bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic accuracy of Heidelberg Retina Tomograph III classifications in a Turkish primary open‐angle glaucoma population
Authors: Bozkurt Banu , Irkec Murat , Arslan Umut 
Published: July 2009

Abstract.Purpose:  This study aimed to evaluate the diagnostic accuracy of Moorfields regression analysis (MRA) and the glaucoma probability score (GPS) in primary open‐angle glaucoma (POAG) and to measure the level of agreement between the two algorithms in classifying eyes as normal or abnormal in a Turkish population.Methods:  We prospectively selected 184 healthy subjects and 158 subjects with POAG, who underwent an ophthalmological examination, visual field analysis and imaging with the Heidelberg Retina Tomograph II, using HRT III software, Version 3.0. The diagnostic accuracies of the two classifications were measured when the borderline was taken as either normal (highest specificity criteria) or abnormal (highest sensitivity criteria). The agreement between them was calculated using the unweighted kappa (κ) coefficient.Results:  Optic nerve head topographic parameters showed statistically significant differences between the control and POAG groups (p < 0.001). The parameters with the highest area under the receiver operating characteristic curves were global GPS (0.86), cup : disc area (0.85), rim : disc area (0.85) and vertical cup : disc (0.85). According to the highest specificity criteria, MRA had a sensitivity of 67.7% and a specificity of 95.1%, whereas the GPS had a sensitivity of 70.9% and a specificity of 88.0%. According to the highest sensitivity criteria, MRA had a sensitivity of 81.0% and a specificity of 75.0%, whereas the GPS had a sensitivity of 89.2% and a specificity of 57.6%. A moderate agreement of 68% (233 eyes) with a κ coefficient of 0.51 was found between MRA and the GPS.Conclusions:  The GPS automated classification showed similar sensitivity to MRA, but considerably lower specificity, when applied in a Turkish population.
Management of congenital nasolacrimal duct obstruction
Authors: Takahashi Yasuhiro , Kakizaki Hirohiko , Chan Weng O. , Selva Dinesh 
Published: July 2009

Abstract.Our review aims to provide an update of management protocols for congenital nasolacrimal duct obstruction (CNDO). Although early probing performed before the age of 1 year was traditionally recommended, many reports have since confirmed high frequencies of spontaneous resolution during the first year of life. Accordingly, a ‘wait‐and‐see’ approach, combined with conservative therapies, is judged to be the best option in infants aged < 1 year. By contrast, persistent obstruction beyond 1 year of age warrants probing as a first‐line interventional therapy. However, the optimal timing for probing remains controversial. Although there remains a high possibility of spontaneous resolution after the first year of age, this must be balanced against the decrease in success rates for probing that accompanies advancing age. If conservative management fails, persistent CNDO beyond 1 year of age should be managed either by further observation or by primary probing according to the severity of symptoms. In patients in whom probing fails, advanced treatment such as balloon catheter dilation, silicone tube intubation or dacryocystorhinostomy may be considered.
Analysis of clonally related environmental Vibrio cholerae O1 El Tor isolated before 1992 from Varanasi, India reveals origin of SXT‐ICEs belonging to O139 and O1 serogroups
Authors: Mohapatra Saswat S. , Mantri Chinmay K. , Mohapatra Harapriya , Colwell Rita R. , Singh Durg V. 
Published: July 2009

SummaryIn this study, we report the presence of SXT in environmental Vibrio cholerae O1 El Tor strains isolated before 1992 from Varanasi, India. All isolates, except one, were resistant to Tm, and/or Sul, Sm, Fr, Na and Am. None contained plasmids. PCR and DNA sequencing revealed the presence of SXT containing dfrA1 and/or sulII, strAB in six isolates and dfr18, sulII and strAB in five isolates. Three clinical V. cholerae O1 isolated during 1992 contained the antibiotic resistance gene cassette aadA1 in the class 1 integron. Conjugation experiments, followed by PCR analysis of transconjugants, provided evidence of the transferable nature of SXT and associated antibiotic resistance genes, and its integration into the prfC site. Results of phylogenetic analysis of the intSXT gene of clonally similar V. cholerae showed a clear difference between dfr18+ and dfrA1+V. cholerae O1 isolates. This is the first report of the occurrence of SXT harbouring sulII, strAB, dfr18 and/or dfrA1 genes in environmental V. cholerae O1 isolated prior to 1992 from Varanasi, India, and suggests emergence of SXT+ antibiotic‐resistant V. cholerae O139 and O1 from an environmental V. cholerae progenitor by acquisition of SXT and antibiotic‐resistant gene clusters.
Laparoscopic gastric surgery in Asia
Authors: Yang Han‐Kwang 
Published: July 2009

Abstract:Laparoscopic gastric surgery has been popular in Asia since 1991. Laparoscopic gastrectomies are widely performed in Korea and Japan because of high incidence of early gastric cancer. Short‐term and long‐term outcomes after laparoscopic surgery for gastric cancer were actively reported, but waiting for multicenter randomized controlled trial. Education including domestic training workshop and international collaboration promise to progress advanced laparoscopic gastric surgery with robot and augmented reality surgery.
Laparoscopic Colorectal Surgery in Asia
Authors: Li Michael , CHEUNG Hester Yui Shan , CHUNG Cliff Chi Chiu 
Published: July 2009

Abstract:Laparoscopic colorectal surgery in Asia has gone a long way since 1992. In this article, the authors attempted to unfold the history of laparoscopic colorectal surgery in Asia, and report on the latest development. It is concluded that laparoscopic colorectal surgery will continue to flourish in Asia, and we will be entering a new era of endo‐laparoscopic surgery and robotic assisted laparoscopic surgery.
Novel Genetic Environment of the Carbapenem-Hydrolyzing β-Lactamase KPC-2 among
Enterobacteriaceae
in China
Authors: Shen Ping , Wei Zeqing , Jiang Yan , Du Xiaoxing , Ji Shujuan , Yu Yunsong , Li Lanjuan 
Published: July 2009

ABSTRACT

Thirty-nine
bla
KPC
-producing isolates of the family
Enterobacteriaceae
with carbapenem resistance or reduced carbapenem susceptibility were obtained from inpatients from eight hospitals in six cities of three provinces in eastern China. The pulsed-field gel electrophoresis analysis of all 36
Klebsiella pneumoniae
isolates revealed six major patterns. The resistant plasmids of most isolates were successfully transferred by conjugation and evaluated experimentally to be 40 to 180 kb in size. A 20.2-kb
bla
KPC
-surrounding nucleotide sequence from plasmid pKP048 has been obtained and contains an integration structure of a Tn
3
-based transposon and partial Tn
4401
segment, with the gene order Tn
3
-transposase, Tn
3
-resolvase, IS
Kpn8
, the
bla
KPC-2
gene, and the IS
Kpn6
-like element. The chimera of several transposon-associated elements indicated a novel genetic environment of the
K. pneumoniae
carbapenemase β-lactamase gene in isolates from China.
Pharmacokinetic Properties of Sulfadoxine-Pyrimethamine in Pregnant Women
Authors: Karunajeewa Harin A. , Salman Sam , Mueller Ivo , Baiwog Francisca , Gomorrai Servina , Law Irwin , Page-Sharp Madhu , Rogerson Stephen , Siba Peter , Ilett Kenneth F. , Davis Timothy M. E. 
Published: July 2009

ABSTRACT

To determine the pharmacokinetic disposition of sulfadoxine (SDOX) and pyrimethamine (PYR) when administered as intermittent presumptive treatment during pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were given a single dose of 1,500 mg of SDOX plus 75 mg of pyrimethamine PYR. Blood was taken at baseline and 1, 2, 4, 6, 12, 18, 24, 30, 48, and 72 h and at 7, 10, 14, 28, and 42 days posttreatment in all women. Plasma samples were assayed for SDOX,
N
-acetylsulfadoxine (NASDOX), and PYR by high-performance liquid chromatography. Population pharmacokinetic modeling was performed using NONMEM v6.2.0. Separate user-defined mamillary models were fitted to SDOX/NASDOX and PYR. When the covariate pregnancy was applied to clearance, there was a significant improvement in the base model for both treatments. Pregnancy was associated with a significantly lower area under the concentration-time curve from 0 to ∞ for SDOX (22,315 versus 33,284 mg·h/liter), NASDOX (801 versus 1,590 mg·h/liter), and PYR (72,115 versus 106,065 μg·h/liter;
P
< 0.001 in each case). Because lower plasma concentrations of SDOX and PYR could compromise both curative efficacy and posttreatment prophylaxis in pregnant patients, IPTp regimens incorporating higher mg/kg doses than those recommended for nonpregnant patients should be considered.
Imidocarb Dipropionate Clears PersistentBabesia caballiInfection with Elimination of Transmission Potential
Authors: Schwint O. Nicolas , Ueti Massaro W. , Palmer Guy H. , Kappmeyer Lowell S. , Hines Melissa T. , Cordes R. Timothy , Knowles Donald P. , Scoles Glen A. 
Published: July 2009

ABSTRACTAntimicrobial treatment of persistent infection to eliminate transmission risk represents a specific challenge requiring compelling evidence of complete pathogen clearance. The limited repertoire of antimicrobial agents targeted at protozoal parasites magnifies this challenge. UsingBabesia caballias both a model and a specific apicomplexan pathogen for which evidence of the elimination of transmission risk is required for international animal movement, we tested whether a high-dose regimen of imidocarb dipropionate cleared infection from persistently infected asymptomatic horses and/or eliminated transmission risk. Clearance with elimination of transmission risk was supported by the following four specific lines of evidence: (i) inability to detect parasites by quantitative PCR and nested PCR amplification, (ii) conversion from seropositive to seronegative status, (iii) inability to transmit infection by direct inoculation of blood into susceptible recipient horses, and (iv) inability to transmit infection by ticks acquisition fed on the treated horses and subsequently transmission fed on susceptible horses. In contrast, untreated horses remained infected and capable of transmittingB. caballiusing the same criteria. These findings establish that imidocarb dipropionate treatment clearsB. caballiinfection with confirmation of lack of transmission risk either by direct blood transfer or a high tick burden. Importantly, the treated horses revert to seronegative status according to the international standard for serologic testing and would be permitted to move between countries where the pathogen is endemic and countries that are free of the pathogen.
Pharmacokinetic Assessment of Nevirapine and Metabolites in Human Immunodeficiency Virus Type 1-Infected Patients with Hepatic Fibrosis
Authors: Cammett Anna Maria , MacGregor Thomas R. , Wruck Jan M. , Felizarta Franco , Miailhes Patrick , Mallolas Josep , Piliero Peter J. 
Published: July 2009

ABSTRACTNevirapine is a nonnucleoside reverse transcriptase inhibitor used as part of combination therapy for human immunodeficiency virus (HIV) infection. Nevirapine may be prescribed for patients with hepatic fibrosis and cirrhosis. Significant autoinduction of cytochrome P450 3A4 and 2B6 following multiple dosing prompted an assessment of the metabolic profiles in patients with liver disease receiving chronic nevirapine therapy. HIV-infected patients with hepatic fibrosis who were receiving a stable antiretroviral regimen containing nevirapine for ≥6 weeks had liver biopsy specimens assessed by Ishak histologic scoring and were grouped by severity (group 1, Ishak scores of 1 and 2; group 2, Ishak scores of 3 and 4; group 3, Ishak scores of 5 and 6). Steady-state trough nevirapine levels were determined for all patients, and additional measurements were obtained at 1, 2, and 4 h following nevirapine dosing for a subset of patients. The pharmacokinetics of nevirapine and its five metabolites were characterized, and a comparison of the results for the different Ishak groups was performed. Among 51 patients with hepatic fibrosis, the majority of whom were coinfected with hepatitis C virus or hepatitis B virus, differences between the maximum and the minimum observed plasma concentrations demonstrated a statistically significant flattening of the systemic exposure curves with progression from Ishak group 1 to Ishak group 2 or 3, suggesting a decrease in systemic clearance with the progression of liver disease. However, there were no significant differences in the trough and the maximum nevirapine concentrations between the Ishak groups. The metabolite profiles were also comparable across the Ishak groups. In HIV-infected patients who were chronically treated with nevirapine and who had various degrees of hepatic fibrosis, including cirrhosis, trough plasma nevirapine concentrations were not significantly increased, and thus, no dose adjustment is warranted.
Development of a Cell-Based Hepatitis C Virus Infection Fluorescent Resonance Energy Transfer Assay for High-Throughput Antiviral Compound Screening
Authors: Yu Xuemei , Sainz Bruno , Uprichard Susan L. 
Published: July 2009

ABSTRACT

A major obstacle in the treatment of chronic hepatitis C virus (HCV) infection has been the lack of effective, well-tolerated therapeutics. Notably, the recent development of the HCV cell culture infection system now allows not only for the study of the entire viral life cycle, but also for the screening of inhibitors against all aspects of HCV infection. However, in order to screen libraries of potential antiviral compounds, it is necessary to develop a highly reproducible, accurate assay for HCV infection adaptable for high-throughput screening (HTS) automation. Using an internally quenched 5-FAM/QXL 520 fluorescence resonance energy transfer (FRET) substrate containing the HCV NS3 peptide cleavage sequence, we report the development of a simple, mix-and-measure, homogenous, cell-based HCV infection assay amendable for HTS. This assay makes use of synchronized, nondividing human hepatoma-derived Huh7 cells, which support more-reproducible long-term HCV infection and can be readily scaled down to a 96-well-plate format. We demonstrate that this stable cell culture method eliminates common problems associated with standard cell-based HTS, such as cell culture variability, poor reproducibility, and low signal intensity. Importantly, this HCV FRET assay not only can identify inhibitors that act throughout the viral life cycle as effectively as more-standard HCV assays, such as real-time quantitative PCR and Western blot analysis, but also exhibits a high degree of accuracy with limited signal variation (i.e.,
Z
′ ≥ 0.6), providing the basis for a robust HTS campaign for screening compound libraries and identifying novel HCV antivirals.
In Vitro Antibacterial Activity of Acyl-Lysyl Oligomers againstHelicobacter pylori
Authors: Makobongo Morris O. , Kovachi Tchelet , Gancz Hanan , Mor Amram , Merrell D. Scott 
Published: July 2009

ABSTRACTThe gastric pathogenHelicobacter pylorihas developed resistance to virtually all current antibiotics; thus, there is a pressing need to develop new anti-H. pyloritherapies. The goal of this work was to evaluate the antibacterial effect of oligo-acyl-lysyl (OAK) antimicrobial peptidomimetics to determine if they might represent alternatives to conventional antibiotic treatment ofH. pyloriinfection. A total of five OAK sequences were screened for growth-inhibitory and/or bactericidal effects againstH. pyloristrain G27; four of these sequences had growth-inhibitory and bactericidal effects. The peptide with the highest efficacy against strain G27, C12K-2β12, was selected for further characterization against five additionalH. pyloristrains (26695, J99, 7.13, SS1, and HPAG1). C12K-2β12displayed MIC and minimum bactericidal concentration (MBC) ranges of 6.5 to 26 μM and 14.5 to 90 μM, respectively, across the six strains after 24 h of exposure. G27 was the most sensitiveH. pyloristrain (MIC = 6.5 to 7 μM; MBC = 15 to 20 μM), whereas 26695 was the least susceptible strain (MIC = 25 to 26 μM; MBC = 70 to 90 μM).H. pyloriwas completely killed after 6 to 8 h of incubation in liquid cultures containing two times the MBC of C12K-2β12. The OAK demonstrated strong in vitro stability, since efficacy was maintained after incubation at extreme temperatures (4°C, 37°C, 42°C, 50°C, 55°C, 60°C, and 95°C) and at low pH, although reduced killing kinetics were observed at pH 4.5. Additionally, upon transient exposure to the bacteria, C12K-2β12showed irreversible and significant antibacterial effects and was also nonhemolytic. Our results show a significant in vitro effect of C12K-2β12againstH. pyloriand suggest that OAKs may be a valuable resource for the treatment ofH. pyloriinfection.
Investigation of New Dominant-Negative Inhibitors of Anthrax Protective Antigen Mutants for Use in Therapy and Vaccination
Authors: Cao Sha , Guo Aizhen , Liu Ziduo , Tan Yadi , Wu Gaobing , Zhang Chengcai , Zhao Yaxing , Chen Huanchun 
Published: July 2009

ABSTRACT

The lethal toxin (LeTx) of
Bacillus anthracis
plays a key role in the pathogenesis of anthrax. The protective antigen (PA) is a primary part of the anthrax toxin and forms LeTx by combination with lethal factor (LF). Phenylalanine-427 (F427) is crucial for PA function. This study was designed to discover potential novel therapeutic agents and vaccines for anthrax. This was done by screening PA mutants that were mutated at the F427 residue for a dominant-negative inhibitory (DNI) phenotype which was nontoxic but inhibited the toxicity of the wild-type LeTx. For this, PA residue F427 was first mutated to each of the other 19 naturally occurring amino acids. The cytotoxicity and DNI phenotypes of the mutated PA proteins were tested in the presence of 1 μg/ml LF in RAW264.7 cells and were shown to be dependent on the individual amino acid replacements. A total of 16 nontoxic mutants with various levels of DNI activity were identified in vitro. Among them, F427D and F427N mutants had the highest DNI activities in RAW264.7 cells. Both mutants inhibited LeTx intoxication in mice in a dose-dependent way. Furthermore, they induced a Th2-predominant immune response and protected mice against a challenge with five 50% lethal doses of LeTx. The protection was correlated mainly with a low level of interleukin-1β (IL-1β) and with high levels of PA-specific immunoglobulin G1, IL-6, and tumor necrosis factor alpha. Thus, PA DNI mutants, such as F427D and F427N mutants, may serve in the development of novel therapeutic agents and vaccines to fight
B. anthracis
infections.
Indoleamine 2,3-Dioxygenase Is Involved in Defense againstNeospora caninumin Human and Bovine Cells
Authors: Spekker Katrin , Czesla Markus , Ince Vanessa , Heseler Kathrin , Schmidt Silvia K. , Schares Gereon , Däubener Walter 
Published: July 2009

ABSTRACTNeospora caninumis an apicomplexan parasite closely related toToxoplasma gondii. In nature this parasite is found especially in dogs and cattle, but it may also infect other livestock. The growth ofN. caninum, which is an obligate intracellular parasite, is controlled mainly by the cell-mediated immune response. During infection the cytokine gamma interferon (IFN-γ) plays a prominent role in regulating the growth ofN. caninumin natural and experimental disease. The present study showed that induction of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) is responsible for the inhibition of parasite growth that is mediated by IFN-γ-activated bovine fibroblasts and endothelial cells. This antiparasite effect could be abrogated by addition of tryptophan, as well as by the IDO-specific inhibitor 1-l-methyltryptophan. In conclusion, our data show that human and bovine cells use the same effector mechanism to control the growth ofN. caninum.
Comparative Analysis of the Properties and Ligand Binding Characteristics of CspZ, a Factor H Binding Protein, Derived fromBorrelia burgdorferiIsolates of Human Origin
Authors: Rogers Elizabeth A. , Abdunnur Shane V. , McDowell John V. , Marconi Richard T. 
Published: July 2009

ABSTRACTBorrelia burgdorferiCspZ (BBH06/BbCRASP-2) binds the complement regulatory protein factor H (FH) and additional unidentified serum proteins. The goals of this study were to assess the ligand binding capability of CspZ orthologs derived from an extensive panel of human Lyme disease isolates and to further define the molecular basis of the interaction between FH and CspZ. While mostB. burgdorferiCspZ orthologs analyzed bound FH, specific, naturally occurring polymorphisms, most of which clustered in a specific loop domain of CspZ, prevented FH binding in some orthologs. Sequence analyses also revealed the existence of CspZ phyletic groups that correlate with FH binding and with the relationships inferred from ribosomal spacer types (RSTs). CspZ type 1 (RST1) and type 3 (RST3) strains bind FH, while CspZ type 2 (RST2) strains do not. Antibody responses to CspZ were also assessed. Anti-CspZ antibodies were detected in mice by week 2 of infection, indicating that there was expression during early-stage infection. Analyses of sera collected from infected mice suggested that CspZ production continued over the course of long-term infection as the antibody titer increased over time. While antibody to CspZ was detected in several human Lyme disease serum samples, the response was not universal, and the titers were generally low. Vaccination studies with mice demonstrated that while CspZ is immunogenic, it does not elicit an antibody that is protective or that inhibits dissemination. The data presented here provide significant new insight into the interaction between CspZ and FH and suggest that there is a correlation between CspZ production and dissemination. However, in spite of its possible contributory role in pathogenesis, the immunological analyses indicated that CspZ is likely to have limited potential as a diagnostic marker and vaccine candidate for Lyme disease.
Role of Nod1 in Mucosal Dendritic Cells during
Salmonella
Pathogenicity Island 1-Independent
Salmonella enterica
Serovar Typhimurium Infection
Authors: Le Bourhis Lionel , Magalhaes Joao Gamelas , Selvanantham Thirumahal , Travassos Leonardo H. , Geddes Kaoru , Fritz Jörg H. , Viala Jérôme , Tedin Karsten , Girardin Stephen E. , Philpott Dana J. 
Published: July 2009

ABSTRACT

Recent advances in immunology have highlighted the critical function of pattern-recognition molecules (PRMs) in generating the innate immune response to effectively target pathogens. Nod1 and Nod2 are intracellular PRMs that detect peptidoglycan motifs from the cell walls of bacteria once they gain access to the cytosol.
Salmonella enterica
serovar Typhimurium is an enteric intracellular pathogen that causes a severe disease in the mouse model. This pathogen resides within vacuoles inside the cell, but the question of whether cytosolic PRMs such as Nod1 and Nod2 could have an impact on the course of
S
. Typhimurium infection in vivo has not been addressed. Here, we show that deficiency in the PRM Nod1, but not Nod2, resulted in increased susceptibility toward a mutant strain of
S
. Typhimurium that targets directly lamina propria dendritic cells (DCs) for its entry into the host. Using this bacterium and bone marrow chimeras, we uncovered a surprising role for Nod1 in myeloid cells controlling bacterial infection at the level of the intestinal lamina propria. Indeed, DCs deficient for Nod1 exhibited impaired clearance of the bacteria, both in vitro and in vivo, leading to increased organ colonization and decreased host survival after oral infection. Taken together, these findings demonstrate a key role for Nod1 in the host response to an enteric bacterial pathogen through the modulation of intestinal lamina propria DCs.