bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of platelet‐rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects
Authors: Chang Y‐C , Zhao J‐H 
Published: October 2011

AbstractBackground:  Platelet‐rich fibrin (PRF) by Choukroun’s technique is derived from an autogenous preparation of concentrated platelets. Little is known about the effects of PRF on periodontal ligament fibroblasts (PDLFs) and the application of PRF for periodontal regeneration.Methods:  PDLFs were derived from healthy individuals undergoing extraction for orthodontic reasons. Blood collection was carried out from healthy volunteers. PRF was obtained from a table centrifuge centrifuged at 3000 rpm for 12 minutes. The effects of PRF on PDLFs were determined by measuring the expression of phosphorylated extracellular signal‐regulated protein kinase (p‐ERK), osteoprotegerin (OPG) and alkaline phosphatase (ALP) activity. Moreover, we retrospectively examined the feasibility and safety of reconstructing the periodontal infrabony defects with PRF in six patients.Results:  PRF was found to increase ERK phosphorylation and OPG in PDLFs in a time‐dependent manner (p < 0.05). ALP activity was also significantly upregulated by PRF (p < 0.05). Application of PRF in infrabony defects exhibited pocket reduction and clinical attachment gain after six months. Periapical radiography revealed radiographic defect filled in grafted teeth.Conclusions:  The enhancement of p‐ERK, OPG and ALP expression by PRF may provide benefits for periodontal regeneration. Clinical and radiologic analysis showed that the use of PRF is an effective modality for periodontal infrabony defects.
How to engage experienced medicine users at the counter for a pharmacy-based asthma inhaler service
Authors: Kaae Susanne , Nørgaard Lotte Stig 
Published: October 2011

Abstract

Objectives
Recent studies have identified recruitment of customers at the pharmacy counter as a limiter to successful provision of cognitive services in community pharmacies especially that of experienced customers with refill prescriptions. The aim of the paper is to gain insight into current problems of recruiting.

Methods
A qualitative study was conducted based on semi-structured interviews with 12 participants in a project in 2010 aimed at optimising recruitment of experienced asthma patients for the Inhaler Technique Assessment Service in Denmark. An ad hoc analysis was applied in order to interpret pharmacy staff perceptions of experienced asthma patients in comparison with newly diagnosed patients and to categorise the types of developed recruitment strategies as to whether they reflected a technical or everyday-life perspective on medicine.

Key findings
Effective recruitment processes were found to follow a generic pattern which consisted of a special type of opening question followed by providing a justification for the service. The participants perceived that the main difference between experienced and newly diagnosed patients was their degree of knowledge about their condition or correct inhaler technique. Most questions, and especially those related to reasons for motivating the customer to accept the service, were dominated by a professional technical understanding of medicine. In particular, follow-up justification based on a life-world perspective needs to be developed further. The identified type of communication might prevent some customers from accepting the service as they are not motivated by technical arguments but rather by how their daily symptoms can be relieved.

Conclusions
Pharmacy staff should focus both on adequate opening questions as well follow-up justification when trying to recruit customers for cognitive services. The study might inform future studies on how to create new and more adequate strategies for recruitment of customers for relevant cognitive services in community pharmacies.
Evaluation of a multi staged professional development course for practising pharmacists in anticoagulation management
Authors: Bungard Tammy J , Schindel Theresa J , Garg Sipi , Brocklebank Cynthia 
Published: October 2011

Abstract

Background
With the evolution of pharmacist prescriptive authority in Alberta, Canada, professional development courses need to impact change in daily practice. We designed a multi stage course targeting anticoagulation management with several components: (1) a print-based course to develop foundational knowledge; (2) a 2-day workshop; (3) a 3-day experiential programme; (4) distance mentorship to practice site; and (5) two full-day mentorship meetings.

Objective
To assess the impact of a comprehensive anticoagulation professional development course on practising pharmacists' knowledge, confidence and daily practice, with documentation of resources for the mentorship phases.

Methods
A mixed method of evaluation using surveys to assess pharmacist knowledge and confidence and semi-structured interviews to assess the impact on practice. Surveys were conducted prior to and following the workshop, after the experiential training and 4–6 months following completion of the workshop. Interviews were conducted following the experiential training and 4–6 months after the workshop.

Results
Enrolment for the complete multi stage course was limited to 12 pharmacists, while another 59 completed the course to the end of the workshop. Pharmacists completing the entire course had improved knowledge scores following the workshop, and between the workshop and 3-day experiential. These scores declined at 4–6 months. Improvements in confidence occurred throughout the course. At the final interview, all pharmacists indicated a positive impact on their practice. Mentorship was feasible and imperative to offer security to facilitate practice change.

Conclusions
Overall, this comprehensive multi stage course improved knowledge, confidence and practice for pharmacists.
First Report of a Brain Abscess Caused by Nocardia veterana
Authors: Arends J. E. , Stemerding A. M. , Vorst S. P. , de Neeling A. J. , Weersink A. J. L. 
Published: October 2011

ABSTRACT

Among
Nocardia
species causing infections,
Nocardia veterana
is rarely isolated and is mostly described as causing pulmonary infections. This is the first presentation of a case of brain abscess attributable to an
N. veterana
infection in a patient with type 2 diabetes. Prolonged antibiotic therapy with trimethoprim-sulfamethoxazole led to successful clinical recovery.
IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States
Authors: Limbago Brandi M. , Rasheed J. Kamile , Anderson Karen F. , Zhu Wenming , Kitchel Brandon , Watz Nancy , Munro Susan , Gans Hayley , Banaei Niaz , Kallen Alex J. 
Published: October 2011

ABSTRACT

The emergence and spread of carbapenem-resistant
Enterobacteriaceae
(CRE) producing acquired carbapenemases have created a global public health crisis. In the United States, CRE producing the
Klebsiella pneumoniae
carbapenemase (KPC) are increasingly common and are endemic in some regions. Metallo-β-lactamase (MBL)-producing CRE have recently been reported in the United States among patients who received medical care in countries where such organisms are common. Here, we describe three carbapenem-resistant
K. pneumoniae
isolates recovered from pediatric patients at a single U.S. health care facility, none of whom had a history of international travel. The isolates were resistant to carbapenems but susceptible to aztreonam, trimethoprim-sulfamethoxazole, and fluoroquinolones. The three isolates were closely related to each other by pulsed-field gel electrophoresis and contained a common plasmid. PCR and sequence analysis confirmed that these isolates produce IMP-4, an MBL carbapenemase not previously published as present among
Enterobacteriaceae
in the United States.
Cholesterol Depletion of Hepatoma Cells Impairs Hepatitis B Virus Envelopment by Altering the Topology of the Large Envelope Protein
Authors: Dorobantu Cristina , Macovei Alina , Lazar Catalin , Dwek Raymond A. , Zitzmann Nicole , Branza-Nichita Norica 
Published: October 2011

ABSTRACT
Previous reports have shown that cholesterol depletion of the membrane envelope of the hepatitis B virus (HBV) impairs viral infection of target cells. A potential function of this lipid in later steps of the viral life cycle remained controversial, with secretion of virions and subviral particles (SVP) being either inhibited or not affected, depending on the experimental approach employed to decrease the intracellular cholesterol level. This work addressed the role of host cell cholesterol on HBV replication, assembly, and secretion, using an alternative method to inhibition of the enzymes involved in the biosynthesis pathway. Growing HBV-producing cells with lipoprotein-depleted serum (LPDS) resulted in an important reduction of the amount of cholesterol within 24 h of treatment (about 40%). Cell exposure to chlorpromazine, an inhibitor of the clathrin-mediated pathway used by the low-density lipoprotein receptor for endocytosis, also impacted the cholesterol level; however, this level of inhibition was not achievable when the synthesis inhibitor lovastatin was used. HBV secretion was significantly inhibited in cholesterol-depleted cells (by ∼80%), while SVP release remained unaffected. The viral DNA genome accumulated in LPDS-treated cells in a time-dependent manner. Specific immunoprecipitation of nucleocapsids and mature virions revealed an increased amount of naked nucleocapsids, while synthesis of the envelope proteins occurred as normally. Following analysis of the large envelope protein conformation in purified microsomes, we concluded that cholesterol is important in maintaining the dual topology of this polypeptide, which is critical for viral envelopment.
Determination of the psychometric properties of a behavioural marking system for obstetrical team training using high-fidelity simulation: Table 1
Authors: Morgan Pamela J , Tregunno Deborah , Pittini Richard , Tarshis Jordan , Regehr Glenn , Desousa Susan , Kurrek Matt , Milne Ken 
Published: October 2011

BackgroundTo determine the effectiveness of high-fidelity simulation for team training, a valid and reliable tool is required. This study investigated the internal consistency, inter-rater reliability and test–retest reliability of two newly developed tools to assess obstetrical team performance.MethodsAfter research ethics board approval, multidisciplinary obstetrical teams participated in three sessions separated by 5–9 months and managed four high-fidelity simulation scenarios. Two tools, an 18-item Assessment of Obstetric Team Performance (AOTP) and a six-item Global Assessment of Obstetric Team Performance (GAOTP) were used.5Eight reviewers rated the DVDs of all teams' performances.ResultsTwo AOTP items were consistently incomplete and omitted from the analyses. Cronbach's α for the 16-item AOTP was 0.96, and 0.91 for the six-item GAOTP. The eight-rater α for the GAOTP was 0.81 (single-rater intra-class correlation coefficient, 0.34) indicating acceptable inter-rater reliability. The ‘four-scenario’ α for the 12 teams was 0.79 for session 1, 0.88 for session 2, and 0.86 for session 3, suggesting that performance is not being strongly affected by the context specificity of the cases. Pearson's correlation of team performance scores for the four scenarios were 0.59, 0.35, 0.40 and 0.33, and for the total score across scenarios it was 0.47, indicating moderate test–retest reliability.ConclusionsThe results from this study indicate that the GAOTP would be a sufficient assessment tool for obstetrical team performance using simulation provided that it is used to assess teams with at least eight raters to ensure a sufficiently stable score. This could allow the quantitative evaluation of an educational intervention.
Three episodes of crustal development in the Rehoboth Province, Namibia
Authors: Van Schijndel Valby , Cornell David H. , Hoffmann K.-H. , Frei Dirk 
Published: October 2011

Abstract

The African continental crust was assembled by a series of orogenies over a period of billions of years mainly in Precambrian times. Tracing the build-up history of this stable crust is not always straightforward due to multiphase deformation and regions with poor outcrop. Episodes of metamorphism and magmatism associated with multiple Wilson cycles are recorded in zircons, which found their way into sediments derived from the hinterland. Dating of zircon populations in detrital rocks can hence provide age spectra which reflect the metamorphic and magmatic events of the region. Microbeam dating of detrital zircon is used to characterize the crustal development history of the Rehoboth Province of southern Africa. We investigated a quartzite of the Late Palaeo-Early Mesoproterozoic Billstein Formation, formed in a continental basin, and a quartz-feldspar arenite layer of the late Mesoproterozoic Langberg Formation conglomerates, immature sediments formed within a felsic volcanic system (both close to Rehoboth Town). The combined data indicate three episodes of crustal evolution in the Rehoboth Province. The oldest phase is only documented in the Billstein quartzite by three 2.98–2.7 Ga Archaean zircons. A Palaeoproterozoic phase between 2.2 and 1.9 Ga is older than any known exposures of the Rehoboth Province. The Billstein quartzite shows a main peak at 1.87 Ga, corresponding to the 1863±10 Ma Elim Formation. The Langberg sample reflects magmatism related to the entire Namaqua–Natal Wilson cycle between
c.
1.32 and 1.05 Ga. The absence of zircons of that age range in the Billstein quartzite indicates a pre-Namaqua age for the Billstein Formation. Our data shows that there were at least three episodes of crustal development at 2.98–2.7 Ga, 2.05–1.75 and 1.32–1.1 Ga. We have documented the existence of a previously unrecognized 2.98–2.7 Ga Archaean crustal component, which was probably exposed in the Rehoboth Province during the Palaeoproterozoic and thus indicates a much longer geological history for the Rehoboth Province than previously known.
Morphology, internal architecture and emplacement mechanisms of lava flows from the Central Atlantic Magmatic Province (CAMP) of Argana Basin (Morocco)
Authors: Hachimi Hind El , Youbi Nasrrddine , Madeira José , Bensalah Mohamed Khalil , Martins Línia , Mata João , Medina Fida , Bertrand Hervé , Marzoli Andrea , Munhá José , Bellieni Giuliano , Mahmoudi Abdelkader , Abbou Mohamed Ben , Assafar Hicham 
Published: October 2011

Abstract
The morphology, internal architecture and emplacement mechanisms of the Central Atlantic Magmatic Province (CAMP) lava flows of Argana Basin in Morocco are presented. The volcanic pile was produced by two volcanic pulses. The first, represented by the Tasguint Formation, corresponds to a succession of 3–13 individual flows created by 1–8 eruptions; the second, Alemzi Formation, is composed of 2–7 individual flows formed by 1–4 eruptions. These formations, geochemically distinct, are separated by thin silty or sandy horizons or by palaeosols. They include ‘compound pahoehoe flows’ and ‘simple flows’. The first type is almost exclusive of the lower formation, while the second type dominates the upper formation. The lava flows show clear evidence of endogenous growth or ‘inflation’. The characteristics of the volcanic pile suggest slow emplacement during sustained eruptive episodes and are compatible with a continental basaltic succession facies model.
Enhancement of TGF-β Signaling Responses by the E3 Ubiquitin Ligase Arkadia Provides Tumor Suppression in Colorectal Cancer
Authors: Sharma Vikas , Antonacopoulou Anna G. , Tanaka Shinya , Panoutsopoulos Alexios A. , Bravou Vasiliki , Kalofonos Haralabos P. , Episkopou Vasso 
Published: October 2011

Abstract
TGF-β signaling provides tumor protection against colorectal cancer (CRC). Mechanisms that support its tumor-suppressive properties remain unclear. The ubiquitin ligase Arkadia/RNF111 enhances TGF-β signaling responses by targeting repressors of the pathway for degradation. The corepressors SnoN/Ski, critical substrates of Arkadia, complex with the activated TGF-β signaling effectors Smad2/3 (pSmad2/3) on the promoters of target genes and block their transcription. Arkadia degrades this complex including pSmad2/3 and unblocks the promoter. Here, we report that Arkadia is expressed highly in the mouse colonic epithelium. Heterozygous Akd+/− mice are normal but express less Arkadia. This leads to reduced expression of several TGF-β target genes, suggesting that normal levels of Arkadia are required for efficient signaling responses. Critically, Akd+/− mice exhibit increased susceptibility to azoxymethane/dextran sodium sulfate carcinogen–induced CRC, as they develop four-fold more tumors than wild-type mice. Akd+/− tumors also exhibit a more aggressive pathology, higher proliferation index, and reduced cytostasis. Therefore, Arkadia functions as a tumor suppressor whose peak expression is required to suppress CRC development and progression. The accumulation of nuclear SnoN and pSmad2, along with the downregulation of TGF-β target genes observed in Akd+/− colon and tumors, suggest that tumor-suppressing properties of Arkadia are mediated by its ability to derepress TGF-β signaling. Consistent with this likelihood, we identified mutations in primary colorectal tumors from human patients that reduce Arkadia function and are associated with the accumulation of nuclear SNON. Collectively, our findings reveal that Arkadia enhances TGF-β signaling responses and supports its tumor-suppressing properties in CRC. Cancer Res; 71(20); 6438–49. ©2011 AACR.
EGFR Protein Expression in Non–Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor—A Novel Antibody for Immunohistochemistry or AQUA Technology
Authors: Mascaux Celine , Wynes Murry W. , Kato Yasufumi , Tran Cindy , Asuncion Bernadette Reyna , Zhao Jason M. , Gustavson Mark , Ranger-Moore Jim , Gaire Fabien , Matsubayashi Jun , Nagao Toshitaka , Yoshida Koichi , Ohira Tatuso , Ikeda Norihiko , Hirsch Fred R. 
Published: October 2011

Abstract
Introduction: Epidermal growth factor receptor (EGFR) protein expression in non–small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC).
Methods: Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared.
Results: EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy.
Conclusions: EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796–807. ©2011 AACR.
Phase I Trial of ALT-801, an Interleukin-2/T-Cell Receptor Fusion Protein Targeting p53 (aa264–272)/HLA-A*0201 Complex, in Patients with Advanced Malignancies
Authors: Fishman Mayer N. , Thompson John A. , Pennock Gregory K. , Gonzalez Rene , Diez Luz M. , Daud Adil I. , Weber Jeffery S. , Huang Bee Y. , Tang Shamay , Rhode Peter R. , Wong Hing C. 
Published: October 2011

Abstract
Purpose: ALT-801 is a bifunctional fusion protein comprising interleukin-2 (IL-2) linked to a soluble, single-chain T-cell receptor domain that recognizes a peptide epitope (aa264–272) of the human p53 antigen displayed on cancer cells in the context of HLA-A*0201 (p53+/HLA-A*0201). We evaluated the safety, pharmacokinetics, and pharmacodynamics of ALT-801 in p53+/HLA-A*0201 patients with metastatic malignancies.
Experimental Design: p53+/HLA-A*0201 patients were treated with ALT-801 on a schedule of four daily 15-minute intravenous infusions, then 10 days rest and four more daily infusions. Cohorts of patients were treated at 0.015, 0.040, and 0.080 mg/kg/dose.
Results: Four, 16, and 6 patients were treated at the 0.015, 0.04, and 0.08 mg/kg cohorts, respectively. Two dose-limiting toxicities (a grade 4 transient thrombocytopenia and a myocardial infarction) in the 0.08 mg/kg cohort established the maximum tolerated dose (MTD) at 0.04 mg/kg. Patients treated at the MTD experienced toxicities similar to those associated with high-dose IL-2 but of lesser severity. The serum half-life of ALT-801 was 4 hours and ALT-801 serum recovery was as expected based on the dose administered. ALT-801 treatment induced an increase of serum IFN-γ but not TNF-α. Response assessment showed 10 subjects with stable disease at at least 11 weeks, and in one who had melanoma metastasis, there is an ongoing complete absence of identifiable disease after resection of radiographically identified lesions.
Conclusion: This first-in-man study defines an ALT-801 regimen that can be administered safely and is associated with immunologic changes of potential antitumor relevance. Clin Cancer Res; 17(24); 7765–75. ©2011 AACR.
Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis
Authors: Ward Jennifer Ellis , Ren Ruiyi , Toraldo Gianluca , SooHoo Pam , Guan Jian , O'Hara Carl , Jasuja Ravi , Trinkaus-Randall Vickery , Liao Ronglih , Connors Lawreen H. , Seldin David C. 
Published: October 2011

AbstractSystemic AL amyloidosis results from the aggregation of an amyloidogenic immunoglobulin (Ig) light chain (LC) usually produced by a plasma cell clone in the bone marrow. AL is the most rapidly fatal of the systemic amyloidoses, as amyloid fibrils can rapidly accumulate in tissues including the heart, kidneys, autonomic or peripheral nervous systems, gastrointestinal tract, and liver. Chemotherapy is used to eradicate the cellular source of the amyloidogenic precursor. Currently, there are no therapies that target the process of LC aggregation, fibril formation, or organ damage. We developed transgenic mice expressing an amyloidogenic λ6 LC using the cytomegalovirus (CMV) promoter to circumvent the disruption of B cell development by premature expression of recombined LC. The CMV-λ6 transgenic mice develop neurologic dysfunction and Congophilic amyloid deposits in the stomach. Amyloid deposition was inhibited in vivo by the antibiotic doxycycline. In vitro studies demonstrated that doxycycline directly disrupted the formation of recombinant LC fibrils. Furthermore, treatment of ex vivo LC amyloid fibrils with doxycycline reduced the number of intact fibrils and led to the formation of large disordered aggregates. The CMV-λ6 transgenic model replicates the process of AL amyloidosis and is useful for testing the antifibril potential of orally available agents.