bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting lentiviral vector to specific cell types through surface displayed single chain antibody and fusogenic molecule
Authors: Lei Yuning , Joo Kye-Il , Zarzar Jonathan , Wong Clement , Wang Pin 
Published: February 2010

Abstract

Background
Viral delivery remains one of the most commonly used techniques today in the field of gene therapy. However, one of the remaining hurdles is the off-targeting effect of viral delivery. To overcome this obstacle, we recently developed a method to incorporate an antibody and a fusogenic molecule (FM) as two distinct molecules into the lentiviral surface. In this report, we expand this strategy to utilize a single chain antibody (SCAb) for targeted transduction.

Results
Two versions of the SCAb were generated to pair with our various engineered FMs by linking the heavy chain and the light chain variable domains of the anti-CD20 antibody (αCD20) via a GS linker and fusing them to the hinge-CH2-CH3 region of human IgG. The resulting protein was fused to either a HLA-A2 transmembrane domain or a VSVG transmembrane domain for anchoring purpose. Lentiviral vectors generated with either version of the SCAb and a selected FM were then characterized for binding and fusion activities in CD20-expressing cells.

Conclusion
Certain combinations of the SCAb with various FMs could result in an increase in viral transduction. This two-molecule lentiviral vector system design allows for parallel optimization of the SCAb and FMs to improve targeted gene delivery.
The value of preoperative diagnostic tests in acute appendicitis, retrospective analysis of 196 patients
Authors: Memisoglu Kemal , Karip Bora , Mestan Metin , Onur Ender 
Published: February 2010

Abstract

Background
In this study our aim was to evaluate the diagnostic value of preoperative laboratory and radiological studies for appendicitis.

Methods
The clinical data of 196 patients who have undergone conventional appendectomy between March 2007 and April 2008 were collected retrospectively. Patients were examined for age, sex, white blood cell count, ultrasonography results, histopathological diagnosis and hospital stay.

Results
Negative appendectomy rate was 17.3% (27% for female, 11.5% for male). White blood cell counts were found to be high in 83% for acute appendicitis group and %61 for negative appendectomy group. There were 66 (34%) patients who had negative USG findings for acute appendicitis. Of these patients, histopathological examination revealed acute appendicitis in 46 patients whereas 20 patients had normal appendix. Hospital stays were 2.79 +/- 1.9 and 2.66 +/- 1.7 days for negative and positive appendicectomies respectively.

Conclusions
Besides the improvement of diagnostic tests for acute appendicitis, we could not sufficiently reduce the negative appendectomy rate.
The burden of acute respiratory infections in crisis-affected populations: a systematic review
Authors: Bellos Anna , Mulholland Kim , O'Brien Katherine L , Qazi Shamim A , Gayer Michelle , Checchi Francesco 
Published: February 2010

AbstractCrises due to armed conflict, forced displacement and natural disasters result in excess morbidity and mortality due to infectious diseases. Historically, acute respiratory infections (ARIs) have received relatively little attention in the humanitarian sector. We performed a systematic review to generate evidence on the burden of ARI in crises, and inform prioritisation of relief interventions. We identified 36 studies published since 1980 reporting data on the burden (incidence, prevalence, proportional morbidity or mortality, case-fatality, attributable mortality rate) of ARI, as defined by the International Classification of Diseases, version 10 and as diagnosed by a clinician, in populations who at the time of the study were affected by natural disasters, armed conflict, forced displacement, and nutritional emergencies. We described studies and stratified data by age group, but did not do pooled analyses due to heterogeneity in case definitions. The published evidence, mainly from refugee camps and surveillance or patient record review studies, suggests very high excess morbidity and mortality (20-35% proportional mortality) and case-fatality (up to 30-35%) due to ARI. However, ARI disease burden comparisons with non-crisis settings are difficult because of non-comparability of data. Better epidemiological studies with clearer case definitions are needed to provide the evidence base for priority setting and programme impact assessments. Humanitarian agencies should include ARI prevention and control among infants, children and adults as priority activities in crises. Improved data collection, case management and vaccine strategies will help to reduce disease burden.
Adenocarcinoma arising in a heterotopic pancreas (Heinrich type III): a case report
Authors: Inoue Yoshihiro , Hayashi Michihiro , Arisaka Yoshifumi , Higuchi Kazuhide , Egashira Yutaro , Tanigawa Nobuhiko 
Published: February 2010

Abstract

Introduction
Heterotopic pancreatic cancer in the duodenum is a very rare disease. Only twelve cases have been reported worldwide to date. We report a rare case of malignant transformation of heterotopic pancreas (Heinrich type III) in the duodenum with long-term survival of the patient, and review the 12 cases in the literature.

Case presentation
A 75-year-old Japanese man was admitted to our hospital complaining of nausea and vomiting. Endoscopy and upper gastrointestinal contrast study showed marked duodenal stenosis. A pylorus-preserving pancreaticoduodenectomy was performed. Histopathological examination of the surgically resected specimen showed malignant transformation of heterotopic pancreas (Heinrich type III) in the duodenum. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 30. He is well and shows no signs of recurrence at the time of writing, six years after the surgery.

Conclusion
Adenocarcinoma arising within the heterotopic pancreas appears to be rare. It is difficult to obtain a correct diagnosis preoperatively. The management of heterotopic pancreas depends on the presence or absence of symptoms. If the patient is asymptomatic or benign, conservative treatment with regular follow-up is recommended. When the patient is symptomatic or there is a suspicion of malignancy, surgical management with intra-operative frozen section diagnosis is indicated.
Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes
Authors: Minogue Ben M , Richardson Stephen M , Zeef Leo AH , Freemont Anthony J , Hoyland Judith A 
Published: February 2010

Abstract
Introduction
Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from AC and annulus fibrosus (AF) cells, and to further determine their expression in normal and degenerate human intervertebral disc (IVD) cells.

Methods
Microarrays were conducted on bovine AC, AF and NP cells, using Affymetrix Genechip® Bovine Genome Arrays. Differential expression levels for a number of genes were confirmed by quantitative real time polymerase chain reaction (qRT-PCR) on bovine, AC, AF and NP cells, as well as separated bovine NP and notochordal (NC) cells. Expression of these novel markers were further tested on normal human AC, AF and NP cells, and degenerate AF and NP cells.

Results
Microarray comparisons between NP/AC&AF and NP/AC identified 34 NP-specific and 49 IVD-specific genes respectively that were differentially expressed ≥100 fold. A subset of these were verified by qRT-PCR and shown to be expressed in bovine NC cells. Eleven genes (SNAP25, KRT8, KRT18, KRT19, CDH2, IBSP, VCAN, TNMD, BASP1, FOXF1 & FBLN1) were also differentially expressed in normal human NP cells, although to a lesser degree. Four genes (SNAP25, KRT8, KRT18 and CDH2) were significantly decreased in degenerate human NP cells, while three genes (VCAN, TNMD and BASP1) were significantly increased in degenerate human AF cells. The IVD negative marker FBLN1 was significantly increased in both degenerate human NP and AF cells.

Conclusions
This study has identified a number of novel genes that characterise the bovine and human NP and IVD transcriptional profiles, and allows for discrimination between AC, AF and NP cells. Furthermore, the similarity in expression profiles of the separated NP and NC cell populations suggests that these two cell types may be derived from a common lineage. Although interspecies variation, together with changes with IVD degeneration were noted, use of this gene expression signature will benefit tissue engineering studies where defining the NP phenotype is paramount.
High-density lipoproteins downregulate CCL2 production in human fibroblast-like synoviocytes stimulated by urate crystals
Authors: Scanu Anna , Oliviero Francesca , Gruaz Lyssia , Sfriso Paolo , Pozzuoli Assunta , Frezzato Federica , Agostini Carlo , Burger Danielle , Punzi Leonardo 
Published: February 2010

Abstract
Introduction
To investigate whether monosodium urate (MSU) crystals induce the production of CCL2 (monocyte chemoattractant protein-1; MCP-1) in human fibroblast-like synoviocytes (FLS) and whether this mechanism would be affected by high-density lipoproteins (HDL).

Methods
Human FLS isolated from synovial tissue explants were stimulated with MSU crystals (0.01 to 0.5 mg/ml) or interleukin (IL)-1β (10 pg/ml) in the presence or absence of HDL (50 and 100 μg/ml). The production and expression of CCL2 was evaluated with ELISA, confocal microscopy, immunofluorescence microscopy, chemotaxis assay, and real-time quantitative PCR.

Results
Exposure of FLS to MSU crystals induced CCL2 accumulation in culture medium in a dose- and time-dependent manner, reaching a plateau at 50 to 75 μg/ml MSU crystals and 20 to 24 hours. Although low, the induced CCL2 levels were sufficient to trigger mononuclear cell migration. In resting FLS, CCL2 was localized in small cytoplasmic vesicles whose number diminished with MSU crystal stimulation. Concomitantly, MSU crystals triggered the induction of CCL2 mRNA expression. All these processes were inhibited by HDL, which cause a 50% decrease in CCL2 mRNA levels and a dose-dependent inhibition of the release of CCL2. Similar results were obtained when FLS were pretreated with HDL and washed before activation by MSU crystals or IL-1β, suggesting a direct effect of HDL on the FLS activation state.

Conclusions
The present results demonstrate that MSU crystals induce FLS to release CCL2 that is stored in vesicles in resting conditions. This mechanism is inhibited by HDL, which may limit the inflammatory process by diminishing CCL2 production and, in turn, monocytes/macrophages recruitment in joints. This study confirms the antiinflammatory functions of HDL, which might play a part in the limitation of acute gout attack.
Local Decision-Makers Views' of National Guidance on Interventional Procedures in the Uk
Authors: Lourenco Tania , Grant Adrian , Burr Jennifer , Vale Luke 
Published: February 2010

Objectives To identify how decision-makers in the NHS perceive and manage interventional procedures guidance and to determine whether additional information would be useful. Methods Qualitative study using semi-structured interviews with seven providers, six commissioners and one policy-maker. The framework approach was used to analyse transcribed data, and emergent themes coded. Data were analysed separately for providers and commissioner organizations. Results Perceptions about how guidance is managed in provider organizations varied. Some decision-makers considered that guidance is handled very well whereas others think it is suboptimal and haphazard. It is unclear whether clinicians follow procedure for cautionary guidance. In commissioner organizations, guidance is not seen as a priority by most and is not considered an area that will soon enter routine clinical practice. Moreover, commissioners felt that guidance lacked relevance as there is no consideration of whether procedures are cost-effective or affordable. Despite this, respondents perceived that the content and quality of guidance is satisfactory. Useful additional information for inclusion in guidance would be: prevalence, incidence, cost, patients' views, consequences of using the new intervention, comparative information, effectiveness and cost-effectiveness. Conclusions Management of interventional procedures guidance in the NHS can be improved. It is important to understand the ways in which guidance meets and fails to meet decision-makers' needs.
HIV Testing of Health Care Workers in England - A Flawed Policy
Authors: Salkeld Lee , McGeehan Sarah 
Published: February 2010

A new Department of Health policy in England, published in 2007, recommended changes to the pre-employment health checks performed on health care workers before taking up their employment. The policy proposed that all new health care workers should receive immunization against TB and hepatitis B and should be offered testing for hepatitis C and HIV. It also advanced a new requirement that staff who perform exposure-prone procedures must be tested for TB, hepatitis B and C and HIV and must test negative for these diseases. Essentially mandatory HIV testing has been introduced for a large number of health care workers. The aim of the recommendations is to protect patients from contracting serious communicable diseases from health care professionals. Secondary objectives of the directive are to maintain confidence in the workforce and reduce the burden of patient notification exercises. This essay explores some of the shortcomings of this policy and examines the reasons why this policy will fail to meet its objectives. The justification for this new guidance is questioned and some of the ethical issues are highlighted.
Impact of Clinician Judgement on Formulary Committees’ Recommendations in Canada
Authors: Oremus Mark , Raina Parminder , Eva Kevin , Lavis John , Nair Kalpana , Lo Amanda , Smith Sarah 
Published: February 2010

Objectives In formulary committee deliberations, evidence for the efficacy of medications is often based on changes in the scale scores of patient-reported outcome measures. Our aim was to examine whether clinician judgement about the efficacy of medications for Alzheimer's disease, when added to scale score evidence, affects formulary committee members’ recommendations about providing these medications under public insurance. Methods The study was conducted using mixed methods. In a survey of formulary committee members in Canada, 32 participants were presented with scenarios that outlined different levels of efficacy for a medication. For each scenario, participants were asked to specify their likelihood of recommending that the medication be provided under public insurance. Of the 32 participants, 23 agreed to take part in an interview to explain the survey results. Content analysis was used to elicit recurrent themes across the interviews. Results When a medication was disease modifying, use of clinician judgement increased the mean likelihood of recommending that the medication be provided under public insurance. Despite this, some participants felt formulary committees should not use clinician judgement because of risks of subjectivity and bias. However, other participants believed the addition of clinician judgement would enhance the clinical relevance of evidence that might otherwise be based entirely on changes in scale score. Conclusions Clinician judgement about the efficacy of medications can influence formulary committee recommendations. This suggests the need for a new approach to govern the consideration of expert evidence during formulary committee deliberations.
Ciprofloxacin-Induced Hepatotoxicity Resolved with Levofloxacin: A Case Report and a Review of the Literature
Authors: Hirsch Adina C. , Lundquist Lisa M. 
Published: February 2010

Objective To report a case of elevated hepatic transaminases in a patient receiving ciprofloxacin that resolved upon discontinuation and initiation of levofloxacin. Summary A 45-year-old white woman was initiated on ciprofloxacin and gentamicin after a blood culture revealed gram-negative rods. On day 2 of antibiotic therapy, the patient's aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased to 2,352 units/L and 783 units/L, respectively, and remained elevated for the following 4 days. Baseline AST and ALT were within normal limits. On day 5 of therapy, ciprofloxacin was discontinued and levofloxacin was initiated. On the following day, the hepatic transaminases decreased (AST, 192 units/L; ALT, 582 units/L) and continued to normalize prior to hospital discharge. On a subsequent admission later in the month, levofloxacin was again administered for treatment of a gram-positive bacteremia, with no subsequent elevation of hepatic transaminases. Discussion An objective causality assessment revealed that the adverse drug reaction (ADR) was probable. Although reports of this ADR have been noted, there is no previously documented occurrence of resolution of elevated hepatic transaminases on therapeutic modification to another fluoroquinolone. Conclusion Ciprofloxacin may significantly elevate hepatic transaminases. The clinician should be aware of the unique ADR profiles of the different fluoroquinolones because hepatotoxicity may not be a class effect.
Prasugrel
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: February 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The January 2010 monograph topics are peramivir, pazopanib, ofatumumab, guanfacine extended-release tablets, and C1 esterase inhibitor (human). The DUE is on peramivir.
One-to-One Paraprofessionals for Students With Disabilities in Inclusive Classrooms: Is Conventional Wisdom Wrong?
Authors: Giangreco Michael F. 
Published: February 2010

AbstractAssigning one-to-one paraprofessionals has become an increasingly common response to support students with intellectual and other developmental disabilities in general education classrooms. This article challenges the conventional wisdom that such an approach to service provision is necessarily a desirable and supportive action. Five main reasons are presented that challenge overreliance on the use of one-to-one paraprofessionals in inclusive classrooms, establishing it as a critical issue in special education. A series of recommended positions and initial actions are offered to spur debate and encourage development of alternatives to the status quo.
“Why Not Have Fun?”: Peers Make Sense of an Inclusive High School Program
Authors: Naraian Srikala 
Published: February 2010

AbstractIncluding students with significant disabilities at the high school level has been a subject of increasing research in recent years. This study explores the experiences of a high school student with significant disabilities, Michael, through the narratives of his peers. Participant observation in the building indicated that Michael remained on the periphery of mainstream school experiences as his peers worked with an institutional narrative that was predicated on normative expectations of all students. Using data from interviews, the article investigates how Michael's peers made sense of the process of inclusion that was implemented within this building. It documents the practical constructions of students as they used various elements of the normative discourse within the building to fashion their own interpretations of significant disability. These candid student commentaries retained a persistent focus on the extent to which Michael's program addressed (or failed to address) his fun-loving disposition while remaining critical of the rationale behind the practices it supported. As the data showed, peers' notions of fun for Michael were deeply intertwined with the opportunities for participation made available to him and the critical necessity for social interaction with his peers.
Adult Female and Male Siblings of Persons With Disabilities: Findings From a National Survey
Authors: Hodapp Robert M. , Urbano Richard C. , Burke Meghan M. 
Published: February 2010

Abstract
In this study, the authors used a national, Web-based survey to examine female and male siblings of individuals with disabilities. More than 1,160 adult siblings completed a 163-question survey about themselves, their siblings, and their sibling relationships. Most respondents reported fairly close contact with their siblings and positive sibling relationships, good health, and benefits from being a sibling to a brother–sister with disabilities. Compared with men, women reported benefiting more from the sibling relationship. Relative to the U.S. population, female (though not male) siblings married later and divorced less often, and these women had their first child at later ages. Implications are discussed regarding future research and service needs.
Surface Diffusion Studies Using Neutron and Helium Spin-echo Spectroscopy
Authors: Fouquet Peter , Hedgeland Holly , Jardine Andrew P. 
Published: February 2010

Abstract
We review recent advances in neutron and helium spin-echo spectroscopy, applied to the diffusion of atoms and simple molecules adsorbed on surfaces. A comparative introduction to the techniques is given, including advances in theory and simulation techniques, followed by a summary of several recent sets of experimental results.
Concrete and Cement Paste Studied by Quasi-Elastic Neutron Scattering
Authors: Bordallo Heloisa N. , Aldridge Laurence P. 
Published: February 2010

Abstract
In a world where the effects of climate change on weather patterns is accepted as real and serious, the problem of decreasing the production of carbon dioxide is perceived as increasingly important. The cement industry produces 5–7% of the world’s carbon dioxide emission and its survival will depend on improvements in the production of concrete which will be both more durable and require less carbon dioxide per unit of manufacture than the currently produced concrete. The durability of concrete is related to its ability to limit fluid transmission and knowledge of how to reduce the rate at which water will be transmitted through cement paste is critical to improving durability. However, because of the complex chemical and physical nature of cement pastes, understanding water mobility is a great challenge. Many techniques are not applicable simply because they are not sensitive to the range of size from angstroms to microns and the extent of water interaction with the cement where water can either be chemically bound at hydroxyls or physically free in large pores. In this review paper, we present the most up to date results on the physical chemistry of the water/ cement paste interactions studied by quasi-elastic neutron scattering. These results bring new insight to the mobility of water in the gel pores, the small pores (radius less than 50Å) that control the rate of water transmission in the cement pastes from which high quality concrete will be made.