bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive ability of sequential surveys in determining donor loss from increasingly stringent variant Creutzfeldt‐Jakob disease deferral policies
Authors: O'Brien Sheila F. , Chiavetta Jo Anne , Goldman Mindy , Fan Wenli , Nair Rama C. , Sher Graham D. , Vamvakas Eleftherios C. 
Published: January 2006

BACKGROUND:  Predonation screening questions about travel increase the safety of the blood supply from diseases such as variant Creutzfeldt‐Jakob disease (vCJD) and malaria. This study examines the ability of sequential surveys to predict actual travel deferrals and the operational validity of travel questions.STUDY DESIGN AND METHODS:  To assess donor travel histories before implementing key deferral policies, two donor surveys were carried out at Canadian Blood Services collection sites in February 1999 (8026 donors) and March 2001 (13,623 donors). In‐person interviews were carried out with 1530 donors to assess the operational validity of the short travel question. Time‐series analysis was used to determine whether there was a change in deferrals when deferral policies were implemented. Predicted donor loss estimates based on survey results were compared with actual deferrals.RESULTS:  Deferrals increased significantly (p < 0.05) when vCJD deferral policies were implemented in October 1999 and September 2001, but not in October 2000. Survey data accurately predicted deferrals 6 months after implementation from the initial policy (2.51% predicted vs. 2.51% actual), but there were fewer deferrals than predicted for the second (2.89% predicted vs. 2.26% actual, p < 0.01) and third deferral policies (3.10% predicted vs. 1.89% actual, p < 0.01). There was 96 percent agreement between donor responses to a short screening question and a detailed travel history.CONCLUSION:  The initial survey accurately predicted the actual donor deferral rate, but the deferral rate was less than predicted for subsequent, more stringent donor deferral policies. Donors answered a short travel question suitable for donor screening similarly to a very detailed travel history.
Effects of skin disinfection method, deviation bag, and bacterial screening on clinical safety of platelet transfusions in the Netherlands
Authors: De Korte Dirk , Curvers Joyce , De Kort Wim L.A.M. , Hoekstra Tiny , Van Der Poel Cees L. , Beckers Erik A.M. , Marcelis Jan H. 
Published: January 2006

BACKGROUND:  Bacterial contamination of blood products is a great hazard for development of fatal transfusion reactions. Bacterial screening of platelet concentrates (PC) by aerobic and anaerobic culturing (BacT/ALERT, bioMérieux) was introduced in the Netherlands in October 2001.STUDY DESIGN AND METHODS:  In November 2002, a nationwide, uniform skin cleansing method was introduced with a double‐swab disinfection with 70 percent isopropyl alcohol. One location routinely used an integrated diversion bag to collect the first 20 to 30 mL.RESULTS:  Over the calendar years 2002 and 2003, in total 113,093 PCs derived from pooled buffy coats were screened. After introduction of the new disinfection method, 0.85 percent were initially positive. This was a small reduction compared to the previous disinfection methods under which 0.95 percent were initially positive. The location with use of the diversion bag showed a significantly lower frequency of bacterial contamination, with 0.50 percent before and 0.37 percent after introduction of 70 percent isopropyl alcohol. In addition 8000 apheresis PCs were also screened, showing 24 initially positive samples (0.30%).CONCLUSION:  The use of the diversion bag and, to a lesser extent, the use of double swabs with 70 percent isopropyl alcohol, led to a reduction of contamination. As expected, predominant contamination with resident skin bacteria was reduced. The combination of diversion bag and new disinfection led to a frequency of initial positive results for pooled five‐donor PCs, which is similar to that of single‐donor apheresis PCs. Furthermore, the bacterial detection system and associated product recall procedures have been shown to be effective in preventing transfusion of contaminated PCs and/or related red cells, especially for rapidly growing bacteria.
Composition and clinical use of hemodialysates
Authors: SAM Ramin , VASEEMUDDIN Mohammad , LEONG Wai Hong , ROGERS Brooks E. , KJELLSTRAND Carl M. , ING Todd S. 
Published: January 2006

AbstractA thorough knowledge and understanding of the principles underlying the preparation and the clinical application of hemodialysates can help us provide exemplary patient care to individuals having end‐stage renal disease. It is prudent to be conversant with the following: (a) how each ingredient in a dialysate works, (b) the clinical circumstances under which the concentration of an ingredient can be altered, and (c) the special situations in which unconventional ingredients can be introduced into a dialysate. The potential to enrich dialysates with appropriate ingredients (such as iron compounds) is limited only by the boundaries of our imagination.
Survival to discharge among patients treated with continuous renal replacement therapy
Authors: WALD Ron , DESHPANDE Rushi , BELL Chaim M. , BARGMAN Joanne M. 
Published: January 2006

AbstractContinuous renal replacement therapy (CRRT) is widely used in critically ill patients with acute renal failure (ARF). The survival of patients who require CRRT and the factors predicting their outcomes are not well defined. We sought to identify clinical features to predict survival in patients treated with CRRT. We reviewed the charts of all patients who received CRRT at the Toronto General Hospital during the year 2002. Our cohort (n=85) represented 97% of patients treated with this modality in 3 critical care units. We identified demographic variables, underlying diagnoses, transplantation status, location (medical‐surgical, coronary, or cardiovascular surgery intensive care units), CRRT duration, baseline estimated glomerular filtration rate (eGFR), and presence of oliguria (<400 mL/day) on the day of CRRT initiation. The principal outcome was survival to hospital discharge. Among those alive at discharge, we assessed whether there was an ongoing need for renal replacement therapy. Greater than one‐third (38%, 32/85) of patients survived to hospital discharge. Three (9%) survivors remained dialysis‐dependent at the time of discharge. Survivors were younger than nonsurvivors (mean age 56 vs. 60 years), were on CRRT for a shorter duration (7 vs. 13 days), and had a higher baseline eGFR (74 vs. 62 mL/min/m2). Patient survival varied among different critical care units (medical surgical 33%, coronary 38%, and cardiovascular surgery 45%). Multivariable logistic regression revealed that shorter duration of CRRT, nonoliguria, and baseline eGFR >60 mL/min/m2 were independently associated with survival to hospital discharge (p<0.05). Critically ill patients with ARF who require CRRT continue to have high in‐hospital mortality. A shorter period of CRRT dependence, nonoliguria and higher baseline renal function may predict a more favorable prognosis. The majority of CRRT patients who survive their critical illness are independent of dialysis at the time of hospital discharge.
Disturbances of antimicrobial lipids in atopic dermatitis
Authors: Melnik Bodo 
Published: January 2006

SummaryPatients with atopic dermatitis exhibit an increased susceptibility to cutaneous infections, especially to pathological colonization with superantigen‐secreting Staphylococcus aureus. Recent attention has been focused on antimicrobial peptides, especially on cathelicidin and human β‐defensin‐2, which are under‐expressed in atopic skin. Antimicrobial lipids from the stratum corneum are also major contributors to cutaneous antimicrobial defense. Current aspects of biochemistry and function of antimicrobial lipids in atopic dermatitis are reviewed in detail. The major classes of stratum corneum lipids with antimicrobial activity are free fatty acids, glucosylceramides, and free sphingosines. Diminished levels of free sphingosines in the stratum corneum have recently been detected in atopic dermatitis and have been associated with the pathological colonization of atopic skin with Staphylococcus aureus. The superantigen staphylococcal enterotoxin B has been shown to reduce the suppressive effect of regulatory T cells on T‐cell proliferation, thus augmenting T‐cell activation in patients with atopic dermatitis. The killing of superantigen‐secreting bacterial strains with topically applied antimicrobial lipids offers new antiseptic and immunomodulatory options for the treatment and secondary prevention of atopic dermatitis.
New therapeutic approaches for solid tumors: Histone deacetylase, methyltransferase and proteasome inhibitors
Authors: Becker Jürgen C. , Ugurel Selma , Bröcker Eva‐Bettina , Schrama David , Houben Roland 
Published: January 2006

SummaryRecent results from basic and translational research on tumor genesis and progression establish the basis for future therapeutic approaches. Targeted therapeutics are tailored toward the molecular abnormalities that cause tumor progression and could potentially provide an effective, non‐toxic therapeutic approach in a broad range of cancers including melanoma. Cancer is as much a (cyto)genetic disease as it is an epigenetic disease. Indeed, the fate of the cell depends on a delicate balance between expression and repression of genes. The notion that drastic changes in DNA methylation and histone modifications are present in a variety of human tumors has prompted the development and characterization of epigenetic drugs. Inhibitors of histone deacetylases and methyltransferases as well as of the proteasome are covered in this review.
An investigation into the physiological relevance of the vagal tachycardia in the anaesthetized dog
Authors: Markos F. , Snow H. M. 
Published: January 2006

AbstractAim:  Our aim was primarily to assess whether or not a vagal tachycardia can be elicited in vivo without administration of atropine, and secondly to evaluate whether the dose of atropine, a muscarinic antagonist, determines the magnitude of the tachycardia.Methods:  Experiments were carried out in the presence of atenolol (2 mg kg−1). The vagal tachycardia requires high vagal activity which was induced by noradrenaline infusion (20 μg min−1). Two techniques were then used to elicit a tachycardia, vagal section and atropine administration.Results:  The increase in blood pressure caused heart rate to fall to 60 ± 7 beats min−1 (mean ± SEM). When the vagi were sectioned (n = 5) heart rate increased by 9 ± 2 beats min−1 above the intrinsic rate which was 108 beats min−1, this increase was not significant. In contrast atropine given (9–20 μg kg−1) (n = 5) during high vagal activity increased heart rate by 81 ± 22 beats min−1 above the intrinsic rate (P < 0.05). To assess if the dose of atropine affects the magnitude of the vagal tachycardia, the right vagus was stimulated electrically at increasing frequencies (2, 4, 8, 16, 32 Hz) before and after increasing doses of atropine (0.02, 0.05, 1 mg kg−1). This reduced the magnitude of the bradycardia; however, the magnitude of the vagal tachycardia was unaffected.Conclusion:  The vagal tachycardia cannot be elicited without atropine suggesting that it does not play a significant physiological role.
How we do it: Patient participation in cochlear implant selection
Authors: Geyer M. , Seymour F.K. , Stott L. , Lynch C. , Beukes M. , Aleksy W. , Graham J.M. 
Published: January 2006

Keypoints• Involving patients and parents in the choice of their cochlear implant encourages an active role in the process and facilitates ‘bonding’ and ‘ownership’ of the device.• The most frequent reasons given by patients for selecting a device included cochlear implant comfort and appearance.• We describe the Implant Programme based at the Royal National Throat, Nose and Ear Hospital, London, and also examine patient satisfaction with the scheme.
The evidence base for the application of contralateral bone anchored hearing aids in acquired unilateral sensorineural hearing loss in adults
Authors: Baguley D.M. , Bird J. , Humphriss R.L. , Prevost A.T. 
Published: January 2006

Keypoints• Acquired unilateral sensorineural hearing loss reduces the ability to localize sounds and to discriminate in background noise.• Four controlled trials attempt to determine the benefit of contralateral bone anchored hearing aids over contralateral routing of signal (CROS) hearing aids and over the unaided condition. All found no significant improvement in auditory localization with either aid. Speech discrimination in noise and subjective questionnaire measures of auditory abilities showed an advantage for bone anchored hearing aid (BAHA) > CROS > unaided conditions.• All four studies have material shortfalls:  (i) the BAHA was always trialled after the CROS aid;  (ii) CROS aids were only trialled for 4 weeks;  (iii) none used any measure of hearing handicap when selecting subjects;  (iv) two studies have a bias in terms of patient selection;  (v) all studies were underpowered  (vi) double reporting of patients occurred.• There is a paucity of evidence to support the efficacy of BAHA in the treatment of acquired unilateral sensorineural hearing loss. Clinicians should proceed with caution and perhaps await a larger randomized trial.• It is perhaps only appropriate to insert a BAHA peg at the time of vestibular schwanoma tumour excision in patients with good preoperative hearing, as their hearing handicap increases most.
A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques
Authors: Capone Stefania , Meola Annalisa , Ercole Bruno Bruni , Vitelli Alessandra , Pezzanera Monica , Ruggeri Lionello , Davies Mary Ellen , Tafi Rosalba , Santini Claudia , Luzzago Alessandra , Fu Tong-Ming , Bett Andrew , Colloca Stefano , Cortese Riccardo , Nicosia Alfredo , Folgori Antonella 
Published: January 2006

ABSTRACT

Success in resolving hepatitis C virus (HCV) infection has been correlated to vigorous, multispecific, and sustained CD8
+
T-cell response in humans and chimpanzees. The efficacy of inducing T-cell-mediated immunity by recombinant serotype 5 adenovirus vector has been proven in many animal models of infectious diseases, but its immunogenicity can be negatively influenced by preexisting immunity against the vector itself. To evaluate the less prevalent adenovirus serotype 6 (Ad6) as an alternative vector for and HCV vaccine development, we have generated serotype 5 and 6 adenoviral vectors directing expression of the nonstructural region of HCV (MRKAd5-NSmut and MRKAd6-NSmut). Immunogenicity studies in mice showed that the two vectors induced comparable T-cell responses but that only MRKAd6-NSmut was not suppressed in the presence of anti-Ad5 immunity. In contrast, preexisting anti-Ad5 immunity dramatically blunted the immunogenicity of the serotype 5-based HCV vector. Furthermore, MRKAd6-NSmut showed equivalent potency, breadth, and longevity of HCV-specific T-cell responses in rhesus macaques as the corresponding Ad5-based vector over a wide range of doses and was capable of boosting DNA-primed animals even if administered at low doses. These data support the use of the MRKAd6-NSmut for anti-HCV immunotherapy and, more generally, for the Ad6 serotype as a better genetic vaccine vehicle than Ad5.
Function of Small Hydrophobic Proteins of Paramyxovirus
Authors: Wilson Rebecca L. , Fuentes Sandra M. , Wang Ping , Taddeo Erica C. , Klatt Alicia , Henderson Andrew J. , He Biao 
Published: January 2006

ABSTRACTMumps virus (MuV), a rubulavirus of the paramyxovirus family, causes acute infections in humans. MuV has seven genes including a small hydrophobic (SH) gene, which encodes a type I membrane protein of 57 amino acid residues. The function of the SH protein is not clear, although its expression is not necessary for growth of MuV in tissue culture cells. It is speculated that MuV SH plays a role in viral pathogenesis. Simian virus 5 (SV5), a closely related rubulavirus, encodes a 44-amino-acid-residue SH protein. Recombinant SV5 lacking the SH gene (rSV5ΔSH) is viable and has no growth defect in tissue culture cells. However, rSV5ΔSH induces apoptosis in tissue culture cells and is attenuated in vivo. Neutralizing antibodies against tumor necrosis factor alpha (TNF-α) and TNF-α receptor 1 block rSV5ΔSH-induced apoptosis, suggesting that SV5 SH plays an essential role in blocking the TNF-α-mediated apoptosis pathway. Because MuV is closely related to SV5, we hypothesize that the SH protein of MuV has a function similar to that of SV5, even though there is no sequence homology between them. To test this hypothesis and to study the function of MuV SH, we have replaced the open reading frame (ORF) of SV5 SH with the ORF of MuV SH in a SV5 genome background. The recombinant SV5 (rSV5ΔSH+MuV-SH) was analyzed in comparison with SV5. It was found that rSV5ΔSH+MuV-SH was viable and behaved like wild-type SV5, suggesting that MuV SH has a function similar to that of SV5 SH. Furthermore, both ectopically expressed SV5 SH and MuV SH blocked activation of NF-κB by TNF-α in a reporter gene assay, suggesting that both SH proteins can inhibit TNF-α signaling.
Characterization of the Role of Very Late Expression Factor 1 in Baculovirus Capsid Structure and DNA Processing
Authors: Vanarsdall Adam L. , Okano Kazuhiro , Rohrmann George F. 
Published: January 2006

ABSTRACT

Very late expression factor 1 (VLF-1) of
Autographa californica
multiple nucleopolyhedrovirus is a putative tyrosine recombinase and is required for both very late gene expression and budded virus production. In this report, we show that a
vlf-1
knockout bacmid was able to synthesize viral DNA at levels similar to that detected for a
gp64
knockout bacmid that served as a noninfectious control virus. Additionally, analysis of replicated bacmid DNA by field-inversion gel electrophoresis indicated that VLF-1 is not required for synthesizing high-molecular-weight intermediates that could be resolved into unit-length genomes when cut at a unique restriction site. However, immunoelectron microscopic analysis revealed that in cells transfected with a
vlf-1
knockout bacmid, aberrant tubular structures containing the capsid protein vp39 were observed, suggesting that this virus construct was defective in producing mature capsids. In contrast, rescuing the
vlf-1
knockout bacmid construct with a copy of VLF-1 that carries a mutation of a highly conserved tyrosine (Y355F) was sufficient to restore the production of nucleocapsids with a normal appearance, but not infectious virus production. Furthermore, the results of a DNase I protection assay indicated that the DNA packaging efficiency of the VLF-1(Y355F) virus construct was similar to that of the
gp64
knockout control. Finally, a recombinant virus containing a functional hemagglutinin epitope-tagged version of VLF-1 was constructed to investigate the association of VLF-1 with the nucleocapsid. Analysis by immunoelectron microscopy of Sf-9 cells infected with this virus showed that VLF-1 localized to an end region of the nucleocapsid. Collectively, these results indicate that VLF-1 is required for normal capsid assembly and serves an essential function during the final stages of the DNA packaging process.
Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry
Authors: Tscherne Donna M. , Jones Christopher T. , Evans Matthew J. , Lindenbach Brett D. , McKeating Jane A. , Rice Charles M. 
Published: January 2006

ABSTRACT
Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. In this study, we used cell culture-produced infectious HCV to analyze the viral entry pathway into Huh-7.5 cells. Bafilomycin A1 and concanamycin A, inhibitors of vacuolar ATPases, prevented HCV entry when they were present prior to infection and had minimal effect on downstream replication events. HCV entry therefore appears to be pH dependent, requiring an acidified intracellular compartment. For many other enveloped viruses, acidic pH triggers an irreversible conformational change, which promotes virion-endosomal membrane fusion. Such viruses are often inactivated by low pH. In the case of HCV, exposure of virions to acidic pH followed by return to neutral pH did not affect their infectivity. This parallels the observation made for the related pestivirus bovine viral diarrhea virus. Low pH could activate the entry of cell surface-bound HCV but only after prolonged incubation at 37°C. This suggests that there are rate-limiting, postbinding events that are needed to render HCV competent for low-pH-triggered entry. Such events may involve interaction with a cellular coreceptor or other factors but do not require cathepsins B and L, late endosomal proteases that activate Ebola virus and reovirus for entry.
Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines
Authors: Stone Geoffrey W. , Barzee Suzanne , Snarsky Victoria , Kee Kristin , Spina Celsa A. , Yu Xiao-Fang , Kornbluth Richard S. 
Published: January 2006

ABSTRACTFor use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule. Soluble trimeric forms of CD40L have been produced, but in vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more active. This multimerization requirement was evaluated in mice using plasmids that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L. Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form. Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4). These CD40L-augmented DNA vaccines elicited strong CD8+T-cell responses but did not elicit significant CD4+T-cell or antibody responses. To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL) augmented the CD8+T-cell, CD4+T-cell, and antibody responses to DNA vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the rapid testing of TNFSF molecules in vivo.