these two risk factors have been observed in cohort studies in China, here we determined the impact of agricultural reforms in the 1980s leading to diminished maize consumption and implementation of subsidized universal vaccination against HBV in the 2000s on PLC primary prevention. A population-based cancer registry was used to track PLC mortality in Qidong, China and was compared with the timeline of HBV immunization. Randomly selected serum samples from archived cohort collections from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50% reductions in PLC mortality rates occurred across birth cohorts from the 1960s to the 1980s for Qidongese less than 35 years of age although all were born before universal vaccination of newborns. Median levels of the aflatoxin biomarker decreased from 19.3 pg/mg albumin in 1989 to undetectable (<0.5 pg/mg) by 2009. A population attributable benefit of 65% for reduced PLC mortality was estimated from a government-facilitated switch of dietary staple from maize to rice; 83% of this benefit was in those infected with HBV. Food policy reforms in China resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in place augurs even greater risk reductions in the future.
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Diverticular Disease Is Associated with Increased Risk of Subsequent Arterial and Venous Thromboembolic Events.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 08-19-2013
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Diverticular disease and cardiovascular disease share several risk factors. Inflammation associated with diverticular disease could predispose to cardiovascular disease. We assessed the association between a diagnosis of diverticular disease and subsequent arterial and venous thromboembolic events, adjusting for related comorbidities to explore a possible causal relationship.
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Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA.
Arch. Virol.
PUBLISHED: 07-24-2013
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Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, (/)///-, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.
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Legislative Advocacy: Evaluation of a Grand Rounds Intervention for Pediatricians.
Acad Pediatr
PUBLISHED: 07-22-2013
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To evaluate the impact of a Grand Rounds Action Alert (GRAA) intervention on the behaviors, knowledge, and attitudes of pediatric grand rounds (GR) attendees; and to assess its acceptability.
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Stress-induced inflammatory responses in women: effects of race and pregnancy.
Psychosom Med
PUBLISHED: 07-19-2013
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African Americans experience preterm birth at nearly twice the rate of whites. Chronic stress associated with minority status is implicated in this disparity. Inflammation is a key biological pathway by which stress may affect birth outcomes. This study examined the effects of race and pregnancy on stress-induced inflammatory responses.
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Antiretroviral therapy-induced changes in plasma lipids and the risk of kidney dysfunction in HIV-infected men.
AIDS Res. Hum. Retroviruses
PUBLISHED: 07-09-2013
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In the context of HIV, the initiation of effective antiretroviral therapy (ART) has been found to increase the risk of dyslipidemia in HIV-infected individuals, and dyslipidemia has been found to be a risk factor for kidney disease in the general population. Therefore, we examined changes in lipid profiles in HIV-infected men following ART initiation and the association with future kidney dysfunction. HIV-infected men from the Multicenter AIDS Cohort Study initiating ART between December 31, 1995 and September 30, 2011 with measured lipid and serum creatinine values pre-ART and post-ART were selected. The associations between changes in total cholesterol or high-density lipoprotein following ART initiation and the estimated change in glomerular filtration rate (eGFR) over time were assessed using piecewise linear mixed effects models. There were 365 HIV-infected men who contributed to the analysis. In the adjusted models, at 3 years post-ART, those with changes in total cholesterol >50 mg/dl had an average decrease in eGFR of 2.6 ml/min/1.73 m(2) per year (p<0.001) and at 5 years post-ART, the average decrease was 2.4 ml/min/1.73 m(2) per year (p=0.008). This decline contrasted with the estimates for those with changes in total cholesterol ? 50 mg/dl: 1.4 ml/min/1.73 m(2) decrease per year (p<0.001) and 0.1 ml/min/1.73 m(2) decrease per year (p=0.594) for the same time periods, respectively. Large decreases in high-density lipoprotein (a decline of greater than 5 mg/dl) were not associated with declines in eGFR. These results indicate that large ART-related increases in total cholesterol may be a risk factor for kidney function decline in HIV-infected men. Should these results be generalizable to the broader HIV population, monitoring cholesterol changes following the initiation of ART may be important in identifying HIV-infected persons at risk for kidney disease.
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Prevalence and molecular characterisation of Eimeria species in Ethiopian village chickens.
BMC Vet. Res.
PUBLISHED: 06-26-2013
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Coccidiosis, caused by species of the apicomplexan parasite Eimeria, is a major disease of chickens. Eimeria species are present world-wide, and are ubiquitous under intensive farming methods. However, prevalence of Eimeria species is not uniform across production systems. In developing countries such as Ethiopia, a high proportion of chicken production occurs on rural smallholdings (i.e. village chicken production) where infectious diseases constrain productivity and surveillance is low. Coccidiosis is reported to be prevalent in these areas. However, a reliance on oocyst morphology to determine the infecting species may impede accurate diagnosis. Here, we used cross-sectional and longitudinal studies to investigate the prevalence of Eimeria oocyst shedding at two rural sites in the Ethiopian highlands.
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FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection.
Sci Transl Med
PUBLISHED: 06-21-2013
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Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)- and ex-US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections.
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Self-rated health among pregnant women: associations with objective health indicators, psychological functioning, and serum inflammatory markers.
Ann Behav Med
PUBLISHED: 06-15-2013
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Biobehavioral correlates of self-rated health in pregnancy are largely unknown.
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Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis.
J. Cyst. Fibros.
PUBLISHED: 06-06-2013
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Iron supplementation for hypoferremic anemia could potentiate bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing this hypothesis are lacking.
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Joint effects of alcohol consumption and high-risk sexual behavior on HIV seroconversion among men who have sex with men.
AIDS
PUBLISHED: 05-31-2013
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To estimate the effects of alcohol consumption and number of unprotected receptive anal intercourse partners on HIV seroconversion while appropriately accounting for time-varying confounding.
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Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis.
J. Immunol.
PUBLISHED: 05-22-2013
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Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from cystic fibrosis (CF) transmembrane conductance regulator(-/-) mice have impaired function, no study has investigated primary alveolar macrophages in adults with CF. CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from eight CF subjects and eight healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared with control subjects. CF subjects had lower serum and BAL IGF-1 levels compared with healthy control subjects. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, whereas IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment.
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A candidate gene approach for virally induced cancer with application to HIV-related Kaposis sarcoma.
Int. J. Cancer
PUBLISHED: 04-22-2013
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Like other members of the ?-herpesvirus family, human herpes virus 8, the etiologic agent of classic and HIV-related Kaposis sarcoma (HIV-KS) acquired and evolved several human genes with key immune modulatory and cellular growth control functions. The encoded viral homologs substitute for their human counterparts but escape cellular regulation, leading to uncontrolled cell proliferation. We postulated that DNA variants in the human homologs of viral genes that potentially alter the expression or the binding of the encoded factors controlling the antiviral response may facilitate viral interference. To test whether cellular homologs are candidate susceptibility genes, we evaluated the association of DNA variants in 92 immune-related genes including seven cellular homologs with the risk for HIV-KS in a matched case and control study nested in the Multicenter AIDS Cohort Study. Low- and high-risk gene-by-gene interactions were estimated by multifactor dimensionality reduction and used as predictors in conditional logistic models. Among the most significant gene interactions at risk (OR?=?2.84-3.92; Bonferroni- adjusted p?=?9.9 × 10(-3) - 2.6 × 10(-4) ), three comprised human homologs of two latently expressed viral genes, cyclin D1 (CCND1) and interleukin-6 (IL-6), in conjunction with angiogenic genes (VEGF, EDN-1 and EDNRB). At lower significance thresholds (adjusted p < 0.05), human homologs related to apoptosis (CFLAR) and chemotaxis (CCL2) emerged as candidates. This "proof of concept" study identified human homologs involved in the regulation of type I interferon-induced signaling, cell cycle and apoptosis potentially as important determinants of HIV-KS.
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Transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure.
PLoS Negl Trop Dis
PUBLISHED: 04-01-2013
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Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1? and IL23?, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response.
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Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development.
PLoS Negl Trop Dis
PUBLISHED: 04-01-2013
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Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC) exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirins failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential exposure routes and provides important insights into the development and evaluation of potential vaccines and therapeutics to treat RVFV infection.
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Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011.
Clin. Infect. Dis.
PUBLISHED: 03-26-2013
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Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)-infected and -uninfected men who have sex with men (MSM) over the entire HIV epidemic has not been comprehensively conducted.
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Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.
Clin. Infect. Dis.
PUBLISHED: 03-26-2013
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Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.
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Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-09-2013
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By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups.
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Serum proinflammatory cytokine responses to influenza virus vaccine among women during pregnancy versus non-pregnancy.
Am. J. Reprod. Immunol.
PUBLISHED: 02-05-2013
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This study aimed to comprehensively describe inflammatory responses to trivalent influenza virus vaccine (TIV) among pregnant women and determine whether responses differ compared to non-pregnancy.
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Use of cardiac CT angiography imaging in an epidemiology study - the Methodology of the Multicenter AIDS Cohort Study cardiovascular disease substudy.
Anadolu Kardiyol Derg
PUBLISHED: 01-30-2013
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The methodology for use of cardiac CT angiography (CTA) in low risk populations is not well defined. In order to present a reference for future studies, we present CTA methodology that is being used in an epidemiology study- the Multicenter AIDS Cohort Study (MACS).
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A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.
Hum. Mol. Genet.
PUBLISHED: 01-30-2013
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Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 ?32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 ?32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.