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1.
Infect Control Hosp Epidemiol ; 43(2): 199-204, 2022 02.
Article in English | MEDLINE | ID: mdl-33820578

ABSTRACT

OBJECTIVE: To determine whether cascade reporting is associated with a change in meropenem and fluoroquinolone consumption. DESIGN: A quasi-experimental study was conducted using an interrupted time series to compare antimicrobial consumption before and after the implementation of cascade reporting. SETTING: A 399-bed, tertiary-care, Veterans' Affairs medical center. PARTICIPANTS: Antimicrobial consumption data across 8 inpatient units were extracted from the Center for Disease Control and Prevention (CDC) National Health Safety Network (NHSN) antimicrobial use (AU) module from April 2017 through March 2019, reported as antimicrobial days of therapy (DOT) per 1,000 days present (DP). INTERVENTION: Cascade reporting is a strategy of reporting antimicrobial susceptibility test results in which secondary agents are only reported if an organism is resistant to primary, narrow-spectrum agents. A multidisciplinary team developed cascade reporting algorithms for gram-negative bacteria based on local antibiogram and infectious diseases practice guidelines, aimed at restricting the use of fluoroquinolones and carbapenems. The algorithms were implemented in March 2018. RESULTS: Following the implementation of cascade reporting, mean monthly meropenem (P =.005) and piperacillin/tazobactam (P = .002) consumption decreased and cefepime consumption increased (P < .001). Ciprofloxacin consumption decreased by 2.16 DOT per 1,000 DP per month (SE, 0.25; P < .001). Clostridioides difficile rates did not significantly change. CONCLUSION: Ciprofloxacin consumption significantly decreased after the implementation of cascade reporting. Mean meropenem consumption decreased after cascade reporting was implemented, but we observed no significant change in the slope of consumption. cascade reporting may be a useful strategy to optimize antimicrobial prescribing.


Subject(s)
Anti-Infective Agents , Veterans , Anti-Bacterial Agents/therapeutic use , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Gram-Negative Bacteria , Humans , Meropenem/therapeutic use , Microbial Sensitivity Tests
2.
BMC Public Health ; 21(1): 1399, 2021 07 15.
Article in English | MEDLINE | ID: mdl-34266390

ABSTRACT

BACKGROUND: Epidemiological surveillance data indicate that a majority of HIV-infected in the United States (U.S.) military are African-Americans and men who have sex with men. There is limited research about barriers to HIV prevention among military service members and the unique factors that contribute to HIV stigma. METHODS: A convenience sample of 30 U.S. service members were recruited from an infectious disease clinic. In depth interviews were conducted and data analyzed using a thematic coding process. RESULTS: Two broad categories were identified: 1) Outcomes of HIV Stigma: Fear of Rejection, Shame, and Embarrassment; and 2) Strategies for combating stigma which include increasing HIV education and prevention resources. Military policies and institutional culture regarding sexuality were found to contribute to stigma. CONCLUSIONS: Participants identified a need for HIV education and suggested individuals living with HIV serve as mentors. A peer-to-peer intervention for delivering HIV prevention education may address these needs and reduce HIV stigma.


Subject(s)
HIV Infections , Military Personnel , Sexual and Gender Minorities , Homosexuality, Male , Humans , Male , Social Stigma , United States/epidemiology
3.
Sci Data ; 7(1): 277, 2020 09 08.
Article in English | MEDLINE | ID: mdl-32901023

ABSTRACT

Biological invasions are responsible for tremendous impacts globally, including huge economic losses and management expenditures. Efficiently mitigating this major driver of global change requires the improvement of public awareness and policy regarding its substantial impacts on our socio-ecosystems. One option to contribute to this overall objective is to inform people on the economic costs linked to these impacts; however, until now, a reliable synthesis of invasion costs has never been produced at a global scale. Here, we introduce InvaCost as the most up-to-date, comprehensive, harmonised and robust compilation and description of economic cost estimates associated with biological invasions worldwide. We have developed a systematic, standardised methodology to collect information from peer-reviewed articles and grey literature, while ensuring data validity and method repeatability for further transparent inputs. Our manuscript presents the methodology and tools used to build and populate this living and publicly available database. InvaCost provides an essential basis (2419 cost estimates currently compiled) for worldwide research, management efforts and, ultimately, for data-driven and evidence-based policymaking.


Subject(s)
Ecosystem , Introduced Species/economics , Databases as Topic
4.
Anal Chem ; 91(21): 13703-13711, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31600444

ABSTRACT

Imaging the inventory of microbial small molecule interactions provides important insights into microbial chemical ecology and human medicine. Herein we demonstrate a new method for enhanced detection and analysis of metabolites present in interspecies interactions of microorganisms on surfaces. We demonstrate that desorption electrospray ionization-imaging mass spectrometry (DESI-IMS) using microporous membrane scaffolds (MMS) enables enhanced spatiochemical analyses of interacting microbes among tested sample preparation techniques. Membrane scaffolded DESI-IMS has inherent advantages compared to matrix-assisted laser desorption ionization (MALDI) and other IMS methods through direct IMS analyses of microbial chemistry in situ. This rapid imaging method yields sensitive MS analyses with unique m/z measurements when compared to liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) via unmediated sampling by MMS DESI-IMS. Unsupervised segmentation imaging analysis of acquired DESI-IMS data reveals distinct chemical regions corresponding to intermicrobial phenomenon such as predation and communication. We validate the method by linking Myxovirescin A and DKxanthene-560 to their known biological roles of predation and phase variation, respectively. In addition to providing the first topographic locations of known natural products, we prioritize 54 unknown features using segmentation within the region of predation. Thus, DESI-IMS and unsupervised segmentation spatially annotates the known biology of myxobacteria and provides functional exploration of newly uncharacterized small molecules.


Subject(s)
Ion Mobility Spectrometry/methods , Membranes, Artificial , Microbial Interactions , Spectrometry, Mass, Electrospray Ionization/methods
5.
J Fr Ophtalmol ; 41(10): 939-944, 2018 Dec.
Article in French | MEDLINE | ID: mdl-30442489

ABSTRACT

PURPOSE: To evaluate the anatomical and functional outcomes of macular hole (MH) surgery with a temporal inverted internal limiting membrane (ILM) flap technique. METHODS: Monocentric retrospective study of 24 patients who were operated on for macular hole between March 2014 and April 2017 at Nancy University Hospital. All patients underwent pars plana vitrectomy with the inverted ILM flap technique. ILM peeling was restricted to the temporal side of the fovea, and the macular hole was then covered with the ILM flap, followed by SF6 tamponnade and first day face-down positioning. The main outcome measures included macular hole closure rate and visual acuity at 1 month postoperatively. RESULTS: Eight men and 16 women of mean age 67.0±5.4 years were included. The mean axial length was 23.5±1.2mm. The mean diameter of the MH was 362±123µm. Closure of the MH was achieved in 23 of 24 eyes (95.8%) after one surgery. The mean BVCA improved significantly from 0.71±0.20 logMar to 0.29±0.22 logMar (P<0.001) at 1 month postoperatively, for a gain of 0.42±0.24 logMar. CONCLUSION: Macular hole surgery with the inverted ILM flap technique results in good anatomical and functional outcomes, comparable to those obtained with the classic technique with complete ILM peeling.


Subject(s)
Retinal Perforations/pathology , Retinal Perforations/surgery , Surgical Flaps/transplantation , Vitrectomy/methods , Vitrectomy/rehabilitation , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/pathology , Retinal Perforations/physiopathology , Retrospective Studies , Vitrectomy/adverse effects
6.
Am J Public Health ; 108(10): 1345-1348, 2018 10.
Article in English | MEDLINE | ID: mdl-30138058

ABSTRACT

It was the summer of 1972 when a stunned nation first learned of the infamous Tuskegee Syphilis Study, during which hundreds of poor, disease-stricken black men from Macon County Alabama, had been deliberately left untreated for 40 years. Coming on the heels of multiple, earlier examples of unethical human experimentation, the Tuskegee Syphilis Study made it plain that the moral foundation of human subject research was in desperate need of repair. Blind reliance on the Nuremberg Code and the Declaration of Helsinki was no longer going to suffice. It was against this backdrop that Congress resolved to act. Numerous hearings and multiple spirited discussions later, an agreement was struck to constitute the "Commission." The outgrowth of a retreat held at the Smithsonian Institution's Belmont Conference Center, the Belmont Report lays out a principled analytical framework to "guide the resolution of ethical problems arising from research involving human subjects." Durable and ever-present, the Belmont Report, which is the foundational document that reset the ethics of human subject research, must now reckon with all-important novel issues of the day that could not have been foreseen by its drafters.


Subject(s)
Biomedical Research/ethics , Ethics, Research , Human Experimentation/ethics , Social Justice/ethics , Black or African American , Alabama , Female , Humans , Informed Consent/ethics , Male , Patient Selection/ethics , Personal Autonomy , Research Subjects , Syphilis/epidemiology , United States , Volunteers
7.
J Genet Couns ; 27(1): 16-20, 2018 02.
Article in English | MEDLINE | ID: mdl-29052810

ABSTRACT

As of May 2017, there were 4242 Certified Genetic Counselors (CGC) (American Board of Genetic Counseling, Inc. 2017) and 41 graduate-level genetic counseling training programs (Accreditation Council for Genetic Counseling 2017) in North America, and the demand for CGCs continues to increase. In the Fall of 2015 the Genetic Counselor Workforce Working Group, comprised of representatives from the American Board of Genetic Counseling (ABGC), the Accreditation Council for Genetic Counseling (ACGC), the Association of Genetic Counseling Program Directors (AGCPD), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC) commissioned a formal workforce study to project supply of and demand for CGCs through 2026. The data indicate a shortage of genetic counselors engaged in direct patient care. Assuming two scenarios for demand, supply is expected to reach equilibrium between 2024 and 2030. However, given the rate of growth in genetic counseling training programs in the six months since the study was completed, it is reasonable to expect that the number of new programs may be higher than anticipated by 2026. If true, and assuming that growth in programs is matched by equivalent growth in clinical training slots, the supply of CGCs in direct patient care would meet demand earlier than these models predict.


Subject(s)
Allied Health Personnel/organization & administration , Certification , Counselors/organization & administration , Genetic Counseling/organization & administration , Professional Role , Accreditation , Counseling/organization & administration , Education, Graduate , Humans , United States
8.
J Clin Apher ; 32(6): 567-570, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27709659

ABSTRACT

HIV complicates the diagnostic and therapeutic approaches to idiopathic thrombotic thrombocytopenic purpura (TTP), prompting debate in the literature regarding the benefit of plasma exchange versus simple plasma infusion. Herein we present a case of HIV-TTP, initially treated conservatively with plasma infusion but because of progressive neurologic decline, required urgent plasma exchange for resolution of hematologic derangements and neurologic sequelae. Based on the available literature, there appears to be a spectrum of HIV-associated TTP disorders. Patients with advanced HIV disease and opportunistic infections who present with thrombotic microangiopathy tend to respond to simple plasma infusion, while patients with less progressive HIV disease tend to behave like those with idiopathic TTP, requiring plasma exchange rather than simple plasma infusion. This article illustrates that in patients with HIV-TTP who do not respond to plasma infusion, early escalation to plasma exchange may help avoid life-threatening complications such as seizures and even death.


Subject(s)
HIV Infections , Plasma Exchange/methods , Purpura, Thrombotic Thrombocytopenic/therapy , Purpura, Thrombotic Thrombocytopenic/virology , Adult , Female , Humans , Plasma , Purpura, Thrombotic Thrombocytopenic/complications
9.
Antiviral Res ; 137: 102-107, 2017 01.
Article in English | MEDLINE | ID: mdl-27871886

ABSTRACT

BACKGROUND: Benzimidazole D-ribonucleosides are potent and selective inhibitors of CMV infection that have been shown to target the viral terminase, the enzyme complex responsible for viral DNA cleavage into single unit-length genomes and subsequent DNA packaging into procapsids. Here, we evaluated the viral inhibition by benzimidazole D-ribonucleosides against rat cytomegalovirus (RCMV). METHODS: Antiviral activity of compounds Cl4RB and BTCRB against RCMV was quantified by measurement of plaque formation. Yield assays and electron microscopy of thin sections was performed using RCMV-infected cells in the presence or absence of the compounds. The effects of Cl4RB and BTCRB on cleavage of concatemers was analyzed by pulsed-field gel electrophoresis. To characterize the behaviour of the antiviral compounds in a more physiological environment, a 3D cell culture model was employed where cells are embedded in an extracellular matrix using rat-tail collagen I. RESULTS: Both compounds had an inhibitory effect against RCMV-E. Electron microscopy revealed that only few virions were formed in RCMV-E infected cells in the presence of the compounds. Pulsed-field gel electrophoresis showed that DNA concatemers failed to be processed in the presence of the compounds. Yield Assays showed a comparable viral growth in the 3D vs. 2D cell culture as well as inhibition in the presence of Cl4RB or BTCRB for RCMV-E/GFP. CONCLUSIONS: These results demonstrate that the tetrahalogenated benzimidazole D-ribonucleosides are effective against RCMV-E by preventing cleavage of concatemeric DNA and nuclear egress of mature capsids.


Subject(s)
Antiviral Agents/pharmacology , Benzimidazoles/pharmacology , Herpesviridae Infections/drug therapy , Muromegalovirus/drug effects , Nucleosides/pharmacology , Ribonucleosides/pharmacology , Animals , Antiviral Agents/chemistry , Benzimidazoles/chemistry , Cell Culture Techniques , Collagen/chemistry , DNA Packaging/drug effects , Endodeoxyribonucleases/drug effects , Halogenation , Herpesviridae Infections/virology , Microscopy, Electron , Models, Biological , Muromegalovirus/ultrastructure , Nucleosides/chemistry , Rats , Ribonucleosides/chemistry , Tissue Scaffolds , Viral Plaque Assay
10.
J Genet Couns ; 26(3): 640-655, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27858211

ABSTRACT

Fanconi anemia (FA) is characterized by congenital malformations, progressive bone marrow failure, and predisposition to malignancy. Hematopoietic stem cell transplantation is used to treat FA, and best results are attained with sibling donors who are human leukocyte antigen (HLA) identical matches. Preimplantation genetic diagnosis (PGD) offers parents of an affected child the opportunity to have an unaffected child who is an HLA match. While some research has investigated parents' experiences during the PGD process, no published studies specifically address factors influencing their decision-making process and long-term interpersonal outcomes. The aims of this study are to: (1) examine parents' expectations and the influence of media, bioethics, and religion on their decision to undergo PGD; (2) examine parents' social support and emotional experiences during their PGD process; and (3) characterize long-term effects of PGD on relationship dynamics (partner, family, friends), others' attitudes, and parental regret. Nine parents participated in semi-structured interviews. Thematic analysis revealed their decision to use PGD was variously influenced by media, bioethics, and religion, in particular, affecting parents' initial confidence levels. Moreover, the PGD process was emotionally complex, with parents desiring varying amounts and types of support from different sources at different times. Parents reported others' attitudes towards them were similar or no different than before PGD. Parental regret regarding PGD was negligible. Results of this study will promote optimization of long-term care for FA families.


Subject(s)
Decision Making , Fanconi Anemia/diagnosis , Fanconi Anemia/genetics , Parents , Preimplantation Diagnosis , Adult , Female , Humans , Male , Parents/psychology , Pregnancy , Preimplantation Diagnosis/psychology , Qualitative Research
11.
Proteomics ; 16(15-16): 2284-301, 2016 08.
Article in English | MEDLINE | ID: mdl-27296928

ABSTRACT

In proteomics studies, it is generally accepted that depth of coverage and dynamic range is limited in data-directed acquisitions. The serial nature of the method limits both sensitivity and the number of precursor ions that can be sampled. To that end, a number of data-independent acquisition (DIA) strategies have been introduced with these methods, for the most part, immune to the sampling issue; nevertheless, some do have other limitations with respect to sensitivity. The major limitation with DIA approaches is interference, i.e., MS/MS spectra are highly chimeric and often incapable of being identified using conventional database search engines. Utilizing each available dimension of separation prior to ion detection, we present a new multi-mode acquisition (MMA) strategy multiplexing both narrowband and wideband DIA acquisitions in a single analytical workflow. The iterative nature of the MMA workflow limits the adverse effects of interference with minimal loss in sensitivity. Qualitative identification can be performed by selected ion chromatograms or conventional database search strategies.


Subject(s)
Proteomics/methods , Tandem Mass Spectrometry/methods , Software
12.
J Vet Intern Med ; 30(1): 200-5, 2016.
Article in English | MEDLINE | ID: mdl-26725776

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. OBJECTIVES/HYPOTHESIS: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. ANIMALS: Five purpose-bred dogs. METHODS: Prospective study. Acute kidney injury, defined as a > 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. RESULTS: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50% increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P = .009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). CONCLUSIONS AND CLINICAL IMPORTANCE: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.


Subject(s)
Acute Kidney Injury/veterinary , Acute-Phase Proteins/metabolism , Dog Diseases/chemically induced , Lipocalins/metabolism , Proto-Oncogene Proteins/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/urine , Acute-Phase Proteins/genetics , Acute-Phase Proteins/urine , Animals , Creatinine/urine , Dog Diseases/blood , Dog Diseases/metabolism , Dogs , Lipocalins/genetics , Lipocalins/urine , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/urine
13.
Vet Pathol ; 53(1): 211-21, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26123229

ABSTRACT

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases.


Subject(s)
Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , MicroRNAs/blood , Rats, Sprague-Dawley , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Biomarkers/blood , Glutamate Dehydrogenase/blood , Liver/pathology , Male , Rats , Toxicology
14.
Microbiology (Reading) ; 161(Pt 5): 1061-1072, 2015 May.
Article in English | MEDLINE | ID: mdl-25737481

ABSTRACT

Purple non-sulfur bacteria are well known for their metabolic versatility. One of these bacteria, Rhodospirillum rubrum S1H, has been selected by the European Space Agency to ensure the photoheterotrophic assimilation of volatile fatty acids in its regenerative life support system, MELiSSA. Here, we combined proteomic analysis with bacterial growth analysis and enzymatic activity assays in order to better understand acetate photoassimilation. In this isocitrate lyase-lacking organism, the assimilation of two-carbon compounds cannot occur through the glyoxylate shunt, and the citramalate cycle has been proposed to fill this role, while, in Rhodobacter sphaeroides, the ethylmalonyl-CoA pathway is used for acetate assimilation. Using proteomic analysis, we were able to identify and quantify more than 1700 unique proteins, representing almost one-half of the theoretical proteome of the strain. Our data reveal that a pyruvate : ferredoxin oxidoreductase (NifJ) could be used for the direct assimilation of acetyl-CoA through pyruvate, potentially representing a new redox-balancing reaction. We additionally propose that the ethylmalonyl-CoA pathway could also be involved in acetate assimilation by the examined strain, since specific enzymes of this pathway were all upregulated and activity of crotonyl-CoA reductase/carboxylase was increased in acetate conditions. Surprisingly, we also observed marked upregulation of glutaryl-CoA dehydrogenase, which could be a component of a new pathway for acetate photoassimilation. Finally, our data suggest that citramalate could be an intermediate of the branched-chain amino acid biosynthesis pathway, which is activated during acetate assimilation, rather than a metabolite of the so-called citramalate cycle.


Subject(s)
Acetates/metabolism , Light , Rhodospirillum rubrum/physiology , Acyl Coenzyme A/metabolism , Biological Transport , Carbon/metabolism , Fatty Acids/metabolism , Glutaryl-CoA Dehydrogenase/metabolism , Malates/metabolism , Metabolic Networks and Pathways , Oxidation-Reduction , Proteomics
15.
Antimicrob Agents Chemother ; 59(1): 226-32, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25348532

ABSTRACT

Human cytomegalovirus (HCMV) infection can cause severe illnesses, including encephalopathy and mental retardation, in immunocompromised and immunologically immature patients. Current pharmacotherapies for treating systemic HCMV infections include ganciclovir, cidofovir, and foscarnet. However, long-term administration of these agents can result in serious adverse effects (myelosuppression and/or nephrotoxicity) and the development of viral strains with reduced susceptibility to drugs. The deoxyribosylindole (indole) nucleosides demonstrate a 20-fold greater activity in vitro (the drug concentration at which 50% of the number of plaques was reduced with the presence of drug compared to the number in the absence of drug [EC50] = 0.34 µM) than ganciclovir (EC50 = 7.4 µM) without any observed increase in cytotoxicity. Based on structural similarity to the benzimidazole nucleosides, we hypothesize that the indole nucleosides target the HCMV terminase, an enzyme responsible for packaging viral DNA into capsids and cleaving the DNA into genome-length units. To test this hypothesis, an indole nucleoside-resistant HCMV strain was isolated, the open reading frames of the genes that encode the viral terminase were sequenced, and a G766C mutation in exon 1 of UL89 was identified; this mutation resulted in an E256Q change in the amino acid sequence of the corresponding protein. An HCMV wild-type strain, engineered with this mutation to confirm resistance, demonstrated an 18-fold decrease in susceptibility to the indole nucleosides (EC50 = 3.1 ± 0.7 µM) compared to that of wild-type virus (EC50 = 0.17 ± 0.04 µM). Interestingly, this mutation did not confer resistance to the benzimidazole nucleosides (EC50 for wild-type HCMV = 0.25 ± 0.04 µM, EC50 for HCMV pUL89 E256Q = 0.23 ± 0.04 µM). We conclude, therefore, that the G766C mutation that results in the E256Q substitution is unique for indole nucleoside resistance and distinct from previously discovered substitutions that confer both indole and benzimidazole nucleoside resistance (D344E and A355T).


Subject(s)
Benzimidazoles/pharmacology , Cytomegalovirus/drug effects , Deoxyribonucleosides/pharmacology , Drug Resistance, Viral/genetics , Indoles/pharmacology , Ribonucleosides/pharmacology , Viral Proteins/genetics , Amino Acid Sequence , Antiviral Agents/pharmacology , Base Sequence , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Molecular Sequence Data , Mutation
16.
J Phys Condens Matter ; 26(30): 303201, 2014 Jul 30.
Article in English | MEDLINE | ID: mdl-24994551

ABSTRACT

The field of graphene research has developed rapidly since its first isolation by mechanical exfoliation in 2004. Due to the relativistic Dirac nature of its charge carriers, graphene is both a promising material for next-generation electronic devices and a convenient low-energy testbed for intrinsically high-energy physical phenomena. Both of these research branches require the facile fabrication of clean graphene devices so as not to obscure its intrinsic physical properties. Hexagonal boron nitride has emerged as a promising substrate for graphene devices as it is insulating, atomically flat and provides a clean charge environment for the graphene. Additionally, the interaction between graphene and boron nitride provides a path for the study of new physical phenomena not present in bare graphene devices. This review focuses on recent advancements in the study of graphene on hexagonal boron nitride devices from the perspective of scanning tunneling microscopy with highlights of some important results from electrical transport measurements.

18.
J Phys Condens Matter ; 25(50): 505304, 2013 Dec 18.
Article in English | MEDLINE | ID: mdl-24275340

ABSTRACT

Raman spectroscopy, a fast and nondestructive imaging method, can be used to monitor the doping level in graphene devices. We fabricated chemical vapor deposition (CVD) grown graphene on atomically flat hexagonal boron nitride (hBN) flakes and SiO2 substrates. We compared their Raman response as a function of charge carrier density using an ion gel as a top gate. The G peak position, the 2D peak position, the 2D peak width and the ratio of the 2D peak area to the G peak area show a dependence on carrier density that differs for hBN compared to SiO2. Histograms of two-dimensional mapping are used to compare the fluctuations in the Raman peak properties between the two substrates. The hBN substrate has been found to produce fewer fluctuations at the same charge density owing to its atomically flat surface and reduced charged impurities.


Subject(s)
Boron Compounds/chemistry , Graphite/chemistry , Nanostructures/chemistry , Silicon Dioxide/chemistry , Spectrum Analysis, Raman , Crystallization , Materials Testing , Surface Properties
19.
J Vet Intern Med ; 27(6): 1362-7, 2013.
Article in English | MEDLINE | ID: mdl-24020513

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a common and often fatal disorder in dogs. HYPOTHESIS: Urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine ratio is a sensitive and specific biomarker of AKI in dogs. ANIMALS: Ninety-four dogs. METHODS: Prospective study. Dogs were classified as follows: (1) healthy dogs, (2) dogs with lower urinary tract disorders, (3) dogs with chronic kidney disease (CKD), (4) dogs with azotemic International Renal Interest Society (IRIS) AKI Grades II-V, and (5) dogs with IRIS AKI Grade I (nonazotemic). Urinary NGAL was quantitated in each dog using an ELISA assay and concentrations were expressed as a ratio to urinary creatinine concentration from the same specimen, and designated the urinary NGAL/creatinine ratio (UNCR). RESULTS: There was a significant difference in UNCR among the study groups (P < .001). Both the azotemic and nonazotemic AKI groups had higher UNCR when compared with all other groups (P < .001 for all pairs). There was a statistically significant difference in UNCR between dogs diagnosed with CKD compared with dogs with lower urinary tract diseases (P = .005) as well as between dogs with CKD and healthy dogs (P = .001). Receiver operator characteristics (ROC) analysis of UNCR as an indicator of azotemic and nonazotemic AKI had an area under the ROC curve of 0.94 and 0.96, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: NGAL/creatinine ratio is a sensitive and specific marker of AKI. It can be used to screen patients at risk for AKI and can be utilized to diagnose milder forms of AKI potentially earlier in the course of the disease.


Subject(s)
Acute Kidney Injury/veterinary , Biomarkers/urine , Creatinine/urine , Dog Diseases/pathology , Lipocalins/urine , Acute Kidney Injury/pathology , Acute Kidney Injury/urine , Animals , Dog Diseases/urine , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Male , Predictive Value of Tests , Prospective Studies , ROC Curve , Sensitivity and Specificity
20.
Med Mal Infect ; 43(7): 295-8, 2013 Jul.
Article in French | MEDLINE | ID: mdl-23906420

ABSTRACT

OBJECTIVES: The authors had for aim to assess the inter- and intra-individual variability of teicoplanin pharmacokinetic parameters in geriatric patients. METHODS: A cohort of 90 geriatric patients, treated with teicoplanin, was used to build two models describing the pharmacokinetics of teicoplanin, at the beginning and at the end of treatment respectively. RESULTS: The inter- and intra-individual variability of parameters were important as shown respectively by the coefficients of variation of pharmacokinetic parameters ranging from 125 to 694% and the half-life change during the treatment (by a factor of three to more than 30) for 60% of patients. CONCLUSIONS: The results revealed that elderly patients presented significant variability, which was only partly explained by the renal function. Therapeutic monitoring of teicoplanin in geriatric patients should be undertaken at the end of the loading dose and repeatedly during the maintenance phase to prevent over- or underexposure.


Subject(s)
Aging/metabolism , Anti-Bacterial Agents/pharmacokinetics , Teicoplanin/pharmacokinetics , Aged , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Drug Monitoring , Genetic Variation , Half-Life , Humans , Kidney/physiology , Models, Biological , Retrospective Studies , Teicoplanin/therapeutic use
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