bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lean method as a clinical pathway facilitator in patients with lung cancer
Authors: Aasebø Ulf , Strøm Hans Henrik , Postmyr Merete 
Published: September 2011

AbstractIntroduction:  Patient flow during workup for lung cancer is often difficult to influence because of delay at many levels: patient delay, doctors' delay and waiting time for X‐ray and CT scan, referral to specialist, and waiting time for chemotherapy and radiotherapy or surgery. A mean workup time of 4 months is not unusual.Objectives:  To improve quality and shorten the workup time for patients with lung cancer.Methods:  It was decided to employ a program designed by the Toyota car industry, the Lean process, as a tool to improve workup time. A Lean process implicates all levels of an institution with project and focus groups having workshops to analyse present status and suggest improvements.Results:  Since introducing the Lean project, we have decreased the workup time from a mean of 64 days to 16 days, and the median time from diagnosis to surgery was reduced from 26.5 days to 15 days.Conclusion:  It is feasible to improve patient flow for patients with lung cancer by employing the Lean method as a pathway instrument.Please cite this paper as: Aasebø U, Strøm HH and Postmyr M. The Lean method as a clinical pathway facilitator in patients with lung cancer. Clin Respir J 2012; 6: 169–174.
Caries and periodontal disease in patients with Parkinson's disease
Authors: Müller Thomas , Palluch Romuald , ackowski Jochen J 
Published: September 2011

ABSTRACTParkinson's disease (PD) has been associated with aging, reduced fine motor skills, and malnutrition caused by eating soft sticky foods and a decreased liquid intake, which may contribute to the onset of caries, periodontal disease, and tooth loss. The objective of this study was to investigate the oral health of 101 patients with PD (mean age: 66.2 ± 10.5 years) and compare them to 75 control subjects (CO) (mean age 71 ± 10.53). Patients with PD had poorer oral health than the control group (papilla bleeding index: PD 6.97 ± 8.34; CO 2.12 ± 2.73). Lower frequencies of daily toothbrushing (PD: 1.69 ± 0.83; CO: 2.08 ± 0.80), longer time since the last dentist visit (PD: 1.94 ± 1.49; CO: 1.21 ± 0.60 years), and reduced salivary flow (PD: 2.69 ± 0.94; CO: 3.53 ±1.11 ml). All of these factors may be related to the gingival recession and tooth mobility found in our patients with PD. Individuals with PD, their caregivers, and their physicians need to focus more on their oral health and quality of oral hygiene.
Activation of β‐adrenergic receptors increases the in vitro migration of malignant hepatocytes
Authors: Lodewyks Carly , Rodriguez Jose F. , Yan Jing , Lerner Betty , Sun DongFeng , Rempel Julia D. , Uhanova Julia , Labine Meaghan , Minuk Gerald Y. 
Published: September 2011

Aim:  Activation of adrenergic receptors (AR) has been reported to enhance the growth and invasion of various malignancies. The effects of AR agonists on malignant hepatocyte proliferation and migration have yet to be determined.Methods:  PLC/PRF/5 (PLC) and Huh‐7 cells were exposed to a wide range of concentrations of the AR agonists noradrenaline (NA) and isoprenaline. Cell proliferation, migration, intracellular cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) and C (PKC), matrix metalloproteinases (MMP)‐2, ‐3, ‐7 and ‐9, and α1‐, β1‐ and β2‐AR expression were documented in both cell lines.Results:  Cell proliferative activity was unaltered following exposure to physiological and stress‐related concentrations of AR agonists but migration was accelerated, an effect that was inhibited by the nonselective β‐AR antagonist labetalol. cAMP, PKA, PKC or MMP expression remained unchanged. Although α1‐ and β1‐AR expressions were abundant, β2‐AR expression was limited in both cell lines.Conclusion:  Unlike other malignancies studied to date, in this study, the proliferative activity of malignant hepatocytes was not increased by exposure to AR agonists, a finding that could be explained by downregulation of β2‐AR expression. The increase in malignant hepatocyte migration observed remains unexplained but does not appear to involve adenyl cyclase or MMP signaling pathways.
Favorable factors for re‐treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus
Authors: Tamori Akihiro , Kioka Kiyohide , Kurai Osamu , Sakaguchi Hiroki , Enomoto Masaru , Fujii Hideki , Kobayashi Sawako , Iwai Shuji , Morikawa Hiroyasu , Yamaguchi Seiko , Kawasaki Yasuko , Oka Hiroko , Tanaka Yasuhito , Kawada Norifumi 
Published: September 2011

Aim:  Effect of re‐treatment for pegylated interferon (PEG‐IFN) plus ribavirin was not fully evaluated. We examined the effects of re‐treatment with PEG‐IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with combination therapy.Methods:  We examined 38 patients who were re‐treated with PEG‐IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non‐responders and 24 were relapsers after previous treatment with PEG‐IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients.Results:  The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non‐responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re‐treated patients who had turned hepatitis C virus (HCV) RNA‐negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re‐treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re‐treatment, patients with complete viral suppression at week‐12 achieved a significantly higher SVR rate (P = 0.001).Conclusions:  Re‐treatment with PEG‐IFN α2a plus ribavirin therapy is effective in patients who relapse after a course of PEG‐IFN α2b plus ribavirin therapy. Re‐treatment is a particularly useful option for patients who achieve early viral clearance during previous therapy.
Subconjunctival voriconazole for the treatment of mycotic keratitis in a horse
Authors: Gilmour M. A. 
Published: September 2011

SummaryFungal keratitis in the horse is a common but challenging disease. This report describes the successful treatment ofFusariumkeratitis with both topical and subconjunctival voriconazole 1%. Voriconazole is a new triazole antifungal that has demonstrated efficacy against common fungal pathogens. Topical voriconazole is able to penetrate the intact corneal epithelium making it a good choice for superficial or deep mycotic keratitis. Reports of subconjunctival use of antifungal drugs are sparse in the veterinary literature. We found subconjunctival voriconazole was well tolerated and easy to safely administer.
Cytotoxic constituents of propolis inducing anticancer effects: a review
Authors: Watanabe Maria Angélica Ehara , Amarante Marla Karine , Conti Bruno José , Sforcin José Maurício 
Published: September 2011

Abstract

Objectives
Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.

Key findings
The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.

Summary
Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.
Correlation of Susceptibility of Cryptococcus neoformans to Amphotericin B with Clinical Outcome
Authors: Larsen R. A. , Bauer M. , Pitisuttithum P. , Sanchez A. , Tansuphaswadikul S. , Wuthiekanun V. , Peacock S. J. , Simpson A. J. H. , Fothergill A. W. , Rinaldi M. G. , Bustamante B. , Thomas A. M. , Altomstone R. , Day N. P. J. , White N. J. 
Published: September 2011

ABSTRACT

Testing of
Cryptococcus neoformans
for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. This report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (CSF) and the survival of 85 patients treated with amphotericin B (AMB). The Spearman rank correlation between the quantitative
in vitro
measure of susceptibility and the quantitative measure of the number of organisms in the patient's CSF was 0.37 (
P
< 0.01; 95% confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test replicate and 0.46 (
P
< 0.001; 95% CI, 0.21, 0.62) for the second susceptibility test replicate. The median
in vitro
estimated response (defined as the fungal burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was 5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died before day 14. These exploratory results suggest that patients whose isolates show a quantitative
in vitro
susceptibility response below 10 CFU/ml were more likely to survive beyond day 14.
Differential Association of Plasmodium falciparum Na
+
/H
+
Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum
Authors: Pelleau Stéphane , Bertaux Lionel , Briolant Sébastien , Ferdig Michael T. , Sinou Véronique , Pradines Bruno , Parzy Daniel , Jambou Ronan 
Published: September 2011

ABSTRACT

Plasmodium falciparum
isolates with decreased susceptibility to quinine are increasingly being found in malaria patients. Mechanisms involved in this resistance are not yet understood. Several studies claim that alongside mutations in the Pf
crt
and Pf
mdr1
genes, the Pf
nhe-1
Na
+
/H
+
exchanger polymorphism plays a role in decreasing susceptibility. However, conflicting results on the link between the Pf
nhe-1
gene and quinine resistance arise from field- and culture-adapted isolates. We tested the association between Pf
nhe-1
, Pf
crt
, and Pf
mdr1
polymorphisms in field- and culture-adapted isolates from various countries with their
in vitro
susceptibility to quinine. Field isolates presented a higher diversity of the Pf
nhe-1
microsatellite sequence than culture-adapted isolates. In culture-adapted isolates but not in field isolates, mutations in the Pf
crt
and Pf
mdr1
genes, as well as a higher number of DNNND repeats in the Pf
nhe-1
gene, were associated with a higher 50% inhibitory concentration (IC
50
) of quinine. Furthermore, most of the culture-adapted isolates with more than one DNNND repeat in the Pf
nhe-1
gene also harbored mutated Pf
crt
and Pf
mdr1
genes with an apparent cumulative effect on quinine susceptibility. This study supports the involvement of the Pf
nhe-1
gene in the modulation of the
in vitro
quinine response when associated with mutated Pf
crt
and Pf
mdr1
genes. Culture adaptation could be responsible for selection of specific haplotypes of these three genes. Methods used for drug testing might thus influence the association between Pf
nhe-1
polymorphism and quinine susceptibility. However, we do not exclude the possibility that in particular settings, Pf
nhe-1
polymorphism can be used as a molecular marker for surveillance of quinine resistance.
Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins
Authors: Reeder Nancy L. , Kaplan Jerry , Xu Jun , Youngquist R. Scott , Wallace Jared , Hu Ping , Juhlin Kenton D. , Schwartz James R. , Grant Raymond A. , Fieno Angela , Nemeth Suzanne , Reichling Tim , Tiesman Jay P. , Mills Tim , Steinke Mark , Wang Shuo L. , Saunders Charles W. 
Published: September 2011

ABSTRACT

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast,
Saccharomyces cerevisiae
. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus
Malassezia globosa
. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.
Interaction between Artemether-Lumefantrine and Nevirapine-Based Antiretroviral Therapy in HIV-1-Infected Patients
Authors: Kredo T. , Mauff K. , Van der Walt J. S. , Wiesner L. , Maartens G. , Cohen K. , Smith P. , Barnes K. I. 
Published: September 2011

ABSTRACT

Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients and those stable on nevirapine-based therapy. Both groups received the recommended artemether-lumefantrine dose. Patients were admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient sampling until 21 days. Concentrations of lumefantrine, artemether, dihydroartemisinin, and nevirapine were determined by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome was observed day 7 lumefantrine concentrations, as these are associated with therapeutic response in malaria. We enrolled 36 patients (32 females). Median (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and 336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naïve groups, respectively (
P
= 0.0002). The median artemether area under the plasma concentration-time curve from 0 to 8 h [AUC
(0-8 h)
] (
P
< 0.0001) and dihydroartemisinin AUC
(60-68 h)
(
P
= 0.01) were lower in the nevirapine group. Combined artemether and dihydroartemisinin exposure decreased over time only in the nevirapine group (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90];
P
< 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95% CI, 1.31 to 3.45];
P
= 0.002). Adverse events were similar between groups, with no difference in electrocardiographic Fridericia corrected QT and P-R intervals at the expected time of maximum lumefantrine concentration (
T
max
). Nevirapine-based ART decreased artemether and dihydroartemisinin AUCs but unexpectedly increased lumefantrine exposure. The mechanism of the lumefantrine interaction remains to be elucidated. Studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.
Dynamic Virulence: Real-Time Assessment of Intracellular Pathogenesis Links Cryptococcus neoformans Phenotype with Clinical Outcome
Authors: Mansour Michael K. , Vyas Jatin M. , Levitz Stuart M. 
Published: September 2011

ABSTRACT

While a myriad of studies have examined host factors that predispose persons to infection with the opportunistic fungal pathogen
Cryptococcus neoformans
, comparatively little has been done to examine how virulence factor differences among cryptococcal isolates may impact outcome. In the recent report by Alanio et al. (A. Alanio, M. Desnos-Ollivier, and F. Dromer, mBio 2:e00158-11, 2011), novel flow cytometry-based techniques were employed to demonstrate an association between the phenotype of
C. neoformans
-macrophage interactions, as measured by phagocytosis and intracellular replication, and patient outcomes, as determined by positive cultures on therapy and survival. These experiments establish that the prognosis of patients with cryptococcosis is influenced by the phenotypic properties of the infecting fungal isolate.
Responsibility of sport and exercise medicine in preventing and managing chronic disease: applying our knowledge and skill is overdue: Figure 1
Authors: Matheson Gordon O , Klügl Martin , Dvorak Jiri , Engebretsen Lars , Meeuwisse Willem H , Schwellnus Martin , Blair Steven N , van Mechelen Willem , Derman Wayne , Börjesson Mats , Bendiksen Fredrik , Weiler Richard 
Published: September 2011

BackgroundThe rapidly increasing burden of chronic disease is difficult to reconcile with the large, compelling body of literature that demonstrates the substantial preventive and therapeutic benefits of comprehensive lifestyle intervention, including physical activity, smoking cessation and healthy diet. Physical inactivity is now the fourth leading independent risk factor for death caused by non-communicable chronic disease. Although there have been efforts directed towards research, education and legislation, preventive efforts have been meager relative to the magnitude of the problem. The disparity between our scientific knowledge about chronic disease and practical implementation of preventive approaches now is one of the most urgent concerns in healthcare worldwide and threatens the collapse of our health systems unless extraordinary change takes place.FindingsThe authors believe that there are several key factors contributing to the disparity. Reductionism has become the default approach for healthcare delivery, resulting in fragmentation rather than integration of services. This, in turn, has fostered a disease-based rather than a health-based model of care and has produced medical school curricula that no longer accurately reflect the actual burden of disease. Trying to ‘fit’ prevention into a disease-based approach has been largely unsuccessful because the fundamental tenets of preventive medicine are diametrically opposed to those of disease-based healthcare.RecommendationA clinical discipline within medicine is needed to adopt disease prevention as its own reason for existence. Sport and exercise medicine is well positioned to champion the cause of prevention by promoting physical activity.ConclusionThis article puts forward a strong case for the immediate, increased involvement of clinical sport and exercise medicine in the prevention and treatment of chronic disease and offers specific recommendations for how this may begin.
Low-energy electron-induced decarbonylation of Fe(CO)5 films adsorbed on Au(111) surfaces
Authors: Hauchard Christelle , Rowntree Paul A. 
Published: September 2011

The decarbonylation of Fe(CO)5 adsorbed in monolayer and multilayer films on Au(111)/mica substrates has been induced by 0–20 eV electrons and studied by grazing incidence IR spectroscopy. Our results show that the cross sections for the initial stages of this process in as-deposited films range from 60–300 Å2 and show considerable variations with the incident electron energy. The high sensitivity to low-energy electrons is believed to be the result of secondary reactions of anion fragments in the film with the neighbouring Fe(CO)5 moieties, leading to increasingly massive heteronuclear Fen(CO)m species and progressive CO elimination. Continued exposure to the electron beam leads to the slower degradation of these newly created species into an Fe-rich deposit containing traces of CO. These traces are removed by subsequent heating to ~300 K. Fe(CO)5 films that have been subjected to temperatures exceeding 125 K have no measurable sensitivity to the electron beam in the 0–20 eV regime; this is believed to be due to the structural transformation of the as-deposited thin film structure into 3D aggregates. This structural motif presents a very limited quantity of the adsorbed Fe(CO)5 to the incident beam, and may also form a protective layer of the robust Fen(CO)m species during the initial stages of exposure to the electrons.
Self-organizing and self-reconfigurable event routing in ad hoc networks with causal dependency awareness
Authors: Pei Guanhong , Ravindran Binoy , Jensen E. Douglas 
Published: September 2011

Publish/Subscribe (P/S) is a communication paradigm of growing popularity for information dissemination in large-scale distributed systems. The weak coupling between information producers and consumers in P/S systems is attractive for loosely coupled and dynamic network infrastructures such as ad hoc networks. However, achieving end-to-end timeliness and reliability properties when P/S events are causally dependent is an open problem in ad hoc networks.
In this article, we present, evaluate benefits of, and compare with past work an architecture design that can effectively support timely and reliable delivery of events and causally related events in ad hoc environments, and especially in mobile ad hoc networks (MANETs).
With observations from both realistic application model and simulation experiments, we reveal causal dependencies among events and their significance in a typical use notional system. We also examine and propose engineering methodologies to further tailor an event-based system to facilitate its self-reorganizing capability and self-reconfiguration. Our design features a two-layer structure, including novel distributed algorithms and mechanisms for P/S tree construction and maintenance. The trace-based experimental simulation studies illustrate our design's effectiveness in both cases with and without causal dependencies.
MYB Is Essential for Mammary Tumorigenesis
Authors: Yu Miao Rebecca , Drabsch Yvette , Cross Ryan Stanley , Cheasley Dane , Carpinteri Sandra , Pereira Lloyd , Malaterre Jordane , Gonda Thomas J. , Anderson Robin L. , Ramsay Robert G. 
Published: September 2011

Abstract
MYB oncogene upregulation is associated with estrogen receptor (ER)-positive breast cancer, but disease requirements for MYB function in vivo have not been explored. In this study, we provide evidence of a critical requirement for MYB functions in models of human and murine breast cancer. In human breast cancer, we found that MYB expression was critical for tumor cell growth both in vitro and in vivo in xenograft settings. In transgenic knockout mice, tissue-specific deletion of the murine MYB gene caused a transient defect in mammary gland development that was reflected in delayed ductal branching and defective apical bud formation. In mouse mammary tumor virus (MMTV)-NEU mice where tumors are initiated by activation of HER2, MYB deletion was sufficient to abolish tumor formation. In the more aggressive MMTV-PyMT model system, MYB deletion delayed tumorigenesis significantly. Together, the findings in these transgenic knockout models implied that MYB was critical during an early window in mammary development when it was essential for tumor initiation, even though MYB loss did not exert a lasting impact upon normal mammary function. Two important MYB-target genes that promote cell survival, BCL2 and GRP78/BIP, were each elevated compared with nontransformed mammary epithelial cells, thereby promoting survival as confirmed in colony formation assays in vitro. Taken together, our findings establish a role for MYB at the hub of ER- and HER2-dependent pathways in mammary carcinogenesis. Cancer Res; 71(22); 7029–37. ©2011 AACR.