bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron deficiency in Canadian blood donors
Authors: Goldman Mindy , Uzicanin Samra , Scalia Vito , O'Brien Sheila F. 
Published: August 2013

BackgroundThe adequacy of communication and knowledge of donors and physicians regarding iron needs and the relationship between hemoglobin (Hb) and iron stores require evaluation to address donor iron deficiency.Study Design and MethodsA prospective cohort study was performed on 550 successful donors and 50 donors deferred for low Hb (<125 g/L on repeat fingerstick). Donors participated in an on‐clinic interview and had serum ferritin measured. They were mailed their results and recontacted regarding follow‐up.ResultsMost donors are unaware of possible health impacts of donation and do not discuss donation with their physician. In successful donors, mean ferritin levels were 37 and 131 μg/L in first‐time and reactivated (no donation for 2 years) females and males and 19 and 29 μg/L in frequent repeat females and males, respectively (p < 0.0001), with infrequent donors having intermediate results. Mean ferritin was 12 μg/L in donors deferred for low Hb. Twenty of 22 donors failing initial Hb testing and passing on repeat testing had ferritin below 25 μg/L. On follow‐up, 63 of 164 donors (38%) with low ferritin were taking iron supplements 2 months postdonation.ConclusionIron deficiency is frequent, particularly in female donors and frequent donors. A fail on initial Hb testing followed by a pass on repeat testing is likely to be due to iron deficiency and borderline anemia. Donors and physicians need to be more aware of iron needs associated with blood donation and appropriate treatment for low iron stores.
Addition of plerixafor for CD34+ cell mobilization in six healthy stem cell donors ensured satisfactory grafts for transplantation
Authors: Hauge Anne Werner , Haastrup Eva Kannik , Sengeløv Henrik , Minulescu Lia , Dickmeiss Ebbe , Fischer‐Nielsen Anne 
Published: August 2013

BackgroundIn allogeneic hematopoietic stem cell (HSC) transplantation, collection of a sufficient number of HSCs at a fixed time point is crucial. For HSC mobilization into the peripheral blood, the standard regimen, that is, granulocyte–colony‐stimulating factor (G‐CSF), may be inadequate. Use of plerixafor as adjuvant to G‐CSF is so far off‐label in healthy donors.Study Design and MethodsWe present six cases in which the “just‐in‐time” addition of plerixafor ensured proper CD34+ collection from healthy donors with insufficient G‐CSF mobilization. In four of these cases a high number of CD34+ cells was needed due to subsequent CD34+ selection or haploidentical transplantation.ResultsFrom all six donors a sufficient number of CD34+ cells was obtained by using plerixafor as an adjuvant to G‐CSF. This treatment regimen resulted in only mild side effects for the donor.ConclusionWe have presented six cases with different causes leading to insufficient G‐CSF mobilization in allogeneic donors and in which the administration of plerixafor just‐in‐time ensured a proper graft for transplantation.
Antibody-Secreting Cell Responses after Vibrio cholerae O1 Infection and Oral Cholera Vaccination in Adults in Bangladesh
Authors: Rahman Atiqur , Rashu Rasheduzzaman , Bhuiyan Taufiqur Rahman , Chowdhury Fahima , Khan Ashraful Islam , Islam Kamrul , LaRocque Regina C. , Ryan Edward T. , Wrammert Jens , Calderwood Stephen B. , Qadri Firdausi , Harris Jason B. 
Published: August 2013

ABSTRACTInfection withVibrio choleraeand oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels ofV. cholerae-specific duodenal antibodies up to 6 months afterV. choleraeinfection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses followingV. choleraeinfection using a flow cytometrically defined population and comparedV. cholerae-specific responses in adult patients withV. choleraeO1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) orV. choleraeO1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection withV. choleraeO1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after naturalV. choleraeinfection. A second dose of OCV on day 14 failed to boost circulatingV. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas whereV. choleraeinfection is endemic and those where it is not.
Seroepidemiologies of Human Metapneumovirus and Respiratory Syncytial Virus in Young Children, Determined with a New Recombinant Fusion Protein Enzyme-Linked Immunosorbent Assay
Authors: Dunn Sarah R. , Ryder Alex B. , Tollefson Sharon J. , Xu Meng , Saville Benjamin R. , Williams John V. 
Published: August 2013

ABSTRACTWe compared antibodies against human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) in children. The antibody nadirs for both viruses were at 3 to 5 months, and the majority of children were seropositive for both by 2 years. There was no significant difference in the kinetics of maternal antibody decline or seroconversion relative to the two viruses.
Application of a Newly Developed High-Sensitivity HBsAg Chemiluminescent Enzyme Immunoassay for Hepatitis B Patients with HBsAg Seroclearance
Authors: Shinkai Noboru , Matsuura Kentaro , Sugauchi Fuminaka , Watanabe Tsunamasa , Murakami Shuko , Iio Etsuko , Ogawa Shintaro , Nojiri Shunsuke , Joh Takashi , Tanaka Yasuhito 
Published: August 2013

ABSTRACTWe modified and automated a highly sensitive chemiluminescent enzyme immunoassay (CLEIA) for surface antigen (HBsAg) detection using a combination of monoclonal antibodies, each for a specific epitope of HBsAg, and by improving an earlier conjugation technique. Of 471 hepatitis B virus (HBV) carriers seen in our hospital between 2009 and 2012, 26 were HBsAg seronegative as determined by the Abbott Architect assay. The Lumipulse HBsAg-HQ assay was used to recheck those 26 patients who demonstrated seroclearance by the Abbott Architect assay. The performance of the Lumipulse HBsAg-HQ assay was compared with that of a quantitative HBsAg detection system (Abbott Architect) and the Roche Cobas TaqMan HBV DNA assay (CTM) (lower limit of detection, 2.1 log copies/ml) using blood serum samples from patients who were determined to be HBsAg seronegative by the Abbott Architect assay. Ten patients had spontaneous HBsAg loss. Of 8 patients treated with nucleotide analogues (NAs), two were HBsAg seronegative after stopping lamivudine therapy and 6 were HBsAg seronegative during entecavir therapy. Eight acute hepatitis B (AH) patients became HBsAg seronegative. Of the 26 patients, 16 were HBsAg positive by the Lumipulse HBsAg-HQ assay but negative by the Abbott Architect assay. The differences between the two assays in terms of detectable HBsAg persisted over the long term in the spontaneous loss group (median, 10 months), the NA-treated group (2.5 months), and the AH group (0.5 months). In 9 patients, the Lumipulse HBsAg-HQ assay detected HBsAg when HBV DNA was negative by the CTM assay. HBsAg was also detected by the Lumipulse HBsAg-HQ assay in 4 patients with an anti-HBs concentration of >10 mIU/ml, 3 of whom had no HBsAg escape mutations. The automatic, highly sensitive HBsAg CLEIA Lumipulse HBsAg-HQ is a convenient and precise assay for HBV monitoring.
Identification of Mycobacterium Species and Mycobacterium tuberculosis Complex Resistance Determinants by Use of PCR-Electrospray Ionization Mass Spectrometry
Authors: Simner Patricia J. , Buckwalter Seanne P. , Uhl James R. , Wengenack Nancy L. 
Published: August 2013

ABSTRACT

PCR coupled with electrospray ionization mass spectrometry (PCR–ESI-MS) is a novel technology that has recently been used to identify pathogens from clinical specimens or after culture within about 6 h. We evaluated the MDR-TB (multidrug-resistant tuberculosis) assay, which uses PCR–ESI-MS for detection and identification of
Mycobacterium
spp. and
Mycobacterium tuberculosis
complex (MTBC) resistance determinants from solid and broth Middlebrook culture media. The performance of the MDR-TB assay was compared to identification using nucleic acid hybridization probes and 16S rRNA gene sequencing for 68 MTBC and 97 nontuberculous mycobacterial (NTM) isolates grown on agar and 107 cultures grown in Bactec MGIT broth. MTBC resistance profiles from the MDR-TB assay were compared to results with the agar proportion method. The PCR–ESI-MS system correctly identified all MTBC isolates and 97.9% and 95.8% of the NTM isolates from characterized agar cultures and MGIT broth cultures to the species level, respectively. In comparison to the agar proportion method, the sensitivity and specificity for the detection of drug resistance using the MDR-TB assay were 100% and 92.3% for rifampin, 100% and 93.8% for isoniazid, 91.6% and 94.4% for ethambutol, and 100% and 100% for fluoroquinolones, respectively. The MDR-TB assay appears to be a rapid and accurate method for the simultaneous detection and identification of mycobacterial species and resistance determinants of MTBC from culture.
Evaluation of Rabies Biologics against Irkut Virus Isolated in China
Authors: Liu Ye , Chen Qi , Zhang Fei , Zhang Shoufeng , Li Nan , Lian Hai , Wang Ying , Zhang Jinxia , Hu Rongliang 
Published: August 2013

ABSTRACT

An Irkut virus (IRKV) was recently isolated from a bat in China. The protective ability of rabies biologics available in the Chinese market and experimental biologics against the rabies virus (RABV) and IRKV were assessed in a hamster model via preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) experiments. The results demonstrated that a single dose of rabies vaccine did not induce adequate protection against IRKV infection. However, routine PrEP with three doses of vaccine induced complete protection against IRKV infection. Higher doses of RABV immunoglobulins and alpha interferon were required during PEP to protect hamsters against IRKV versus RABV infection. Experimental recombinant vaccines containing IRKV glycoproteins induced more-reliable protection against IRKV than against RABV infection. Those findings may be explained by limited cross-neutralization of these viruses (confirmed via
in vitro
tests) in conjunction with antigenic distances between RABV and IRKV. These results indicate that the development and evaluation of new biologics for PrEP and PEP are required to ensure sufficient protection against IRKV infection in China and other territories where this virus is present.
Vaccination against a Virus-Encoded Cytokine Significantly Restricts Viral Challenge
Authors: Eberhardt Meghan K. , Deshpande Ashlesha , Chang W. L. William , Barthold Stephen W. , Walter Mark R. , Barry Peter A. 
Published: August 2013

ABSTRACT
Identification of immune correlates of protection for viral vaccines is complicated by multiple factors, but there is general consensus on the importance of antibodies that neutralize viral attachment to susceptible cells. Development of new viral vaccines has mostly followed this neutralizing antibody paradigm, but as a recent clinical trial of human cytomegalovirus (HCMV) vaccination demonstrated, this singular approach can yield limited protective efficacy. Since HCMV devotes >50% of its coding capacity to proteins that modulate host immunity, it is hypothesized that expansion of vaccine targets to include this part of the viral proteome will disrupt viral natural history. HCMV and rhesus cytomegalovirus (RhCMV) each encode an ortholog to the cellular interleukin-10 (cIL-10) cytokine: cmvIL-10 and rhcmvIL10, respectively. Despite extensive sequence divergence from their host's cIL-10, each viral IL-10 retains nearly identical functionality to cIL-10. Uninfected rhesus macaques were immunized with engineered, nonfunctional rhcmvIL-10 variants, which were constructed by site-directed mutagenesis to abolish binding to the cIL-10 receptor. Vaccinees developed antibodies that neutralized rhcmvIL-10 function with no cross-neutralization of cIL-10. Following subcutaneous RhCMV challenge, the vaccinees exhibited both reduced RhCMV replication locally at the inoculation site and systemically and significantly reduced RhCMV shedding in bodily fluids compared to controls. Attenuation of RhCMV infection by rhcmvIL-10 vaccination argues that neutralization of viral immunomodulation may be a new vaccine paradigm for HCMV by expanding potential vaccine targets.
Norovirus Genome Circularization and Efficient Replication Are Facilitated by Binding of PCBP2 and hnRNP A1
Authors: López-Manríquez Eduardo , Vashist Surender , Ureña Luis , Goodfellow Ian , Chavez Pedro , Mora-Heredia José Eduardo , Cancio-Lonches Clotilde , Garrido Efraín , Gutiérrez-Escolano Ana Lorena 
Published: August 2013

ABSTRACT
Sequences and structures within the terminal genomic regions of plus-strand RNA viruses are targets for the binding of host proteins that modulate functions such as translation, RNA replication, and encapsidation. Using murine norovirus 1 (MNV-1), we describe the presence of long-range RNA-RNA interactions that were stabilized by cellular proteins. The proteins potentially responsible for the stabilization were selected based on their ability to bind the MNV-1 genome and/or having been reported to be involved in the stabilization of RNA-RNA interactions. Cell extracts were preincubated with antibodies against the selected proteins and used for coprecipitation reactions. Extracts treated with antibodies to poly(C) binding protein 2 (PCBP2) and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 significantly reduced the 5′-3′ interaction. Both PCBP2 and hnRNP A1 recombinant proteins stabilized the 5′-3′ interactions and formed ribonucleoprotein complexes with the 5′ and 3′ ends of the MNV-1 genomic RNA. Mutations within the 3′ complementary sequences (CS) that disrupt the 5′-3′-end interactions resulted in a significant reduction of the viral titer, suggesting that the integrity of the 3′-end sequence and/or the lack of complementarity with the 5′ end is important for efficient virus replication. Small interfering RNA-mediated knockdown of PCBP2 or hnRNP A1 resulted in a reduction in virus yield, confirming a role for the observed interactions in efficient viral replication. PCBP2 and hnRNP A1 induced the circularization of MNV-1 RNA, as revealed by electron microscopy. This study provides evidence that PCBP2 and hnRNP A1 bind to the 5′ and 3′ ends of the MNV-1 viral RNA and contribute to RNA circularization, playing a role in the virus life cycle.
The effect of training doctors in communication skills on women’s satisfaction with doctor–woman relationship during labour and delivery: a stepped wedge cluster randomised trial in Damascus
Authors: Bashour Hyam N , Kanaan Mona , Kharouf Mayada H , Abdulsalam Asmaa A , Tabbaa Mohammed A , Cheikha Salah A 
Published: August 2013

ObjectivesTo determine the effect of training residents in interpersonal and communication skills on women’s satisfaction with doctor–woman relationship in labour and delivery rooms.DesignA stepped wedge cluster randomised trial.Setting4 tertiary care teaching maternity hospitals in Damascus, Syria.Participants2000 women who gave birth to a living baby in the four study hospitals and consented to participate in the intervention took part in the study. Women with difficult labour and high-risk pregnancies were excluded. All were interviewed at home after discharge.InterventionsA specially designed training package in communication skills was delivered to all resident doctors at the four hospitals.Primary outcome measuresThe main outcome measure was women’s satisfaction with interpersonal relationships in labour and delivery rooms measured via a series of questions on a Likert scale modified from the Medical Interview Satisfaction Scale.ResultsAt the individual level, the mean for the average satisfaction score was 3.23 (SD 0.72) of a possible score of 5 in the control group and 3.42 (SD 0.73) in the intervention group. Using generalised linear mixed models, we were unable to detect a difference between the mean for the average satisfaction score of women in the intervention arm and that of women in the control arm; the 95% CI associated with the effect of the intervention ranged from –0.08 to 0.15.ConclusionsDespite slight changes in the observed residents’ communication skills, the training package in communication skills does not seem to be associated with higher satisfaction scores of women. This raises the question of whether training individuals without further structural changes in the delivery of care and without further reinforcement of the training can have an impact on improving the quality of doctor–patient communication.Trial Registration NumberISRCTN80243969
069 Facilitating Implementation of Guidelines for the Prevention of Vascular Disease In General Practice
Authors: Harris M , Litt J , Russell G , Mazza D , Lloyd J , Zwar N , Taylor R , Driel M Van , Mar C Del , Krastev Y , Parker S , Smith J 
Published: August 2013

BackgroundAlthough evidence based guidelines have been developed and disseminated, up to a half of patients do not receive guideline based preventive care.ObjectivesThis study aims to evaluate a model for the implementation of preventive care guidelines in general practice.MethodsFollowing a development process for the intervention involving a mixed method study and a pilot carried out in three practices a cluster randomised controlled trial is being conducted in 31 practices across four states. The intervention involves training, preventive care audit, and visits from a facilitator based in the local primary care support organisation. The facilitator assists practices to review their clinical audit and implement a practice plan structured around the 5As to improve the reach and quality of preventive care. Quantitative and qualitative evaluation methods are being used to assess impact on planned change within the practice, recalled and recorded preventive care, and patient behaviours and risk factors for cardiovascular disease.ResultsBaseline data collection has been completed from practice staff and patients and the intervention is now complete. The recorded and patient recalled preventive care varied within and between practices resulting in a varied set of priorities for improvement. Early findings suggest that facilitation visits to review and plan improvements to the implementation of preventive guidelines are feasible, acceptable and can support organisational strategies to address gaps in care.DiscussionOur results may provide a model for local primary care support organisations to assist practices to improve their quality of preventive care.
074 Implementation of Grade Methodology in Recommendation Development
Authors: Haynes J , Regidor D , Chan W 
Published: August 2013

BackgroundWe have been developing CPGs for use within our organisation since 2002. Our lengthy, text- based rationales were not widely read by guideline users. We created a decision support (rationale) table, based on GRADE methodology, and added a summary statement (basis of recommendation) to allow readers a concise and transparent snapshot of our justification for recommendation and strength.ContextThe rationale serves as a bridge between systematic review and recommendation, and provides users with a high-level justification for a recommendation. The basis of recommendation (BoR) summarises the 4 GRADE domains of strength of recommendation and how they are integrated to derive the final recommendation and strength. The BoR serves to: •Provide information to the Guideline Development Team and frontline clinicians to facilitate discussion, consensus and aid clinical decision-making. •Provide a structured, standardised portal into more detailed information in the CPG.Description of Best PracticeWe follow GRADE’s 2-level designation of recommendation strength (strong/weak), and developed standardised recommendation language to align with recommendation strength. We considered two approaches to derive the final recommendation strength, finally settling on an approach that allows flexible weighting of the contribution of each domain to recommendation strength. With this approach, in special circumstances, a strong recommendation may be given in the absence of a high-level of certainty. We plan to provide direct links from the CPG to our electronic medical record’s decision support tools.Lessons for Guideline Developers, Adaptors, Implementers, and/or UsersA concise and targeted rationale helps clinicians understand how evidence is used to develop clinical practice recommendations.
075 The Use of GRADE Methods in the World Health Organization (Who) Public Health Guidelines (PHG): Distribution of Strength of Recommendations and Confidence in Estimates of Effect
Authors: Elias P , Norris S , Brito J , Stoltzfus R , Bero L , Djulbegovic B , Neumann I , Montiori V , Guyatt G 
Published: August 2013

BackgroundA perception exists that expert guideline panellists are sometimes reluctant to offer weak/conditional/contingent recommendations. GRADE guidance warns against strong recommendations when confidence in estimates of effect is low or very low (low or very low quality evidence), suggesting that such recommendations may seldom be justified.ObjectivesTo characterise the distribution of strength of recommendations and confidence in estimates of effect in WHO guidelines that have used the GRADE approach and graded strength of recommendations and confidence in effect estimates.MethodsWe reviewed guidelines listed in the WHO guidelines database as of November 2012. We identified those that use GRADE and, in these guidelines, examined the distributions of strong and weak and associated confidence in estimates of effect (high, moderate, low, and very low).ResultsWe identified 116 WHO guidelines; 48 (41.3%) referred to GRADE methods, and 43 (37%) utilised GRADE and provided both a strength of recommendation and confidence in estimates grading. These 43 guidelines included 456 recommendations, of which 290 (63.6%) were strong and 166 (36.4%) were conditional/weak. Of the 290 strong recommendations, 97 (33.4%) were based on evidence warranting low confidence in estimates of effect and 63 (21.7%) on evidence warranting only very low confidence.DiscussionStrong recommendations based on low or very low confidence in effect estimates are very frequently made in WHO guidelines. Further study to determine the reasons for such recommendations is warranted.Implications for Guideline Developers/UsersGuideline authors should provide a clear, compelling rationale for any strong recommendations based on low confidence estimates.