bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double red blood cell donors with increased ferritin levels: a descriptive study
Authors: Delage Gilles , Grégoire Yves , Lebrun André 
Published: July 2015

BACKGROUNDOne of the measures proposed to mitigate iron loss in blood donors is monitoring of their ferritin levels. Occasionally, high ferritin levels are found in monitored donors. We report the results of the clinical and laboratory investigation of 80 double red blood cell (DRBC) donors with high ferritin levels.STUDY DESIGN AND METHODSAll DRBC donors’ ferritin levels were measured during each visit for a donation. Donors with high ferritin levels who agreed to participate underwent a clinical and laboratory evaluation.RESULTSA total of 165 of 2757 DRBC donors had at least one high ferritin level. Five were already known to suffer from hemochromatosis. A full investigation was available for 80 other donors. A total of 61 of 80 donors had normalized their ferritin level at the time of their laboratory evaluation. Only 16 donors had high serum iron levels, of whom four had increased saturation index. Genetic analysis gave the following results: C282Y homozygous, two; H63D homozygous, six; C282Y/HC3D double heterozygote, six; C282Y heterozygote, six; H63D heterozygote, 19; and no mutations, 39. None of the other laboratory investigations contributed data explaining the high ferritin levels observed.CONCLUSIONIn most donors with high ferritin levels, the phenomenon was transient, with normal ferritin levels found in follow‐up. Less than 10% of these donors had evidence of iron overload. Only eight were homozygous for mutations associated with hemochromatosis. An extensive laboratory investigation by the treating physician should only be recommended in donors with persistently high ferritin levels.
Quantification of biological variation in blood‐based therapy – a summary of a meta‐analysis to inform manufacturing in the clinic
Authors: Thurman‐Newell J. A. , Petzing J. N. , Williams D. J. 
Published: July 2015

Background and ObjectivesBiological raw materials, the basis for cellular therapies such as stem cells, have a significantly greater degree of complexity than their traditional pharmaceutical counterparts. This can be attributed to the inherent variation of its source – human beings. Currently, cell therapies are made in small, ad hoc batches, but larger scale production is a prerequisite to meeting future demand and will require a quality‐by‐design approach to manufacturing that will be designed around, or be robust to this variation. Quantification of variation will require understanding of the current baseline and stratification of its sources.Materials and MethodsHaematopoietic stem cell therapy was chosen as a case study to explore this variation, and a PRISMA‐guided (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) systematic meta‐analysis was carried out for a number of predetermined cell measurements.ResultsFrom this data set, it appears that the extent of variation in therapeutic dose (in terms of transplanted total nucleated cells and CD34+ cells per kilogram) for HSCT is between one and four orders of magnitude of the median.ConclusionsThis is tolerated under the practice of medicine but would be unmanageable from a biomanufacturing perspective and raises concerns about comparable levels of efficacy and treatment. A number of sources that will contribute towards this variation are also reported, as is the direction of travel for 4 greater clarity of the scale of this challenge.
Microfluidic PMMA‐based microarray sensor chip with imaging analysis for ABO and RhD blood group typing
Authors: Pipatpanukul C. , Amarit R. , Somboonkaew A. , Sutapun B. , Vongsakulyanon A. , Kitpoka P. , Srikhirin T. , Kunakorn M. 
Published: July 2015

Background and ObjectivesSolid phase microarrays have been described for use in blood typing; red blood cells (RBCs) captured on immobilized antibodies were detected using surface plasmon resonance or fluorescence. We present antibody microarray on Poly (methylmethacrylate) (PMMA) surface coupled with microfluidic system for ABO and RhD blood typing. After immobilized by antigen–antibody interaction, the RBCs were detected by image recognition.Materials and MethodsThe sensor surface was produced from grafted aminopropyltriethoxysilane (APTES) on photochemical modified PMMA surface by UV irradiation and subsequently reacted with glutaraldehyde cross‐linking. The amine group of monoclonal antibody of anti‐A, anti‐B and anti‐D was reacted with an aldehyde group on the glutaraldehyde modified surface, forming an imine linkage. RBCs were captured by the coated antibody via antigen–antibody interaction, and blood grouping was determined by microarray image cell counting.ResultsSuitable condition for RBC detection was 10% RBC concentration at 10 μl/min flow rate. This setting eliminated non‐specific RBC binding resulting in correct blood groups identification of all 136 samples tested. The platform showed good reproducibility with coefficient of variation of 2·17%, 3·62% and 2·51% for anti‐A, anti‐B and anti‐D respectively. The antibody‐coated surface can be stabilized by stabilizer coating and stored for long‐term use.ConclusionThe PMMA array chip demonstrated its good accuracy and precision in rapid blood group testing. For its high throughput, the method has potential for use in large blood donation centre.
Noninvasive device readouts validated by immunohistochemical analysis enable objective quantitative assessment of acute wound healing in human skin
Authors: Ud‐Din Sara , Greaves Nicholas S. , Sebastian Anil , Baguneid Mohamed , Bayat Ardeshir 
Published: July 2015

ABSTRACTObjective evaluation of cutaneous wounds through use of noninvasive devices has important implications for diagnosis, monitoring treatment efficacy, progression and may lead to development of improved theranostic treatment strategies. However, there is a lack of validation in the use of certain devices in wound repair, where objective measurements taken by noninvasive devices have been corroborated by immunohistochemical analysis. Thus, data from three acute wound‐healing studies in healthy volunteers using three noninvasive objective devices were further evaluated by immunohistochemistry. One hundred ten participants had 5‐mm diameter skin biopsies to their arms. Spectrophotometric intracutaneous analysis (SIAscopy), full‐field laser perfusion imaging, and three‐dimensional imaging provided quantitative measurements of melanin, hemoglobin, collagen, blood flow, and wound size; all of which were validated by immunohistochemistry. Full‐field laser perfusion imaging showed blood flow increased to D7 and decreased by 40% to D14. SIAscopy showed that hemoglobin increased to D7 and reduced to D14. CD31 analysis corroborated this by showing a 76% increase in blood vessel density to D7 and a reduction by 14% to D14. Three‐dimensional imaging showed that wound surface area reduced by 50% from day 7 to day 14. Alpha‐smooth muscle Actin (Alpha‐SMA) staining supported these trends by showing increased levels by 72% from D0 to D14 (corresponding to wound contraction). Collagen, measured by SIAscopy, decreased to D7 and increased to D14, which was validated by collagen III analysis. Additionally, collagen I increased by 14% from D0 to D14. SIAscopy measurements for melanin showed an increase at D7 and a slight reduction to D14, while melanogenesis increased by 46.7% from D0 to D14. These findings show the utility of noninvasive objective devices in the quantitative evaluation of wound‐healing parameters in human skin as corroborated by immunohistochemistry. This may contribute to the development of prognostic parameters for assessment of response to wound therapy.
Atlanta Streets Alive: A Movement Building a Culture of Health in an Urban Environment
Authors: Torres Andrea , Steward John , Strasser Sheryl , Lyn Rodney , Serna Rebecca , Stauber Christine 
Published: July 2015

Background:Open Streets are community-based programs that promote the use of public space for physical activity (PA), recreation and socialization by closing streets temporarily to motorized vehicles, allowing access to pedestrians. The city of Atlanta hosted its first Open Streets event, Atlanta Streets Alive (ASA), in May 2010. An evaluation of the first 5 ASA events from May 2010 to May 2012 was conducted. The purpose was to learn about the characteristics of ASA participants, the influence of the event on their PA, and perceptions of safety and neighborhood social capital.Methods:ASA’s evaluation had 2 components: participant counts and a participant survey. Characteristics of participation were compared among the 3 different events in which surveys were conducted using the Pearson χ2 test and F test as appropriate.Results:The estimated participation at ASA increased from nearly 3,500 (ASA 1 to 4) to 12,520 (ASA 5). The number of events increased to 3 per year for a total of 10 events until 2014. Overall, 19.4% of participants met the weekly PA recommendation during 1 event.Conclusions:The expanding diversity of routes, participants, and sponsorships highlights the potential promise such programming offers in terms of establishing an urban culture of health.
Inhibition of AAC(6′)-Ib-Mediated Resistance to Amikacin in Acinetobacter baumannii by an Antisense Peptide-Conjugated 2′,4′-Bridged Nucleic Acid-NC-DNA Hybrid Oligomer
Authors: Lopez Christina , Arivett Brock A. , Actis Luis A. , Tolmasky Marcelo E. 
Published: July 2015

ABSTRACT

Multiresistant
Acinetobacter baumannii
, a common etiologic agent of severe nosocomial infections in compromised hosts, usually harbors
aac(6
′
)-Ib.
This gene specifies resistance to amikacin and other aminoglycosides, seriously limiting the effectiveness of these antibiotics. An antisense oligodeoxynucleotide (ODN4) that binds to a duplicated sequence on the
aac(6
′
)-Ib
mRNA, one of the copies overlapping the initiation codon, efficiently inhibited translation
in vitro
. An isosequential nuclease-resistant hybrid oligomer composed of 2′,4′-bridged nucleic acid-NC (BNA
NC
) residues and deoxynucleotides (BNA
NC
-DNA) conjugated to the permeabilizing peptide (RXR)
4
XB (“X” and “B” stand for 6-aminohexanoic acid and β-alanine, respectively) (CPPBD4) inhibited translation
in vitro
at the same levels observed in testing ODN4. Furthermore, CPPBD4 in combination with amikacin inhibited growth of a clinical
A. baumannii
strain harboring
aac(6
′
)-Ib
in liquid cultures, and when both compounds were used as combination therapy to treat infected
Galleria mellonella
organisms, survival was comparable to that seen with uninfected controls.
Lamellipodin Is Important for Cell-to-Cell Spread and Actin-Based Motility in Listeria monocytogenes
Authors: Wang Jiahui , King Jane E. , Goldrick Marie , Lowe Martin , Gertler Frank B. , Roberts Ian S. 
Published: July 2015

ABSTRACT

Listeria monocytogenes
is a foodborne pathogen capable of invading a broad range of cell types and replicating within the host cell cytoplasm. This paper describes the colocalization of host cell lamellipodin (Lpd) with intracellular
L. monocytogenes
detectable 6 h postinfection of epithelial cells. The association was mediated via interactions between both the peckstrin homology (PH) domain in Lpd and phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P
2
] on the bacterial surface and by interactions between the C-terminal EVH1 (Ena/VASP [vasodilator-stimulated phosphoprotein] homology domain 1) binding domains of Lpd and the host VASP (vasodilator-stimulated phosphoprotein) recruited to the bacterial cell surface by the listerial ActA protein. Depletion of Lpd by short interfering RNA (siRNA) resulted in reduced plaque size and number, indicating a role for Lpd in cell-to-cell spread. In contrast, overexpression of Lpd resulted in an increase in the number of
L. monocytogenes
-containing protrusions (listeriopods). Manipulation of the levels of Lpd within the cell also affected the intracellular velocity of
L. monocytogenes
, with a reduction in Lpd corresponding to an increase in intracellular velocity. These data, together with the observation that Lpd accumulated at the interface between the bacteria and the developing actin tail at the initiation of actin-based movement, indicate a possible role for Lpd in the actin-based movement and the cell-to-cell spread of
L. monocytogenes
.
Plasmodium falciparum Infection of Human Volunteers Activates Monocytes and CD16
+
Dendritic Cells and Induces Upregulation of CD16 and CD1c Expression
Authors: Teirlinck Anne C. , Roestenberg Meta , Bijker Else M. , Hoffman Stephen L. , Sauerwein Robert W. , Scholzen Anja 
Published: July 2015

ABSTRACT

Antigen-presenting cells (APCs) are key players in the induction and regulation of immune responses. In
Plasmodium falciparum
malaria, determination of which cells and pathways are activated in the network of APCs remains elusive. We therefore investigated the effects of a controlled human malaria infection in healthy, malaria-naive volunteers on the subset composition and activation status of dendritic cells (DCs) and monocytes. While subsets of monocytes increased in frequency during blood-stage infection, DC frequencies remained largely stable. Activation markers classically associated with peptide presentation to and priming of αβT cells, HLA-DR and CD86, were upregulated in monocytes and inflammatory CD16 myeloid DCs (mDCs) but not in the classical CD1c, BDCA2, or BDCA3 DC subsets. In addition, these activated APC subsets showed increased expression of CD1c, which is involved in glycolipid antigen presentation, and of the immune complex binding Fcγ receptor III (CD16). Our data show that
P. falciparum
asexual parasites do not activate classical DC subsets but instead activate mainly monocytes and inflammatory CD16 mDCs and appear to prime alternative activation pathways via induction of CD16 and/or CD1c. Changes in expression of these surface molecules might increase antigen capture and enhance glycolipid antigen presentation in addition to the classical major histocompatibility complex class II (MHC-II) peptide presentation and thereby contribute to the initiation of T-cell responses in malaria. (This study has been registered at Clinicaltrials.gov under registration no. NCT01086917.)
A Single Host-Derived Glycan Impacts Key Regulatory Nodes of Symbiont Metabolism in a Coevolved Mutualism
Authors: Pan Min , Schwartzman Julia A. , Dunn Anne K. , Lu Zuhong , Ruby Edward G. 
Published: July 2015

ABSTRACT

Most animal-microbe mutualistic associations are characterized by nutrient exchange between the partners. When the host provides the nutrients, it can gain the capacity to shape its microbial community, control the stability of the interaction, and promote its health and fitness. Using the bioluminescent squid-vibrio model, we demonstrate how a single host-derived glycan, chitin, regulates the metabolism of
Vibrio fischeri
at key points in the development and maintenance of the symbiosis. We first characterized the pathways for catabolism of chitin sugars by
V. fischeri
, demonstrating that the Ccr-dependent phosphoenolpyruvate-pyruvate phosphotransferase system (PTS) prioritizes transport of these sugars in
V. fischeri
by blocking the uptake of non-PTS carbohydrates, such as glycerol. Next, we found that PTS transport of chitin sugars into the bacterium shifted acetate homeostasis toward a net excretion of acetate and was sufficient to override an activation of the acetate switch by AinS-dependent quorum sensing. Finally, we showed that catabolism of chitin sugars decreases the rate of cell-specific oxygen consumption. Collectively, these three metabolic functions define a physiological shift that favors fermentative growth on chitin sugars and may support optimal symbiont luminescence, the functional basis of the squid-vibrio mutualism.

IMPORTANCE
Host-derived glycans have recently emerged as a link between symbiont nutrition and innate immune function. Unfortunately, the locations at which microbes typically access host-derived glycans are inaccessible to experimentation and imaging, and they take place in the context of diverse microbe-microbe interactions, creating a complex symbiotic ecology. Here we describe the metabolic state of a single microbial symbiont in a natural association with its coevolved host and, by doing so, infer key points at which a host-controlled tissue environment might regulate the physiological state of its symbionts. We show that the presence of a regulatory glycan is sufficient to shift symbiont carbohydrate catabolism, acetate homeostasis, and oxygen consumption.
Group Medical Visits (GMVs) in primary care: an RCT of group-based versus individual appointments to reduce HbA1c in older people
Authors: Khan Karim M , Windt Adriaan , Davis Jennifer C , Dawes Martin , Liu-Ambrose Teresa , Madden Ken , Marra Carlo A , Housden Laura , Hoppmann Christiane , Adams David J 
Published: July 2015

IntroductionType 2 diabetes mellitus (T2DM) affects more than 1.1 million Canadians aged ≥65 years. Group Medical Visits are an emerging health service delivery method. Recent systematic reviews show that they can significantly reduce glycated haemoglobin (HbA1c) levels, but Group Visits have not been evaluated within primary care. We intend to determine the clinical effectiveness, quality of life and economic implications of Group Medical Visits within a primary care setting for older people with T2DM.Methods and analysisA 2-year proof-of-concept, single-blinded (measurement team) randomised control trial to test the efficacy of Group Medical Visits in an urban Canadian primary care setting. Participants ≥65 years old with T2DM (N=128) will be equally randomised to either eight groups of eight patients each (Group Medical Visits; Intervention) or to Individual visits (Standard Care; Controls). Those administering cointerventions are not blinded to group assignment. Our sample size is based on estimates of variance (±1.4% for HbA1c) and effect size (0.9/1.4=0.6) from the literature and from our own preliminary data. Forty participants per group will provide a β likelihood of 0.80, assuming an α of 0.05. A conservative estimation of an effect size of 0.7/1.4 changes the N in the power calculation to 59 per group. Hence, we aim to enrol 64 participants in each study arm. We will use intention-to-treat analysis and compare mean HbA1c (% glycosylated HbA1c) (primary outcome) of Intervention/Control participants at 12 months, 24 months and 1 year postintervention on selected clinical, patient-rated and economic measures.Trial registration numberNCT02002143.
Non-medical use of prescription pain relievers among high school students in China: a multilevel analysis
Authors: Guo Lan , Xu Yan , Deng Jianxiong , He Yuan , Gao Xue , Li Pengsheng , Wu Hong , Zhou Jinhua , Lu Ciyong 
Published: July 2015

ObjectivesGiven the differences between general high school (GHS) and vocational high school (VHS) students, this study aimed to investigate the lifetime prevalence of non-medical use of prescription pain relievers (NMUPPR) among high school students as well as the associations between NMUPPR and individual-level factors and school category.MethodsA cross-sectional study was conducted in GHS and VHS students in 2012 in Chongqing, and 11 906 students’ questionnaires were completed and qualified for the survey. Self-reported NMUPPR and information regarding individual-level determinants and school category were collected. A multilevel multivariate logistic regression model was fitted to explore independent predictors of NMUPPR.ResultsThe total lifetime prevalence of NMUPPR was 11.3%, and NMUPPR was more prevalent among VHS students (15.8%) compared with GHS students (9.8%). Overall, the results indicated that VHS students were more likely to be involved in NMUPPR (adjusted OR (AOR)=1.64, 95% CI 1.42 to 1.89). Regarding the individual-level predictors of NMUPPR, below-average family economic status was negatively correlated with NMUPPR (AOR=0.77, 95% CI 0.60 to 0.98), and students with more pocket money were more likely to be engaged in NMUPPR. Students who had difficult family relationships, had poor relationships with teachers, had parents or friends who engaged in non-medical prescription drug use, and considered or attempted suicide were more likely to be engaged in NMUPPR.ConclusionsNMUPPR among high school students is a multidetermined phenomenon. The current findings indicate that VHS students are an important subgroup of adolescents and highlight the need for additional research as well as targeted prevention and intervention programmes for NMUPPR.
Failure mode and effects analysis: a comparison of two common risk prioritisation methods
Authors: McElroy Lisa M , Khorzad Rebeca , Nannicelli Anna P , Brown Alexandra R , Ladner Daniela P , Holl Jane L 
Published: July 2015

BackgroundFailure mode and effects analysis (FMEA) is a method of risk assessment increasingly used in healthcare over the past decade. The traditional method, however, can require substantial time and training resources. The goal of this study is to compare a simplified scoring method with the traditional scoring method to determine the degree of congruence in identifying high-risk failures.MethodsAn FMEA of the operating room (OR) to intensive care unit (ICU) handoff was conducted. Failures were scored and ranked using both the traditional risk priority number (RPN) and criticality-based method, and a simplified method, which designates failures as ‘high’, ‘medium’ or ‘low’ risk. The degree of congruence was determined by first identifying those failures determined to be critical by the traditional method (RPN≥300), and then calculating the per cent congruence with those failures designated critical by the simplified methods (high risk).ResultsIn total, 79 process failures among 37 individual steps in the OR to ICU handoff process were identified. The traditional method yielded Criticality Indices (CIs) ranging from 18 to 72 and RPNs ranging from 80 to 504. The simplified method ranked 11 failures as ‘low risk’, 30 as medium risk and 22 as high risk. The traditional method yielded 24 failures with an RPN ≥300, of which 22 were identified as high risk by the simplified method (92% agreement). The top 20% of CI (≥60) included 12 failures, of which six were designated as high risk by the simplified method (50% agreement).ConclusionsThese results suggest that the simplified method of scoring and ranking failures identified by an FMEA can be a useful tool for healthcare organisations with limited access to FMEA expertise. However, the simplified method does not result in the same degree of discrimination in the ranking of failures offered by the traditional method.
Best in show but not best shape: a photographic assessment of show dog body condition
Authors: Such Z. R. , German A. J. 
Published: July 2015

Previous studies suggest that owners often wrongly perceive overweight dogs to be in normal condition. The body shape of dogs attending shows might influence owners’ perceptions, with online images of overweight show winners having a negative effect. This was an observational in silico study of canine body condition. 14 obese‐prone breeds and 14 matched non‐obese‐probe breeds were first selected, and one operator then used an online search engine to identify 40 images, per breed, of dogs that had appeared at a major national UK show (Crufts). After images were anonymised and coded, a second observer subjectively assessed body condition, in a single sitting, using a previously validated method. Of 1120 photographs initially identified, 960 were suitable for assessing body condition, with all unsuitable images being from longhaired breeds. None of the dogs (0 per cent) were underweight, 708 (74 per cent) were in ideal condition and 252 (26 per cent) were overweight. Pugs, basset hounds and Labrador retrievers were most likely to be overweight, while standard poodles, Rhodesian ridgebacks, Hungarian vizslas and Dobermanns were least likely to be overweight. Given the proportion of show dogs from some breeds that are overweight, breed standards should be redefined to be consistent with a dog in optimal body condition.