bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mother–Child Interaction as a Cradle of Theory of Mind: The Role of Maternal Emotional Availability
Authors: Licata Maria , Kristen Susanne , Sodian Beate 
Published: May 2015

AbstractThe present longitudinal study investigated the relative importance of emotional availability (EA) in 56 mother–child dyads when the child was 7 months and four‐year old as predictors of child's Theory of Mind at 4 years while controlling for early maternal mind‐mindedness (MM). Dyadic EA at 7 months predicted the child's Theory of Mind, even when controlling for child temperamental and cognitive characteristics as well as dyadic EA at 4 years and early maternal MM. Results indicate the specific importance of high emotional connectedness between mothers and infants for preschoolers' Theory of Mind development.
Bedside teaching: specialists versus non‐specialists
Authors: Woodley Niall , McKelvie Karen , Kellett Catherine 
Published: May 2015

SummaryBackgroundBedside teaching (BT) is a valuable learning experience for medical students. In 2010, the BT curriculum at the University of Dundee was revised so that clinical specialist doctors facilitated these sessions. The aim of this study was to compare student opinion of BT delivered by specialist and non‐specialist doctors.MethodsA retrospective survey was sent to two medical student year groups who received teaching delivered by either specialist or non‐specialist doctors during year 2.ResultsThe response rate was 24.5 per cent, of which 49.4 per cent were taught by specialists. Responses indicated that specialist doctors improved communication skills (p = 0.034), were less intimidating (p = 0.01) and gave greater opportunity to ask questions (p = 0.028) than their non‐specialist counterparts. Overall, students taught by specialty doctors rated BT as more valuable (p < 0.001). A positive correlation was noted between the frequency of patient interaction and the overall value of BT (p < 0.0121); however, there was no significant association between the main teaching location and the overall value of BT.DiscussionFindings indicate that specialist doctors provide students with a better understanding of disease processes. Several students from the specialist group noted that their tutors linked theory to practice. No significant difference was found between the two groups regarding whether teaching was at an appropriate level. Specialist doctors therefore allow a number of improvements over the use of non‐specialist doctors for BT.Overall, students taught by specialty doctors rated bedside teaching as more valuable
Interleukin‐6 enhances the activity of in vivo long‐term reconstituting hematopoietic stem cells in “hypoxic‐like” expansion cultures ex vivo
Authors: Duchez Pascale , Rodriguez Laura , Chevaleyre Jean , Lapostolle Veronique , Vlaski Marija , Brunet de la Grange Philippe , Ivanovic Zoran 
Published: May 2015

BACKGROUNDSince interleukin (IL)‐6 synergizes with the physiologically relevant O2 concentration in the maintenance of primitive hematopoietic stem cell (HSC) subpopulations, we hypothesized that its addition to our hypoxic response mimicking cultures (HRMCs), composed of an antioxidant‐supplied serum‐free xeno‐free medium supplemented with the cytokines stabilizing hypoxia‐inducible factor‐1α and balancing HSC self‐renewal and commitment, will result in a similar effect even if they are exposed to 20% O2.STUDY DESIGN AND METHODSHRMCs were exposed to 20 and 5% O2 with and without IL‐6. Functional committed progenitors (colony‐forming cells [CFCs]: CFU‐GM, BFU‐E, CFU‐Mix, and CFU‐Mk) were evaluated as well as the short‐ and long‐term repopulating HSCs using in vivo NSG mice model (primary and secondary recipients, respectively).RESULTSThe addition of IL‐6 to HRMCs exposed to 20% O2 did not significantly impact either the CFCs or in vivo short‐term repopulating cells. However, it enhanced both the frequency and the individual proliferative capacity of the most primitive long‐term repopulating cell population evidenced by the generation of human CFCs in the marrow of secondary recipient mice. The exposure of HRMCs to 5% O2 negatively affected the amplification of CFCs, which was not changed by the addition of IL‐6 and exhibited a partial enhancing effect on the long‐term repopulating cells.CONCLUSIONThe addition of IL‐6 to the cytokine cocktail further improves our expansion procedure based on atmospheric O2 concentration‐exposed HRMCs by enhancing the maintenance of the most primitive HSCs without a negative impact on the less primitive HSC populations and CFCs.
Bimodal distribution of Trypanosoma cruzi antibody levels in blood donors from a highly endemic area of Argentina: what is the significance of low‐reactive samples?
Authors: Remesar Mirta , Sabino Ester C. , del Pozo Ana , Mayer Allen , Busch Michael P. , Custer Brian 
Published: May 2015

BACKGROUNDLow‐level seroreactive donor samples that are inconsistently detected by different Trypanosoma cruzi immunoassays are common, but the population distribution has not been reported in an endemic region. The objective was to understand the distribution of low‐level reactive samples using highly sensitive immunoassays and the relationship with epidemiologic evidence of exposure to T. cruzi.STUDY DESIGN AND METHODSBlood donors (BDs) were recruited in two blood banks located in Chaco province, in northeastern Argentina, from June 2006 to March 2007. Donors completed a Chagas exposure questionnaire and provided blood samples. All samples were tested in parallel with five contemporary and commercially available enzyme immunoassays for T. cruzi and a subgroup by a chemiluminescent assay.RESULTSOf the 1423 enrolled donors, 304 (21.4%) tested positive on all assays while 93 (6.5%) were reactive on at least one assay (inconclusive). Epidemiologic evidence of exposure to T. cruzi was significantly higher among positive and inconclusive donors compared to seronegative BD (p values range from 0.01 to <0.001 depending on the exposure). Histograms of the signal‐to‐cutoff values from all positive samples showed clear bimodal distributions for the whole parasite lysate assays, but not for the one recombinant antigen‐based assay. Low antibody level responses were present in 30% to 40% of the reactives, depending on the assay.CONCLUSIONThe population of individuals exposed to T. cruzi in highly endemic regions has a bimodal distribution of antibody response to the parasite. Although the clinical significance of low‐level reactivity is not fully established, these results may reflect evolving seroreversions after spontaneously resolved infections.
Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria
Authors: Bassat Quique , Ogutu Bernhards , Djimde Abdoulaye , Stricker Kirstin , Hamed Kamal 
Published: May 2015

ABSTRACT

Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated
Plasmodium falciparum
malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.
RX-P873, a Novel Protein Synthesis Inhibitor, Accumulates in Human THP-1 Monocytes and Is Active against Intracellular Infections by Gram-Positive (Staphylococcus aureus) and Gram-Negative (Pseudomonas aeruginosa) Bacteria
Authors: Buyck Julien M. , Peyrusson Frédéric , Tulkens Paul M. , Van Bambeke Françoise 
Published: May 2015

ABSTRACT

The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by
Staphylococcus aureus
and
Pseudomonas aeruginosa
, using a pharmacodynamic approach allowing the determination of maximal relative efficacies (
E
max
values) and bacteriostatic concentrations (

C
s

values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter (
S. aureus
) and 2 to 8 mg/liter (
P. aeruginosa
), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains.
E
max
values (expressed as the decrease in the number of CFU from that in the initial inoculum) against
S. aureus
and
P. aeruginosa
reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h.

C
s

values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for
S. aureus
; ciprofloxacin and ceftazidime for
P. aeruginosa
). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against
P. aeruginosa
than against
S. aureus
. Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species.
Open-Label Study To Evaluate the Single-Dose Pharmacokinetics, Safety, and Tolerability of Doripenem in Infants Less than 12 Weeks in Chronological Age
Authors: Cirillo Iolanda , Vaccaro Nicole , Castaneda-Ruiz Bibiana , Redman Rebecca , Cossey Veerle , Bradley John S. , Allegaert Karel 
Published: May 2015

ABSTRACT

Doripenem, a parenteral carbapenem with broad-spectrum activity against aerobic Gram-negative and Gram-positive and anaerobic pathogens, is currently approved for use in adults in the United States and European Union. Single-dose doripenem pharmacokinetics in 52 infants <12 weeks in chronological age were investigated in this phase 1 study. Hospitalized, medically stable infants <12 weeks in chronological age were stratified into 6 groups based on chronological and gestational age designed to reflect increasing renal maturation and decreasing volume of distribution (
V

z

) for β-lactam antimicrobials during the first 3 months of life. Subjects received single-dose doripenem (5 mg/kg of body weight for <8 weeks and 8 mg/kg for ≥8 weeks in chronological age) administered intravenously over 1 h. Plasma samples were obtained immediately before the end of the infusion and 1.5, 3, and 7 h after the start of the infusion. Urine was obtained by indwelling catheter during the 8 h following infusion. Doripenem showed linear pharmacokinetics across the 6 age groups. Neonates (<4 weeks in chronological age) had increased mean exposure (area under the plasma concentration-time curve from time zero to infinite time [AUC
∞
], 45.7 versus 32.4 μg · h/ml), longer elimination half-life (2.98 versus 1.79 h), and lower clearance (2.03 versus 3.03 ml/min/kg) compared with infants >4 weeks. Mean
V

z

was highest in subjects with the earliest gestational age (<32 weeks): 0.564 liter/kg for neonates and 0.548 liter/kg for infants. Single-dose pharmacokinetics of doripenem administered as a 1-hour infusion in term and preterm infants <12 weeks in chronological age were similar to what has been observed in neonates and very young infants with other carbapenems. Single-dose doripenem was generally safe and well tolerated. (This study has been registered with ClinicalTrials.gov under registration no. NCT01381848 and with EudraCT under registration no. 2009-014387-20.)
Comparative Evaluation of Colistin Susceptibility Testing Methods among Carbapenem-Nonsusceptible Klebsiella pneumoniae and Acinetobacter baumannii Clinical Isolates
Authors: Dafopoulou Konstantina , Zarkotou Olympia , Dimitroulia Evangelia , Hadjichristodoulou Christos , Gennimata Vasiliki , Pournaras Spyros , Tsakris Athanasios 
Published: May 2015

ABSTRACT

We compared six colistin susceptibility testing (ST) methods on 61 carbapenem-nonsusceptible
Klebsiella pneumoniae
(
n
= 41) and
Acinetobacter baumannii
(
n
= 20) clinical isolates with provisionally elevated colistin MICs by routine ST. Colistin MICs were determined by broth microdilution (BMD), BMD with 0.002% polysorbate 80 (P80) (BMD-P80), agar dilution (AD), Etest, Vitek2, and MIC test strip (MTS). BMD was used as the reference method for comparison. The EUCAST-recommended susceptible and resistant breakpoints of ≤2 and >2 μg/ml, respectively, were applied for both
K. pneumoniae
and
A. baumannii
. The proportions of colistin-resistant strains were 95.1, 77, 96.7, 57.4, 65.6, and 98.4% by BMD, BMD-P80, AD, Etest, MTS, and Vitek2, respectively. The Etest and MTS methods produced excessive rates of very major errors (VMEs) (39.3 and 31.1%, respectively), while BMD-P80 produced 18% VMEs, AD produced 3.3% VMEs, and Vitek2 produced no VMEs. Major errors (MEs) were rather limited by all tested methods. These data show that gradient diffusion methods may lead to inappropriate colistin therapy. Clinical laboratories should consider the use of automated systems, such as Vitek2, or dilution methods for colistin ST.
IgG Antibodies to Endothelial Protein C Receptor-Binding Cysteine-Rich Interdomain Region Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 Are Acquired Early in Life in Individuals Exposed to Malaria
Authors: Turner Louise , Lavstsen Thomas , Mmbando Bruno P. , Wang Christian W. , Magistrado Pamela A. , Vestergaard Lasse S. , Ishengoma Deus S. , Minja Daniel T. R. , Lusingu John P. , Theander Thor G. 
Published: May 2015

ABSTRACT

Severe malaria syndromes are precipitated by
Plasmodium falciparum
parasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variant
P. falciparum
erythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of PfEMP1 proteins associated with severe malaria and found that the receptor for these PfEMP1 variants is endothelial protein C receptor (EPCR). The binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDR) of the subtypes α1.1 and α1.4 to α1.8. In this study, we investigated the acquisition of anti-CIDR antibodies using plasma samples collected in four study villages with different malaria transmission intensities in northeastern Tanzania during a period with a decline in malaria transmission. We show that individuals exposed to high levels of malaria transmission acquire antibodies to EPCR-binding CIDR domains early in life and that these antibodies are acquired more rapidly than antibodies to other CIDR domains. The rate by which antibodies to EPCR-binding CIDR domains are acquired in populations in areas where malaria is endemic is determined by the malaria transmission intensity, and on a population level, the antibodies are rapidly lost if transmission is interrupted. This indicates that sustained exposure is required to maintain the production of the antibodies.
Micropatterned Macrophage Analysis Reveals Global Cytoskeleton Constraints Induced by Bacillus anthracis Edema Toxin
Authors: Trescos Yannick , Tessier Emilie , Rougeaux Clémence , Goossens Pierre L. , Tournier Jean-Nicolas 
Published: May 2015

ABSTRACT

Bacillus anthracis
secretes the edema toxin (ET) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. The effects of ET on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. In this study, we have developed different adhesive micropatterned surfaces (L and crossbow) to control the shape of bone marrow-derived macrophages (BMDMs) and primary peritoneal macrophages. We found that macrophage F-actin cytoskeleton adopts a specific polar organization slightly different from classical human HeLa cells on the micropatterns. Moreover, ET induced a major quantitative reorganization of F-actin within 16 h with a collapse at the nonadhesive side of BMDMs along the nucleus. There was an increase in size and deformation into a kidney-like shape, followed by a decrease in size that correlates with a global cellular collapse. The collapse of F-actin was correlated with a release of focal adhesion on the patterns and decreased cell size. Finally, the cell nucleus was affected by actin reorganization. By using this technology, we could describe many previously unknown macrophage cellular dysfunctions induced by ET. This novel tool could be used to analyze more broadly the effects of toxins and other virulence factors that target the cytoskeleton.
HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase
Authors: Matamouros Susana , Hager Kyle R. , Miller Samuel I. 
Published: May 2015

ABSTRACT
HAMP domains are α-helical coiled coils that often transduce signals from extracytoplasmic sensing domains to cytoplasmic domains. Limited structural information has resulted in hypotheses that specific HAMP helix movement changes downstream enzymatic activity. These hypotheses were tested by mutagenesis and cysteine cross-linking analysis of the PhoQ histidine kinase, essential for resistance to antimicrobial peptides in a variety of enteric pathogens. These results support a mechanistic model in which periplasmic signals which induce an activation state generate a rotational movement accompanied by a tilt in α-helix 1 which activates kinase activity. Biochemical data and a high-confidence model of the PhoQ cytoplasmic domain indicate a possible physical interaction of the HAMP domain with the catalytic domain as necessary for kinase repression. These results support a model of PhoQ activation in which changes in the periplasmic domain lead to conformational movements in the HAMP domain helices which disrupt interaction between the HAMP and the catalytic domains, thus promoting increased kinase activity.

IMPORTANCE
Most studies on the HAMP domain signaling states have been performed with chemoreceptors or the HAMP domain of Af1503. Full-length structures of the HAMP-containing histidine kinases VicK and CpxA or a hybrid between the HAMP domain of Af1503 and the EnvZ histidine kinase agree with the parallel four-helix bundle structure identified in Af1503 and provide snapshots of structural conformations experienced by HAMP domains. We took advantage of the fact that we can easily regulate the activation state of PhoQ histidine kinase to study its HAMP domain in the context of the full-length protein in living cells and provide biochemical evidence for different conformational states experienced by
Salmonella enterica
serovar Typhimurium PhoQ HAMP domain upon signaling.
A Multiprotein DNA Translocation Complex Directs Intramycelial Plasmid Spreading during
Streptomyces
Conjugation
Authors: Thoma Lina , Dobrowinski Hyazinth , Finger Constanze , Guezguez Jamil , Linke Dirk , Sepulveda Edgardo , Muth Günther 
Published: May 2015

ABSTRACT

Conjugative DNA transfer in mycelial
Streptomyces
is a unique process involving the transfer of a double-stranded plasmid from the donor into the recipient and the subsequent spreading of the transferred plasmid within the recipient mycelium. This process is associated with growth retardation of the recipient and manifested by the formation of circular inhibition zones, named pocks. To characterize the unique
Streptomyces
DNA transfer machinery, we replaced each gene of the conjugative 12.1-kbp
Streptomyces venezuelae
plasmid pSVH1, with the exception of the
rep
gene required for plasmid replication, with a hexanucleotide sequence. Only deletion of
traB
, encoding the FtsK-like DNA translocase, affected efficiency of the transfer dramatically and abolished pock formation. Deletion of
spdB3
,
spd79
, or
spdB2
had a minor effect on transfer but prevented pock formation and intramycelial plasmid spreading. Biochemical characterization of the encoded proteins revealed that the GntR-type regulator TraR recognizes a specific sequence upstream of
spdB3
, while Orf108, SpdB2, and TraR bind to peptidoglycan. SpdB2 promoted spheroplast formation by T7 lysozyme and formed pores in artificial membranes. Bacterial two-hybrid analyses and chemical cross-linking revealed that most of the pSVH1-encoded proteins interacted with each other, suggesting a multiprotein DNA translocation complex of TraB and Spd proteins which directs intramycelial plasmid spreading.

IMPORTANCE
Mycelial soil bacteria of the genus
Streptomyces
evolved specific resistance genes as part of the biosynthetic gene clusters to protect themselves from their own antibiotic, making streptomycetes a huge natural reservoir of antibiotic resistance genes for dissemination by horizontal gene transfer.
Streptomyces
conjugation is a unique process, visible on agar plates with the mere eye by the formation of circular inhibition zones, called pocks. To understand the
Streptomyces
conjugative DNA transfer machinery, which does not involve a type IV secretion system (T4SS), we made a thorough investigation of almost all genes/proteins of the model plasmid pSVH1. We identified all genes involved in transfer and intramycelial plasmid spreading and showed that the FtsK-like DNA translocase TraB interacts with multiple plasmid-encoded proteins. Our results suggest the existence of a macromolecular DNA translocation complex that directs intramycelial plasmid spreading.
Softness of Sn isotopes in relativistic semiclassical approximation
Authors: Biswal S. K. , Singh S. K. , Patra S. K. 
Published: May 2015

Within the framework of relativistic Thomas–Fermi (RTF) and relativistic extended Thomas–Fermi (RETF) approximations, we calculate the giant monopole resonance (GMR) excitation energies for Sn and related nuclei. A large number of nonlinear relativistic force parameters are used in these calculations. We find a parameter set is capable to reproduce the experimental monopole energy of Sn isotopes, when its nuclear matter compressibility lies within 210–230 MeV, however, it fails to reproduce the GMR energy of other nuclei. That means, simultaneously a parameter set cannot reproduce the GMR values of Sn and other nuclei.