bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particle size matters: diagnostics and treatment of small airways involvement in asthma
Authors: Cohen J. , Postma D.S. , Douma W.R. , Vonk J.M. , De Boer A.H. , ten Hacken N.H.T. 
Published: July 2010

Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (ICS) ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed.After a 4-week run-in period using open-label fluticasone (100 μgb.i.d.), 37 mild-to-moderate asthmatics underwent provocations with standard-size (3.7 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μgs.i.d.) or fluticasone (100 μgb.i.d.) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation.Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV1) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV1(PC20) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC20by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not.Conversely,fluticasone improved large-particle AMP PC20significantly (1.32 DD; p = 0.03), whereas ciclesonide did not.Small-particle AMP provocation appears to be a promising tool to assess changes in small airway inflammation. Future adjustments are necessary taking into account the very small particle size used, with large exhaled fractions. In asthmatics reaching a PC20with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.
Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system
Authors: Pumirat Pornpan , Cuccui Jon , Stabler Richard A , Stevens Joanne M , Muangsombut Veerachat , Singsuksawat Ekapot , Stevens Mark P , Wren Brendan W , Korbsrisate Sunee 
Published: July 2010

Abstract

Background

Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl) concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis.

Results
Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS). Microarray data were verified by reverse transcriptase-polymerase chain reactions (RT-PCR). Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system.

Conclusions

B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei.
Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer
Authors: Cocco Emiliano , Casagrande Francesca , Bellone Stefania , Richter Christine E , Bellone Marta , Todeschini Paola , Holmberg Jennie C , Fu Han Hsuan , Montagna Michele K , Mor Gil , Schwartz Peter E , Arin-Silasi Dan , Azoudi Masoud , Rutherford Thomas J , Abu-Khalaf Maysa , Pecorelli Sergio , Santin Alessandro D 
Published: July 2010

Abstract

Background
Development of innovative, effective therapies against recurrent/chemotherapy-resistant ovarian cancer remains a high priority. Using high-throughput technologies to analyze genetic fingerprints of ovarian cancer, we have discovered extremely high expression of the genes encoding the proteins claudin-3 and claudin-4.

Methods
Because claudin-3 and -4 are the epithelial receptors for Clostridium perfringens enterotoxin (CPE), and are sufficient to mediate CPE binding, in this study we evaluated the in vitro and in vivo bioactivity of the carboxy-terminal fragment of CPE (i.e., CPE290-319 binding peptide) as a carrier for tumor imaging agents and intracellular delivery of therapeutic drugs. Claudin-3 and -4 expression was examined with rt-PCR and flow cytometry in multiple primary ovarian carcinoma cell lines. Cell binding assays were used to assess the accuracy and specificity of the CPE peptide in vitro against primary chemotherapy-resistant ovarian carcinoma cell lines. Confocal microscopy and biodistribution assays were performed to evaluate the localization and uptake of the FITC-conjugated CPE peptide in established tumor tissue.

Results
Using a FITC-conjugated CPE peptide we show specific in vitro and in vivo binding to multiple primary chemotherapy resistant ovarian cancer cell lines. Bio-distribution studies in SCID mice harboring clinically relevant animal models of chemotherapy resistant ovarian carcinoma showed higher uptake of the peptide in tumor cells than in normal organs. Imunofluorescence was detectable within discrete accumulations (i.e., tumor spheroids) or even single chemotherapy resistant ovarian cancer cells floating in the ascites of xenografted animals while a time-dependent internalization of the FITC-conjugated CPE peptide was consistently noted in chemotherapy-resistant ovarian tumor cells by confocal microscopy.

Conclusions
Based on the high levels of claudin-3 and -4 expression in chemotherapy-resistant ovarian cancer and other highly aggressive human epithelial tumors including breast, prostate and pancreatic cancers, CPE peptide holds promise as a lead peptide for the development of new diagnostic tracers or alternative anticancer agents.
Cyclin H expression is increased in GIST with very-highrisk of malignancy
Authors: Dorn Julian , Spatz Hanno , Schmieder Michael , Barth Thomas FE , Blatz Annette , Henne-Bruns Doris , Knippschild Uwe , Kramer Klaus 
Published: July 2010

AbstractBackgroundRisk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R0resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST.MethodsIn order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed.ResultsOf ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p ≤ 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification.ConclusionOur data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.
Molecular identification of adenovirus causing respiratory tract infection in pediatric patients at the University of Malaya Medical Center
Authors: Abd-Jamil Juraina , Teoh Boon-Teong , Hassan Eddy H , Roslan Nuruliza , AbuBakar Sazaly 
Published: July 2010

AbstractBackgroundThere are at least 51 adenovirus serotypes (AdV) known to cause human infections. The prevalence of the different human AdV (HAdV) serotypes varies among different regions. Presently, there are no reports of the prevalent HAdV types found in Malaysia. The present study was undertaken to identify the HAdV types associated primarily with respiratory tract infections (RTI) of young children in Malaysia.MethodsArchived HAdV isolates from pediatric patients with RTI seen at the University of Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia from 1999 to 2005 were used. Virus isolates were inoculated into cell culture and DNA was extracted when cells showed significant cytopathic effects. AdV partial hexon gene was amplified and the sequences together with other known HAdV hexon gene sequences were used to build phylogenetic trees. Identification of HAdV types found among young children in Malaysia was inferred from the phylograms.ResultsAt least 2,583 pediatric patients with RTI sought consultation and treatment at the UMMC from 1999 to 2005. Among these patients, 48 (< 2%) were positive for HAdV infections. Twenty-seven isolates were recovered and used for the present study. Nineteen of the 27 (~70%) isolates belonged to HAdV species C (HAdV-C) and six (~22%) were of HAdV species B (HAdV-B). Among the HAdV-C species, 14 (~74%) of them were identified as HAdV type 1 (HAdV-1) and HAdV type 2 (HAdV-2), and among the HAdV-B species, HAdV type 3 (HAdV-3) was the most common serotype identified. HAdV-C species also was isolated from throat and rectal swabs of children with hand, foot, and mouth disease (HFMD). Two isolates were identified as corresponding to HAdV-F species from a child with HFMD and a patient with intestinal obstruction.ConclusionsHAdV-1 and HAdV-2 were the most common HAdV isolated from pediatric patients who sought treatment for RTI at the UMMC from 1999 to 2005. HAdV-B, mainly HAdV-3, was recovered from ~22% of the patients. These findings provide a benchmark for future studies on the prevalence and epidemiology of HAdV types in Malaysia and in the region.
Regular Khat (Catha edulis) chewing is associated with elevated diastolic blood pressure among adults in Butajira, Ethiopia: A comparative study
Authors: Getahun Workineh , Gedif Teferi , Tesfaye Fikru 
Published: July 2010

AbstractBackgroundFresh leaves and buds of the Khat plant (Catha edulis) contain Cathinone, an amphetamine like alkaloid responsible for its pharmacological action. Chewing of Khat has been associated with a transient rise in blood pressure and heart rate in experimental studies. Few studies examined the effect of regular or frequent Khat chewing on blood pressure at the population level. This study was conducted to examine the association of regular Khat chewing with blood pressure among adults.MethodsWe compared systolic and diastolic blood pressure of adults 35-65 years of age who reported regular chewing of Khat during the preceding five years to those who never chewed Khat during the same period. Study participants were recruited from purposively selected urban and rural villages of Butajira District in Ethiopia. The comparative groups, chewers (334) and non-chewers (330), were identified from among the general population through a house-to-house visit using a screening questionnaire. They were frequency-matched for sex and age within a five-year range. Data were collected through structured interviews and physical measurements including blood pressure, weight and height.ResultsThe prevalence of hypertension was significantly higher among Khat chewers (13.4%) than non-chewers (10.7%), odds ratio (OR) = 1.66 (95% confidence interval (CI) 1.05, 3.13). A considerably high proportion of chewers (29.9%) than non-chewers (20.6%) had sub-optimal diastolic blood pressure (> 80 mmHg). The mean (sd) diastolic blood pressure was significantly higher among Khat chewers [75.0 (11.6)] than non-chewers [72.9 (11.7)], P < 0.05. Similarly, Khat chewers had significantly higher mean (sd) heart rate [76.3 (11.5)] than non-chewers [73.9 (12.6)], P < 0.05. There was no significant difference in mean systolic blood pressure between the two groups.ConclusionRegular chewing of Khat is associated with elevated mean diastolic blood pressure, which is consistent with the peripheral vasoconstrictor effect of Cathinone. Regular Khat chewing may have sustained effects on the cardiovascular system that can contribute to elevated blood pressure at the population level.
Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk
Authors: Njike Valentine , Faridi Zubaida , Dutta Suparna , Gonzalez-Simon Anjelica L , Katz David L 
Published: July 2010

AbstractBackgroundLimiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk.ObjectiveTo assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults.MethodsRandomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel.ResultsSingle dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%;p= 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%;p< 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL;p< 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL;p= 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline.ConclusionsEgg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.
An adaptation model for trabecular bone at different mechanical levels
Authors: Gong He , Zhu Dong , Gao Jiazi , Lv Linwei , Zhang Xizheng 
Published: July 2010

Abstract

Background
Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different.

Methods
An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method.

Results
The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone.

Conclusions
The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological environments.
A simple, sensitive high-performance liquid chromatography -ultraviolet method for the quantification of concentration and steady-state pharmacokinetics of itraconazole and hydroxyitraconazole
Authors: Miura M , Takahashi N , Nara M , Fujishima N , Kagaya H , Kameoka Y , Saitoh H , Tagawa H , Sawada K 
Published: July 2010

Background A steady-state trough plasma itraconazole concentration greater than 500 ng/mL is a therapeutic target for itraconazole. A simple, rapid and sensitive high-performance liquid chromatography-based method was developed for quantitation of itraconazole and hydroxyitraconazole in human plasma. Methods Itraconazole and hydroxyitraconazole were separated using a mobile phase of 0.5% KH2PO4 (pH 6.0)-acetonitrile (30:70, v/v) on a CAPCELLPAK C18 MGII column at a flow rate of 0.5 mL/min and ultraviolet absorbance at 260 nm. Results The analysis required 200 μL of plasma and involved a rapid, simple solid-phase extraction with an Oasis HLB cartridge, which resulted in recoveries of 87–92% for itraconazole and 91–94% for hydroxyitraconazole. The lower limit of quantification for itraconazole and hydroxyitraconazole was 5 ng/mL each. Intra- and interday coefficients of variation for itraconazole and hydroxyitraconazole were less than 11.3% and 12.2%, respectively, and accuracies were within 11.7% and 4.5% over the linear range, respectively. Although the steady-state plasma concentrations of itraconazole and hydroxyitraconazole ranged from 506 to 2482 ng/mL and from 766 to 2444 ng/mL, respectively, after a two-day loading dose of 400 mg/day intravenous itraconazole followed by the administration of 200 mg/day itraconazole oral solution, calibration curves of itraconazole and hydroxyitraconazole showed positive linearity in a concentration range of 5–2500 and 50–2500 ng/mL, respectively. Conclusions Our results indicate that this method is applicable for the monitoring of plasma levels of itraconazole and hydroxyitraconazole in a clinical setting. Furthermore, the regimen presented here might also be effective in preventing infection, but further studies with large sample sizes are necessary to investigate this avenue.
Measurement of short-chain fatty acids in human faeces using high-performance liquid chromatography: specimen stability
Authors: Torii T , Kanemitsu K , Wada T , Itoh S , Kinugawa K , Hagiwara A 
Published: July 2010

Background Short-chain fatty acids such as lactic acid produced by the intestinal bacterial flora have various physiological actions involved in health, and it is important to determine the concentrations of faecal short-chain fatty acids and evaluate their relationship with large intestinal diseases. In this study, we evaluated the highly selective and sensitive simultaneous measurement of both volatile and non-volatile short-chain fatty acid hydrazides using high-performance liquid chromatography (HPLC). Materials and methods Faeces treated with ethanol were used as analytic samples. Short-chain fatty acids were measured as fatty acid hydrazides by HPLC. Results For 12 types of short-chain fatty acid, the results regarding linearity, recovery tests and reproducibility were favourable. Faeces treated with ethanol could be stored at room temperature. Discussion The stability of short-chain fatty acids in faeces at room temperature was statistically analysed. Faeces stored without treatment with ethanol showed increases/decreases in the concentrations of short-chain fatty acids, which may be due to assimilation by intestinal bacteria. However, specimen in 70% ethanol and stored in room temperature exhibited no substantial changes in concentrations of short-chain fatty acids up to seven days.
What is the Role of Senior House Officer or Dental Foundation Year Two Posts in Professional Careers?
Authors: Gallagher Jennifer E , Bates Timothy J , Kalsi Harpoonam , Shah Aneesha , Wang Yon Jon , Newton J Timothy 
Published: July 2010

Aims To investigate the motivations for, and perceived benefits of, undertaking senior house officer (SHO) posts, and to explore the career pathways of those who do, examining trends in successive cohorts. Method Postal cross-sectional questionnaire survey of all dental and maxillofacial SHOs (DF2s) who had worked for two South London hospitals within the previous nine years (n=137). Respondents were grouped into three cohorts to enable responses to be examined in relation to respondents’ entry to their first SHO post. Results There were responses from 83 (61%) potential participants. The most frequent motivation for carrying out SHO posts from 79 (95%) of the respondents was the desire to ‘learn from experienced clinicians’. The most common perceived benefit reported by those who had completed posts at the time of the survey was ‘an improved understanding of the role of the hospital dental service’ from 68 (97%) of those who answered this question. Difficulty in securing a job in general dental practice was not reported as a notable motivating factor, either before or after the implementation of the new dental contract. ‘Fulfil approved training post requirements for postgraduate examinations’ reduced as a motivator from 28 (88%) for the earlier cohort of SHOs to nine (36%) for the more recent cohort. Fifty-four of 78 (69%) respondents declared a definite plan to seek admission to the General Dental Council Specialist Lists in future, 24 (83%) in the first cohort, compared with 11 (46%) in the last ( P=0.05). Of the males, 13 (52%) were significantly more likely to report that they were currently working in general practice compared with 15 (27%) females ( P=0.028). Conclusion The findings suggest that multiple benefits are identified from undertaking SHO posts. However, some of the motivations for undertaking SHO posts may have changed over the nine-year period investigated. Possible influences are discussed. This paper highlights the perceived benefits of junior training posts at a time of significant transition within the profession.