bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of a Community Health Center and Uninsured Emergency Department Visit Rates in Rural Counties
Authors: Rust George , Baltrus Peter , Ye Jiali , Daniels Elvan , Quarshie Alexander , Boumbulian Paul , Strothers Harry 
Published: December 2008

ABSTRACT:
Context: Community health centers (CHCs) provide essential access to a primary care medical home for the uninsured, especially in rural communities with no other primary care safety net. CHCs could potentially reduce uninsured emergency department (ED) visits in rural communities. Purpose: We compared uninsured ED visit rates between rural counties in Georgia that have a CHC clinic site and counties without a CHC presence. Methods: We analyzed data from 100% of ED visits occurring in 117 rural (non‐metropolitan statistical area [MSA]) counties in Georgia from 2003 to 2005. The counties were classified as having a CHC presence if a federally funded (Section 330) CHC had a primary care delivery site in that county throughout the study period. The main outcome measure was uninsured ED visit rates among the uninsured (all‐cause ED visits and visits for ambulatory care sensitive conditions). Poisson regression models were used to examine the relationship between ED rates and the presence of a CHC. To ensure that the effects were unique to the uninsured population, we ran similar analyses on insured ED visits. Findings: Counties without a CHC primary care clinic site had 33% higher rates of uninsured all‐cause ED visits per 10,000 uninsured population compared with non‐CHC counties (rate ratio [RR] 1.33, 95% confidence interval [CI] 1.11‐1.59). Higher ED visit rates remained significant (RR 1.21, 95% CI 1.02‐1.42) after adjustment for percentage of population below poverty level, percentage of black population, and number of hospitals. Uninsured ED visit rates were also higher for various categories of diagnoses, but remained statistically significant on multivariate analysis only for ambulatory care sensitive conditions (adjusted RR = 1.22, 95% CI 1.01‐1.47). No such relationship was found for ED visit rates of insured patients (RR 1.06, 95% CI 0.92‐1.22). Conclusions: The absence of a CHC is associated with a substantial excess in uninsured ED visits in rural counties, an excess not seen for ED visit rates among the insured.
Prospective cohort comparison of bioactive glass implants and conchal cartilage in reconstruction of the posterior canal wall during tympanomastoidectomy
Authors: Abramovich S. , Hannan S.A. , Huins C.T. , Georgalas C. , McGuinness J. , Vats A. , Thompson I. 
Published: December 2008

Objective:  To compare the effectiveness of bioactive glass implants and conchal cartilage in reconstructing the posterior canal wall during tympanomastoidectomy.Study design:  Prospective cohort clinical study.Setting:  Teaching hospital.Patients:  Patients with clinically diagnosed chronic suppurative otitis media and cholesteatoma awaiting tympanomastoidectomy were recruited.Intervention:  All patients underwent tympanomastoidectomy by the same surgeon. A first cohort of 12 patients underwent posterior canal wall reconstruction with autogenous conchal cartilage. A second cohort of 12 patients underwent such reconstruction with prefabricated bioactive glass.Main outcome measures:  Primary– All patients underwent out‐patient review at 1, 3, 6 and 12 months postoperatively, after which a second‐look procedure was performed. Reconstructions were inspected for evidence of epithelialization, granulation, infection, stenosis, depression and extrusion. Secondary– All patients had perioperative serial pure‐tone audiometry to check for any change in hearing levels upto 1 year postoperatively.Results:  By 1 year postoperatively, both reconstructive graft materials showed good epithelialization, no granulation, no infection, no ear canal stenosis, no depression and no extrusion. At operative second‐looks, bioactive glass particularly showed good tissue bonding, including both neovascularization and connective tissue integration. Overall clinical outcome was equivalent for both materials. Both graft materials showed no statistically significant difference in postoperative hearing levels.Conclusions:  Bioactive glass and conchal cartilage showed equivalent clinical outcome in reconstructing the posterior canal wall without significantly affecting hearing levels. As bioactive glass does not require second site morbidity and thus also reduces operative time, we prefer it for reconstructing the posterior canal wall following tympanomastoidectomy.
Altered expressions of trefoil peptides genes in squamous cell carcinoma of the larynx
Authors: Sipaul F. , Corfield A. , Wood S. , Upile T. , Sheffield E. , Birchall M.A. 
Published: December 2008

Aim.  Trefoil peptides (TFF) are secretory products of mucin‐producing cells and influence the rheological properties of mucous gels.1 They are thought to be important for the repair of mucosa damage.2 We hypothesised that TFF genes would be expressed in laryngeal mucosa and that this would be altered by smoking and neoplasia.Methods.  The expressions of TFF1‐3 were examined using 35S‐dATP in situ hybridisation. Biopsies were obtained from the supraglottic mucosa of non‐smokers (normal, n = 14) and smokers (smokers, n = 14) without laryngeal disease undergoing routine surgery and compared with tissue from archival squamous cell carcinoma (SCC: laryngectomy) specimens (n = 14). Autoradiographic intensity was scored (semi‐quantitatively) by two independent observers and compared to positive and negative control tissue.Results.  Scores are medians for each gene.

TFF gene
Normal (n = 14)
Smokers (n = 14)
SCC (n = 14)

TFF1
0
0
+

TFF2
0/+
0
+

TFF3
++
+
++

Expression was scored as 0–+++; 0 = absent, +++ strongly positive.

Discussion.  Major expression of TFF3 and weak expression of TFF2 are found in normal laryngeal mucosa. TFF3 appears to be down‐regulated in smokers and then up‐regulated again in the cancer group (SCC). The significant findings are that TFF1 and 2 appear to be expressed or up‐regulated in the cancer group. These findings suggest that laryngeal squamous cell carcinogenesis is associated with abnormal TFF1 and TFF2 genes expressions.References.  1 Kutta H., Steven P., Varoga D. et al. (2004) TFF peptides in the human false vocal folds of the larynx. Peptides. 25(5), 811–8182 Taupin D. & Podolsky D.K. (2003) Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol. 4(9), 721–732
The use of Nutlin‐3 as a radiosensitiser in laryngeal carcinoma cells harbouring wild‐type p53
Authors: Arya A.K. , Devlin T. , El‐Fert A. , Banfield M. , Rubbi C. , Lloyd B. , Fenwick J. , Jones T.M. , Boyd M.T. 
Published: December 2008

Objectives.  Radiotherapy is one of the mainstays of treatment for squamous cell carcinoma of the larynx but is often associated with severe morbidity. Providing patients with targeted treatment according to tumour type is a major goal of clinicians treating the disease. It has previously been shown that p53 is a critical mediator of radiation response and thus we investigated its influence on radiosensitivity and also whether Nutlin‐3 (the small molecule inhibitor of p53/MDM2 interaction) could radiosensitise tumours.Methods.  Seven cell lines derived exclusively from patients with laryngeal carcinoma and with defined p53 status (determined by direct sequencing of exons 2–11 and intron/exon boundaries) were examined. Radiosensitivity was determined by clonogenic assays following treatment with gamma irradiation in the presence and absence of Nutlin‐3. Flow cytometry was used to determine cell cycle characteristics and the levels of apoptosis and senescence were also measured.Results.  Cells with p53 homozygous mutations were relatively radiosensitive (SF2 < 20%). Cell lines with wild‐type p53, heterozygous and homozygous non‐sense mutations were relatively radioresistant (SF2 > 60%). Wild‐type p53 cells were made significantly more radiosensitive after treatment with Nutlin‐3. Neither apoptosis nor cell cycle responses corresponded with radiosensitivity. Interestingly, cells that displayed senescence were radioresistant whereas those that did not were radiosensitive suggesting a possible role for senescence in determining radiosensitivity.Conclusions.  This is the first study to demonstrate that Nutlin‐3 may be an effective radiosensitiser in laryngeal cancer cell lines with wild‐type p53. The clinical application of Nutlin‐3 might improve survival rates or reduce therapeutic doses in these patients.
Proteomic analysis of metastatic laryngeal squamous cell carcinoma
Authors: Goodyear P.W.A. , Boyd M.T. , Jenkins R. , Hamlett J. , Kitteringham N. , Jones T.M. 
Published: December 2008

Objectives.  Patients presenting with head and neck cancer may have no clinical or radiological evidence of cervical lymph node metastasis – the N0 neck. Despite this, histo‐pathological data has confirmed the presence of occult metastases in up to 30% of N0 necks (i.e. N+), depending on the site of the primary tumour. Currently there is no way of identifying affected individuals and consequently, 70% may be overtreated.1 Using proteomic and immuno‐histochemical (IHC) techniques, we attempted to identify a primary tumour phenotype, which would allow the discrimination of laryngeal squamous cell carcinoma (LSCC) with metastatic potential.Method.  Six fresh frozen primary LSCC samples; three each from patients with a histopathologically confirmed N+ or N0 neck were used. Following homogenisation of the tumour tissue, protein separation using 2D gel electrophoresis was performed. Differences in individual protein expression between N0 and N+ groups were identified using Progenesis SameSpots® gel analysis software. Differentially expressed proteins were extracted from the gels and identification was achieved using a combination of matrix‐assisted laser desorption and ionization mass spectrometry (MS) (MALDI) and liquid chromatography tandem MS (LC‐MS/MS).Results.  Ten strongly differentially expressed proteins were identified. Those identified included heat shock protein 90, T complex protein 1 gamma, Bromodomain PHD finger protein 3 and lactate dehyrogenase A, which were up‐regulated and thymidine phosphorylase which was down‐regulated in N+ samples.Conclusions.  These proteins represent potential biomarkers of metastatic potential in LSCC. Further investigation of their worth as biomarkers is necessary using, in the first instance, large sample tissue microarrays.Reference. 1 Yarbrough W.G., Slebos R.J.C. & Liebler D. (2006) Proteomics: clinical applications for head and neck squamous cell carcinoma. Head Neck. 28, 549–558
Raised EGFR in combination with low cyclin D1 is associated with radioresistance in laryngeal carcinoma cells
Authors: Banfield M.C. , Arya A.K. , Behrendt A. , El‐Fert A. , Devlin T. , Rubbi C. , Munir N. , Boyd M.T. , Jones T.M. 
Published: December 2008

Introduction.  Radiotherapy is one of the mainstays of treatment for squamous cell carcinoma. Identifying tumour markers able to predict tumour sensitivity to radiotherapy could enable patient/tumour specific treatment targeting and/or dose modification. In a recent study we demonstrated that high levels of EGFR and cyclin D1 were associated with disease recurrence after radiotherapy for patients with T2 laryngeal cancer.1 The aim of this study was to investigate this relationship in a panel of cell lines derived from laryngeal squamous cell carcinomas (LSCC).Methods.  Six LSCC cell lines were exposed to 2Gy of gamma irradiation from a 147Caesium source. Following irradiation, a clonogenic assay was used to define the relative radiosensitivity (SF2) of each cell line. Western blot analysis, followed by densitometry measurement, was used to determine the relative expression of EGFR and cyclin D1 in each cell line.Results.  Levels of EGFR and cyclin D1 were individually not strongly predictive for radiosensitivity. However, cell lines with a combination of high expression of EGFR and low expression of cyclin D1 were found to correlate strongly with a radioresistant phenotype (P = 0.95).Conclusions.  This study accords with previous evidence that the cyclin D1/ EGFR axis is important in determining radiation susceptibility. However, in contrast to previous work we found that low, as opposed to high levels of cyclin D1, were associated with radioresistance. Our studies provide an opportunity for functional investigation of the roles of EGFR and cyclin D1 in determining radioresistance in LSCC cells.
The effect of macrolides on allergic rhinitis versus chronic rhinosinusitis – An in vitro study
Authors: Kuchai R. , Wedzicha W. , Alusi G. 
Published: December 2008

Objectives.  The aims of this study were to explore the differences in the pathophysiological mechanisms of allergic rhinitis and chronic rhinosinusitis and their interactions with macrolides. The first hypothesis is that there are fundamental differences in the process that results in allergic rhinitis and chronic rhinosinusitis. These differences were investigated by analysing baseline levels of cytokine and subsequent effects of bacterial endotoxin on human nasal epithelial cells (HNECs) within three patient subgroups:‐Normal (non‐atopic); allergic rhinitics and chronic rhinosinusitics. The second hypothesis is that there is a difference in the cytokine responses mounted by macrolides in allergic rhinitis, chronic rhinosinusitis. A comparative study of cytokine reactivity in these three groups has not previously been undertaken.Method.  Human nasal epithelial cells were grown from nasal turbinate biopsy as explant cultures. Nasal tissue was obtained from three groups of patients:‐ (1). Normal, non‐atopics (2). Allergic rhinitics (AR) (3). Chronic rhinosinusitics(CRS). The HNECs were stimulated by LPS endotoxin and then exposed to macrolides.Results.  Erythromycin significantly reduced IL‐6 and IL‐8 levels (P < 0.05) in allergic rhinitics as well as unstimulated CRS. LPS had no significant effect on stimulated CRS however significantly reduced IL‐6 and IL‐8 in unstimulated cells. Erythromycin may either inhibit the expression or release of these inflammatory mediators.Conclusions.  The results help formulate an improved understanding of potential anti‐inflammatory effects and thereby potential applications in the management of both allergic rhinitis and chronic rhinosinosinusitis. The anti‐inflammatory effects of erythromycin require further in vivo analysis.
Effect of Oxygen Concentration on Photo‐oxidation and Photosensitizer Bleaching in Butter
Authors: Wold Jens Petter , Veberg Dahl Annette , Lundby Frank , Nilsen Asgeir Nikolai , Juzeniene Asta , Moan Johan 
Published: December 2008

AbstractThe effect of headspace oxygen concentration and color of light on photo‐oxidation and degradation of photosensitizers in butter was studied. Butter samples were stored under 0%, 0.4%, 0.8%, 1.6%, 3.0%, 5.0%, 21% oxygen, and exposed to violet, green or red light. Storage time was 36 h. Degree of photo‐oxidation was measured by a trained sensory panel. Photobleaching of six different photosensitizers was estimated based on front face fluorescence excitation and emission landscapes and spectral curve resolution (parallel factor analysis). The higher oxygen concentration, the more sensory degraded were the samples. Violet light resulted in slightly higher degrees of photo‐oxidation than green and red light for low oxygen concentrations. Bleaching rate and course as function of O2 concentration differed between the photosensitizers. It is suggested that the rate of photobleaching is a balance between type I and type II photoreactions.
Simple Photodynamic Therapy Dose Models Fail to Predict the Survival of MLL Cells After HPPH–PDTIn Vitro
Authors: Weston Mark A. , Patterson Michael S. 
Published: December 2008

AbstractFluorescence photobleaching, photodynamic therapy (PDT) oxygen consumption and clonogenic cell survival were investigated during 2‐(1‐hexyloxethyl)‐2‐devinyl pyropheophoribde‐a (HPPH) PDT of MAT‐LyLu cellsin vitro. Cells were incubated with HPPH concentrations of 0.24, 1.2, 3.6 or 12 μmfor 4 h and then treated with 650 nm light under oxygenated and hypoxic conditions. Fluorescence spectra were acquired during treatment and photobleaching was quantified using singular value decomposition of the spectra. Cell survival was measured at set times during the treatment using a colony forming assay. Intracellular fluorescence lifetime measurements were also performed at each incubation concentration. The photobleaching kinetics did not follow first‐ or second‐order kinetics and the fluorescence lifetime was similar for all intracellular concentrations. As the intracellular concentration of drug was increased, the amount of singlet oxygen and the absorbed quanta per cell required to achieve the same cell kill increased. Singlet oxygen dose was calculated using one‐ and two‐compartment models of HPPH intracellular distribution. It was found that a two‐compartment model, in which a PDT‐sensitive binding site saturates at low concentrations, accounts for the observed photobleaching, oxygen consumption and cell survival.
Depth Profile of Protoporphyrin IX Fluorescence in an Amelanotic Mouse Melanoma Model
Authors: Juzenas Petras , Juzeniene Asta , Iani Vladimir , Moan Johan 
Published: December 2008

AbstractProtoporphyrin IX (PpIX) fluorescence was measured at different depths in a subcutaneous amelanotic melanoma model (LOX) in mice. PpIX was induced by topical application of 5‐aminolevulinic acid (ALA) and two of its derivatives, the methylester (MAL) and hexylester (HAL) onto the normal skin covering the tumor. The PpIX fluorescence intensity on the surface of the tumors was the highest for HAL, followed by ALA and MAL. Using equimolar concentrations (0.5 mmol g−1), HAL induced nearly twice as much fluorescence as ALA did. The depth profile of PpIX fluorescence was measured at different layers of the tumor, which was carefully sliced and controlled in situ ex vivo. The PpIX fluorescence was mainly localized within the upper 2 mm of the tissue for ALA and within 1 mm for MAL and HAL. There were no significant differences in the shape of the fluorescence excitation spectra, but the long wavelength excitation peak (633 nm) was so weak that these results are unreliable for depth estimation. When considering the low fluorescence intensity (around 5% of the intensity at the tumor surface), the actual penetration depth of HAL was comparable to that of ALA. The fluorescence after topical application of ALA and HAL was significantly above the background level down to a depth of around 6 mm, and there were traces of PpIX fluorescence even at the tumor base (10 mm). The fluorescence after topical application of MAL was detectable down to 1 mm. In the depth of 2–6 mm, the fluorescence was slightly higher for HAL than for ALA. Using the estimated diffusion coefficients for topically applied ALA (0.16 ± 0.03 mm2 h−1), MAL (0.045 ± 0.005 mm2 h−1) and HAL (0.037 ± 0.003 mm2 h−1), the behavior of the drugs after different application times could be estimated in this tumor model.
ORIGINAL ARTICLE: Coinfection rates in φ6 bacteriophage are enhanced by virus‐induced changes in host cells
Authors: Joseph Sarah B. , Hanley Kathryn A. , Chao Lin , Burch Christina L. 
Published: December 2008

AbstractTwo or more viruses infecting the same host cell can interact in ways that profoundly affect disease dynamics and control, yet the factors determining coinfection rates are incompletely understood. Previous studies have focused on the mechanisms that viruses use to suppress coinfection, but recently the phenomenon of enhanced coinfection has also been documented. In the experiments described here, we explore the hypothesis that enhanced coinfection rates in the bacteriophage φ6 are achieved by virus‐induced upregulation of the φ6 receptor, which is the bacterial pilus. First, we confirmed that coinfection enhancement in φ6 is virus‐mediated by showing that φ6 attaches significantly faster to infected cells than to uninfected cells. Second, we explored the hypothesis that coinfection enhancement in φ6 depends upon changes in the expression of an inducible receptor. Consistent with this hypothesis, the closely related phage, φ12, that uses constitutively expressed lipopolysaccharide as its receptor, attaches to infected and uninfected cells at the same rate. Our results, along with the previous finding that coinfection in φ6 is limited to two virions, suggest that viruses may closely regulate rates of coinfection through mechanisms for both coinfection enhancement and exclusion.
State of Mind, State of Order: Reactions to Ethnic Unrest in the Islamic Republic of Iran
Authors: Elling Rasmus Christian 
Published: December 2008

AbstractBy analysing the symbols and language employed in official statements on two cases of ethnic minority unrest in Iran in 2005–6, the article shows how the Islamic Republic's ideologues and leaders are responding to threats against national security and to alternative definitions of identity. In this emerging discourse, religious and secular notions of patriotism and loyalty are interwoven and an Islamist/nationalist conceptualisation of Iranian nationhood is defended. This interesting process of paradoxical dynamics is an important part of the ongoing struggle to define the identity of Iran in a region boiling with political and cultural conflicts.
Civic and Ethnic Conceptions of Nationhood in the First Czechoslovak Republic: Emanuel Rádl's Theories of Nationalism1
Authors: Novotna Tereza 
Published: December 2008

AbstractExternal forces are often seen as a source of the break‐up of Czechoslovakia before World War II. This paper, however, argues that no less significant were the tensions between Czechs and Germans. One of the Czech thinkers who saw the fragility of Czechoslovakia was Emanuel Rádl. The author examines Rádl's concepts of nation and nationality, and introduces his idea of the contractual state. The author criticises certain incongruities in Rádl's theoretical suggestions. Nevertheless, she finds prescient Rádl's vision that the solution of the relation between Czechs and Germans would affect the entire Central European region.
Debio 025, a Cyclophilin Binding Molecule, Is Highly Efficient in Clearing Hepatitis C Virus (HCV) Replicon-Containing Cells When Used Alone or in Combination with Specifically Targeted Antiviral Therapy for HCV (STAT-C) Inhibitors
Authors: Coelmont Lotte , Kaptein Suzanne , Paeshuyse Jan , Vliegen Inge , Dumont Jean-Maurice , Vuagniaux Grégoire , Neyts Johan 
Published: December 2008

ABSTRACTDebio 025 is a potent inhibitor of hepatitis C virus (HCV) replication (J. Paeshuyse et al., Hepatology 43:761-770, 2006). In phase I clinical studies, monotherapy (a Debio 025 dose of 1,200 mg twice a day) resulted in a mean maximal decrease in the viral load of 3.6 log10units (R. Flisiak et al., Hepatology 47:817-826, 2008), whereas a reduction of 4.6 log10units was obtained in phase II studies when Debio 025 was combined with interferon (R. Flisiak et al., J. Hepatol., 48:S62, 2008). We here report on the particular characteristics of the in vitro anti-HCV activities of Debio 025. The combination of Debio 025 with either ribavirin or specifically targeted antiviral therapy for HCV (STAT-C) inhibitors (NS3 protease or NS5B [nucleoside and nonnucleoside] polymerase inhibitors) resulted in additive antiviral activity in short-term antiviral assays. Debio 025 has the unique ability to clear hepatoma cells from their HCV replicon when it is used alone or in combination with interferon and STAT-C inhibitors. Debio 025, when it was used at concentrations that have been observed in human plasma (0.1 or 0.5 μM), was able to delay or prevent the development of resistance to HCV protease inhibitors as well as to nucleoside and nonnucleoside polymerase inhibitors. Debio 025 forms an attractive drug candidate for the treatment of HCV infections in combination with standard interferon-based treatment and treatments that directly target the HCV polymerase and/or protease.