bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychiatric genetic counselling for parents of individuals affected with psychotic disorders: a pilot study
Authors: Austin Jehannine C. , Honer William G. 
Published: April 2008

AbstractAim: There has been increasing interest in the concept of applying genetic counselling to psychiatric disorders, but despite its relevance to psychiatric illness, and interest from the target group, there have been no empiric investigations of psychiatric genetic counselling. In a population of unaffected parents of individuals with first episode as well as more chronic psychotic disorders, we aimed to investigate whether psychiatric genetic counselling: is perceived to be useful, could increase understanding of the causes of psychiatric illness and decrease concern about other relatives becoming affected.Methods: Subjects (n = 13) participated in a genetic counselling session. The session was a clinical intervention similar to what would be carried out as part of a referral for any disease with a hereditary component, but specific for psychosis. Questionnaires were used to assess (pre‐counselling): motivations for attending, concern about other relatives developing psychiatric illness, and (post‐counselling) whether the intervention: (i) improved understanding of mental illness; (ii) modified concern about other relatives becoming affected; and (iii) was perceived to be useful.Results: Desire for knowledge motivated participation. Immediately after the session, and 1 month later >92% and 100% of participants, respectively, felt that the session was useful. Genetic counselling reduced concern about other relatives becoming affected as risks were lower than participants had expected. All participants felt that their understanding of the causes of psychiatric illness had improved through genetic counselling.Conclusion: Psychiatric genetic counselling may benefit parents of individuals with psychiatric illnesses. Avenues for future research are highlighted.
Providing online support for young people with mental health difficulties: challenges and opportunities explored
Authors: Webb Marianne , Burns Jane , Collin Philippa 
Published: April 2008

AbstractDespite its growing popularity there is a paucity of information exploring the potential of the Internet to build a trusted community that helps reduce stigma, facilitates help‐seeking and aids in the prevention or helps in the management of mental health difficulties for young people. Unsupervised online forums or chat rooms hold potential dangers for young people including the possibility of attracting adults who may take advantage of vulnerable adolescents. Contagion with members organizing suicide pacts, or describing suicidal or self‐harming intentions and methods and young people ruminating about feeling depressed are also potential risks. This paper describes the development and conceptual underpinnings of the Reach Out! Online Community Forum, a moderated bulletin board, developed in consultation with, and facilitated by young people aged 16–25. The Forum, although facilitated by young people, is supported and monitored by trained moderators. Anecdotal evidence collected via unsolicited feedback from young people using the Forum suggests that it is a positive, unique and helpful online experience although little is known about the impact on stigma reduction and help seeking in the offline world. Given the proliferation of unsupervised forums and chat rooms there is a need for further research to determine the effectiveness or potential dangers of online forums in mental health prevention and early intervention work.
ON INFLATION
Authors: Mohr Philiph 
Published: April 2008

AbstractThere is currently much more common sense in the South African inflation debate than a few decades ago. In particular, the South African Reserve Bank exhibits a pragmatic, eclectic approach to inflation (as reflected in its bi‐annual Monetary Policy Reports). This is in stark contrast to the narrow, monetarist‐type thinking that tended to dominate during the 1980s.This paper is an attempt to contribute to the debate by highlighting a few issues, including the widespread substitution of the CPI by the CPIX, the fact that inflation is a process, the need to combat inflation, the causes of the decline in inflation in South Africa and the essential features of an inflation‐targeting framework for monetary policy.
Presence of Plasmid-Mediated Quinolone Resistance in
Klebsiella pneumoniae
Isolates Possessing
bla
KPC
in the United States
Authors: Endimiani Andrea , Carias Lenore L. , Hujer Andrea M. , Bethel Christopher R. , Hujer Kristine M. , Perez Federico , Hutton Rebecca A. , Fox William R. , Hall Geraldine S. , Jacobs Michael R. , Paterson David L. , Rice Louis B. , Jenkins Stephen G. , Tenover Fred C. , Bonomo Robert A. 
Published: April 2008

ABSTRACT

The presence of plasmid-mediated quinolone resistance genes [i.e.,
qnrA
,
qnrB
,
qnrS
,
aac(6
′
)-Ib-cr
, and
qepA
] was evaluated among 42
bla
KPC
-containing
Klebsiella pneumoniae
isolates collected in the eastern United States. One isolate carried the
bla
KPC-3
and
qnrB19
genes on the same conjugative plasmid, whereas another carried the
bla
KPC-3
and
qnrA1
genes on separate plasmids.
Telavancin Penetration into Human Epithelial Lining Fluid Determined by Population Pharmacokinetic Modeling and Monte Carlo Simulation
Authors: Lodise Thomas P. , Gotfried Mark , Barriere Steven , Drusano George L. 
Published: April 2008

ABSTRACT

Telavancin is an investigational bactericidal lipoglycopeptide with a multifunctional mechanism of action, as demonstrated against methicillin-resistant
Staphylococcus aureus
. While the plasma pharmacokinetics have been described, the extent of the penetration of the drug into the lung, measured by the epithelial lining fluid (ELF), remains unknown. Population modeling and Monte Carlo simulation were employed to estimate the penetration of telavancin into ELF. Plasma and ELF pharmacokinetic data were obtained from 20 healthy volunteers, and the pharmacokinetic samples were assayed by a validated liquid chromatography-tandem mass spectrometry technique. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer. The model parameters were identified in a population pharmacokinetic analysis (BigNPAG). Monte Carlo simulation of 9,999 subjects was performed to calculate the ELF/plasma penetration ratios by estimating the area under the concentration-time curve (AUC) for the drug in ELF (AUC
ELF
) and for the free drug in plasma (free AUC
plasma
) from zero to infinity after a single dose. After the Bayesian step, the overall fits of the model to the data were good, and plots of predicted versus observed concentrations in plasma and ELF showed slopes and intercepts very close to the ideal values of 1.0 and 0.0, respectively. The median AUC
ELF
/free AUC
plasma
penetration ratio was 0.73, and the 25th and 75th percentile value ratios were 0.43 and 1.24, respectively. In uninfected lung tissue, the median AUC
ELF
is approximately 75% of the free AUC
plasma
.
In Vitro Antibacterial Activity of CE-156811, a Novel Analog Derived from Hygromycin A
Authors: Stone Gregory G. , Girard Dennis , Finegan Steve , Duignan Joan , Schafer John , Maloney Meghan , Zaniewski Richard P. , Brickner Steven J. , Wade Sarah K. , Le Phuong T. , Huband Michael D. 
Published: April 2008

ABSTRACTWe evaluated a novel truncated hygromycin A analog in which the furanose ring was replaced with a 2-fluoro-2-cyclopropylethyl substituent for its activity against multidrug resistant gram-positive bacteria and compared its activity to the activities of linezolid, quinupristin-dalfopristin, and vancomycin. CE-156811 demonstrated robust in vitro activity against gram-positive bacteria that was comparable to that of linezolid.
Francisella tularensisInvasion of Lung Epithelial Cells
Authors: Craven Robin R. , Hall Joshua D. , Fuller James R. , Taft-Benz Sharon , Kawula Thomas H. 
Published: April 2008

ABSTRACTFrancisella tularensis, a gram-negative facultative intracellular bacterial pathogen, causes disseminating infections in humans and other mammalian hosts. Macrophages and other monocytes have long been considered the primary site ofF. tularensisreplication in infected animals. However, recently it was reported thatF. tularensisalso invades and replicates within alveolar epithelial cells following inhalation in a mouse model of tularemia. TC-1 cells, a mouse lung epithelial cell line, were used to study the process ofF. tularensisinvasion and intracellular trafficking within nonphagocytic cells. Live and paraformaldehyde-fixedF. tularensislive vaccine strain organisms associated with, and were internalized by, TC-1 cells at similar frequencies and with indistinguishable differences in kinetics. Inhibitors of microfilament and microtubule activity resulted in significantly decreasedF. tularensisinvasion, as did inhibitors of phosphatidylinositol 3-kinase and tyrosine kinase activity. Collectively, these results suggest thatF. tularensisepithelial cell invasion is mediated by a preformed ligand on the bacterial surface and driven entirely by host cell processes. Once internalized,F. tularensis-containing endosomes associated with early endosome antigen 1 (EEA1) followed by lysosome-associated membrane protein 1 (LAMP-1), with peak coassociation frequencies occurring at 30 and 120 min postinoculation, respectively. By 2 h postinoculation, 70.0% (± 5.5%) of intracellular bacteria were accessible to antibody delivered to the cytoplasm, indicating vacuolar breakdown and escape into the cytoplasm.
The Cytosolic Pattern Recognition Receptor NOD1 Induces Inflammatory Interleukin-8 duringChlamydia trachomatisInfection
Authors: Buchholz Kerry R. , Stephens Richard S. 
Published: April 2008

ABSTRACTInflammation is a hallmark of chlamydial infections, but how inflammatory cytokines are induced is not well understood. Pattern recognition receptors (PRR) of the host innate immune system recognize pathogen molecules and activate intracellular signaling pathways that modulate immune responses. The role of PRR such as Toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD) proteins in the endogenous interleukin-8 (IL-8) response induced duringChlamydia trachomatisinfection is not known. We hypothesized that a PRR is essential for the IL-8 response induced byC. trachomatisinfection. RNA interference was used to knock down the TLR signaling partner MyD88 as well as NOD1 and its signaling molecule receptor-interacting protein 2 (RIP2). IL-8 induced at 30 h postinfection byC. trachomatiswas dependent on NOD1 signaling through RIP2; however, the IL-8 response was independent of MyD88-dependent TLR signaling. Activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cellular signaling pathway, which is essential for up-regulation of IL-8 in response toC. trachomatisinfection, was independent of NOD1 or RIP2. We conclude that the endogenous IL-8 response induced byC. trachomatisinfection is dependent upon NOD1 PRR signaling through RIP2 as part of a signal system requiring multiple inputs for optimal IL-8 induction. Since ERK is not activated through this pathway, a concomitant interaction between the host and bacteria is additionally required for full activation of the endogenous IL-8 response.
Novel Role of Sphingolipid Synthesis Genes in Regulating Giardial Encystation
Authors: Hernandez Yunuen , Shpak Max , Duarte Trevor T. , Mendez Tavis L. , Maldonado Rosa A. , Roychowdhury Sukla , Rodrigues Marcio L. , Das Siddhartha 
Published: April 2008

ABSTRACTAlthough encystation (cyst formation) is important for the survival ofGiardia lambliaoutside its human host, the molecular events that prompt encystation have not been fully elucidated. Here, we demonstrate that sphingolipids (SLs), which are important for the growth and differentiation of many eukaryotes, play key roles in giardial encystation. Transcriptional analyses showed that only three genes in the SL biosynthesis pathways are expressed and transcribed differentially in nonencysting and encystingGiardiatrophozoites. While the putative homologues of giardial serine palmitoyltransferase (gSPT) subunit genes (gspt-1and -2) are differentially expressed in nonencysting and encysting trophozoites, the giardial ceramide glucosyltransferase 1 gene (gglct-1) is transcribed only in encysting cells.l-Cycloserine, an inhibitor of gSPT, inhibited the endocytosis and endoplasmic reticulum/perinuclear targeting of bodipy-ceramide in trophozoites, and this could be reversed by 3-ketosphinganine. On the other hand,d-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), an inhibitor of glucosylceramide synthesis, blocked karyokinesis and reduced cyst production in culture. PPMP also altered the expression of cyst wall protein transcripts in encysting cells. Phylogenetic analyses revealed that thegsptgenes are paralogs derived from an ancestralsptsequence that underwent gene duplication early in eukaryotic history. This ancestral sequence, in turn, was probably derived from prokaryotic aminoacyl transferases. In contrast,gglct-1is found in both prokaryotes and eukaryotes without any evidence of gene duplication. These studies indicate that SL synthesis genes are involved in key events in giardial biology and could serve as potential targets for developing new therapies against giardiasis.
Pilot-Scale Production and Characterization of Paramyosin, a Vaccine Candidate for Schistosomiasis Japonica
Authors: Jiz Mario , Wu Hai-Wei , Meng Rui , Pond-Tor Sunthorn , Reynolds Mindy , Friedman Jennifer F. , Olveda Remigio , Acosta Luz , Kurtis Jonathan D. 
Published: April 2008

ABSTRACTDespite effective chemotherapy, schistosomiasis remains a major public health problem in the developing world, with at least 200 million active infections resulting in significant morbidity. Rapid reinfection after treatment, accompanied by extensive residual morbidity, mandates alternative control strategies, including vaccine development. Paramyosin, a myofibrillar protein found only in invertebrates, has been widely studied as a vaccine candidate for bothSchistosoma mansoniandSchistosoma japonicum. Recently, we demonstrated that Th2-biased immune responses to paramyosin are associated with resistance to reinfection withS. japonicumin humans; however, challenges in the pilot-scale production of schistosome paramyosin have hampered further studies of this promising vaccine candidate. Here we report a method for the pilot-scale expression and purification of recombinantS. japonicumparamyosin (rSj97). rSj97 was extracted fromEscherichia coliinclusion bodies and purified with sequential anion-exchange, hydroxyapatite, and size exclusion chromatography. The purified rSj97 was >95% pure as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis and was free of significant endotoxin contamination. We demonstrate that, like native paramyosin, rSj97 adopts an alpha-helical coiled-coil tertiary structure and binds immunoglobulin and collagen. Naïve mice infected withS. japonicumproduce anti-rSj97 immunoglobulin G (IgG) antibodies as early as 4 weeks postinfection, while sera collected fromS. japonicum-infected individuals contain anti-rSj97 IgE antibodies. Our method for pilot-scale production of recombinant full-length paramyosin will facilitate preclinical evaluation of paramyosin as a vaccine for schistosomiasis.
Toll-Like Receptor 9 Regulates the Lung Macrophage Phenotype and Host Immunity in Murine Pneumonia Caused byLegionella pneumophila
Authors: Bhan Urvashi , Trujillo Glenda , Lyn-Kew Kenneth , Newstead Michael W. , Zeng Xianying , Hogaboam Cory M. , Krieg Arthur M. , Standiford Theodore J. 
Published: April 2008

ABSTRACTExperiments were performed to determine the contribution of TLR9 to the generation of protective immunity against the intracellular respiratory bacterial pathogenLegionella pneumophila. In initial studies, we found that the intratracheal (i.t.) administration ofL. pneumophilato mice deficient in TLR9 (TLR9−/−) resulted in significantly increased mortality, which was associated with an approximately 10-fold increase in the number of lung CFU compared to that of wild-type BALB/c mice. Intrapulmonary bacterial challenge in TLR9−/−mice resulted in the reduced accumulation of myeloid dendritic cells (DC) and activated CD4+T cells. Lung macrophages isolated fromLegionella-infected TLR9−/−mice displayed the impaired internalization of bacteria and evidence of alternative rather than classical activation, as manifested by the markedly reduced expression of nitric oxide and type 1 cytokines, whereas the expression of Fizz-1 and arginase-1 was enhanced. The adoptive transfer of bone marrow-derived DC from syngeneic wild-type, but not TLR9−/−, mice administered i.t. reconstituted anti-legionella immunity and restored the macrophage phenotype in TLR9−/−mice. Finally, the i.t., but not intraperitoneal, administration of the TLR9 agonist molecule CpG oligodeoxynucleotide stimulated protective immunity inLegionella-infected mice. In total, our findings indicate that TLR9 is required for effective innate immune responses against the intracellular bacterial pathogenL. pneumophila, and approaches to maximize TLR9-mediated responses may serve as a means to augment antibacterial immunity in pneumonia.
Nasal Immunization with
Porphyromonas gingivalis
Outer Membrane Protein Decreases
P. gingivalis
-Induced Atherosclerosis and Inflammation in Spontaneously Hyperlipidemic Mice
Authors: Koizumi Y. , Kurita-Ochiai T. , Oguchi S. , Yamamoto M. 
Published: April 2008

ABSTRACT

Porphyromonas gingivalis
has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against
P. gingivalis
infection for the prevention of atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe
shl
) mice were nasally immunized with the 40-kDa outer membrane protein (OMP) of
P. gingivalis
plus cholera toxin (CT) as adjuvant and then challenged intravenously with
P. gingivalis
strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40-kDa OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe
shl
mice challenged with
P. gingivalis
compared to nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic infection with
P. gingivalis
accelerates atherosclerosis in Apoe
shl
mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by
P. gingivalis
in the hyperlipidemic mouse model.
Metal Binding Specificity of the MntABC Permease ofNeisseria gonorrhoeaeand Its Influence on Bacterial Growth and Interaction with Cervical Epithelial Cells
Authors: Lim Karen H. L. , Jones Christopher E. , vanden Hoven Rachel N. , Edwards Jennifer L. , Falsetta Megan L. , Apicella Michael A. , Jennings Michael P. , McEwan Alastair G. 
Published: April 2008

ABSTRACTmntABCfromNeisseria gonorrhoeaeencodes an ABC permease which includes a periplasmic divalent cation binding receptor protein of the cluster IX family, encoded bymntC. Analysis of anmntCmutant showed that growth ofN. gonorrhoeaecould be stimulated by addition of either manganese(II) or zinc(II) ions, suggesting that the MntABC system could transport both ions. In contrast, growth of themntABmutant in liquid culture was possible only when the medium was supplemented with an antioxidant such as mannitol, consistent with the view that ion transport via MntABC is essential for protection ofN. gonorrhoeaeagainst oxidative stress. Using recombinant MntC, we determined that MntC binds Zn2+and Mn2+with almost equal affinity (dissociation constant of ∼0.1 μM). Competition assays with the metallochromic zinc indicator 4-(2-pyridylazo)resorcinol showed that MntC binds Mn2+and Zn2+at the same binding site. Analysis of theN. gonorrhoeaegenome showed that MntC is the only Mn/Zn metal binding receptor protein cluster IX in this bacterium, in contrast to the situation in many other bacteria which have systems with dedicated Mn and Zn binding proteins as part of distinctive ABC cassette permeases. Both themntCandmntABmutants had reduced intracellular survival in a human cervical epithelial cell model and showed reduced ability to form a biofilm. These data suggest that the MntABC transporter is of importance for survival ofNeisseria gonorrhoeaein the human host.
Quality Control Assessment of Human Immunodeficiency Virus Type 2 (HIV-2) Viral Load Quantification Assays: Results from an International Collaboration on HIV-2 Infection in 2006
Authors: Damond Florence , Benard Antoine , Ruelle Jean , Alabi Abraham , Kupfer Bernd , Gomes Perpetua , Rodes Berta , Albert Jan , Böni Jürg , Garson Jeremy , Ferns Bridget , Matheron Sophie , Chene Geneviève , Brun-Vezinet Françoise 
Published: April 2008

ABSTRACT

Human immunodeficiency virus type 2 (HIV-2) RNA quantification assays used in nine laboratories of the ACHI
E
V
2E
(A Collaboration on HIV-2 Infection) study group were evaluated. In a blinded experimental design, laboratories quantified three series of aliquots of an HIV-2 subtype A strain, each at a different theoretical viral load. Quantification varied between laboratories, and international standardization of quantification assays is strongly needed.
Structural Analysis of Human Immunodeficiency Virus Type 1 CRF01_AE Protease in Complex with the Substrate p1-p6
Authors: Bandaranayake Rajintha M. , Prabu-Jeyabalan Moses , Kakizawa Junko , Sugiura Wataru , Schiffer Celia A. 
Published: April 2008

ABSTRACT
The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 Å. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.