bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and response predictive factors of erlotinib in a non-small cell lung cancer unselected European population previously treated: A retrospective, observational, multicentric study
Authors: Cioffi Pasquale , Marotta Valerio , Fanizza Caterina , Giglioni Adriano , Natoli Clara , Petrelli Fabio , Grappasonni Iolanda
Published: December 2012

Aims and background:

Erlotinib approval was supported by the positive results of a large multicentric phase III trial (BR.21 study) that included 10% Asiatic patients and the remaining were North-American Caucasian. It is well-known that the efficacy of tyrosine kinase inhibitors is strongly influenced by ethnicity and other genetic factors. It is, therefore, relevant to establish whether the same profile of efficacy is seen in an unselected population and whether the results of BR.21 can be generalized to other patient populations, such as that described here.

Methods:

In this retrospective, observational, multicentric study, we assessed effectiveness and potentially response predictive factors in 222 unselected Italian patients, with stage IIIB/IV non-small-cell lung cancer, with performance status from 0 to 3, who had received at least one line of chemotherapy, treated with the standard dose of erlotinib (150 mg once daily) until disease progression or unacceptable toxicity.

Results:

The disease control rate was 60.9% (135 patients). Median progression-free survival and overall survival times were 3.1 months and 7.97 months, respectively. The characteristics of non-smoker, female gender, performance status 0 or 1 were associated with a significantly better prognosis in terms of disease control rate and were also predictive of longer overall survival and progression-free survival. The 1-year survival rate was 38.79%. Even though Italian patients baseline characteristics were strongly different to those reported in pivotal BR.21 trial in terms of age, performance status, line treatment and ethnic group, our study confirms the favorable effectiveness profile in real clinical practice of erlotinib according to results from the pivotal study BR.21.

Conclusions:

Today, we know that epidermal growth factor receptor (EGFR) status assessment is mandatory before starting first-line therapy and that the presence of only certain clinical characteristics initially associated with sensitivity to EGFR-tyrosine kinase inhibitors, as reported in this study, is not sufficient in selecting patients candidates to such treatments.
Adverse drug events resulting in admission to the intensive care unit in oncology patients: Incidence, characteristics and associated cost
Authors: Nazer Lama H , Eljaber Rana , Rimawi Dalia , Hawari Feras I
Published: December 2012

Purpose:

Describe the incidence, characteristics and cost of adverse drug events that necessitate admission to the intensive care unit in oncology patients.

Methods:

This was a prospective observational 5-months study at a medical/surgical intensive care unit of a comprehensive teaching cancer center. Patients admitted to the intensive care unit were screened to determine whether the admission was due to an adverse drug event. The adverse drug events were characterized based on the suspected medication, system involved and preventability. Patient demographics, length of stay, mortality and the total patient charges during their intensive care unit stay were recorded.

Results:

During the study period, 249 patients were screened and an adverse drug event was the primary cause of 57 (22.9%) admissions. The most common medications associated with an adverse drug event requiring intensive care unit admission were antineoplastics ( n = 37), analgesics ( n = 9) and anticoagulants ( n = 4). Ten adverse drug events were considered preventable. The average length of stay for patients with adverse drug events resulting in intensive care unit admission was 6.2 days ±9.8 (SD) and the mortality rate was 28.1%. Hematological malignancy was independently associated with adverse drug events resulting in intensive care unit admission. The average patient charges for the intensive care unit stay was US$11,692 ± 17,529 (SD), which corresponded to about US$1.5 million in annual patient charges for a 12-bed intensive care unit at a cancer institution.

Conclusions:

Adverse drug events resulting in intensive care unit admission in oncology patients are common and often associated with significant morbidity, mortality, and cost.
Parallelization of shallow water simulations on current multi-threaded systems
Authors: Lobeiras Jacobo , Viñas Moisés , Amor Margarita , Fraguela Basilio B , Arenaz Manuel , García JA , Castro MJ
Published: December 2012

In this work, several parallel implementations of a numerical model of pollutant transport on a shallow water system are presented. These parallel implementations are developed in two phases. First, the sequential code is rewritten to exploit the stream programming model. And second, the streamed code is targeted for current multi-threaded systems, in particular, multi-core CPUs and modern GPUs. The performance is evaluated on a multi-core CPU using OpenMP, and on a GPU using the streaming-oriented programming language Brook+, as well as the standard language for heterogeneous systems, OpenCL.
Applying a coping with stress questionnaire for cancer patients to patients with non-cancer chronic illnesses
Authors: Orive Miren , Quintana Jose M , Vrotsou Kalliopi , Las Hayas Carlota , Bilbao Amaia , Barrio Irantzu , Matellanes Begoña , Padierna Jesús A
Published: December 2012

One of the few instruments to evaluate coping skills among patients with chronic illnesses is the Cuestionario de Afrontamiento al Estrés para Pacientes Oncológicos (CAEPO), created initially for cancer patients. We evaluate how well CAEPO applies to patients with non-cancer chronic illnesses. A total of 344 patients (115 with chronic hepatitis C, 120 with inflammatory bowel disease and 109 with recurrent vertigo) completed the CAEPO. Exploratory factor analysis and Cronbach’s alpha provide only partial support for the seven factors suggested by the original CAEPO. A streamlined version with fewer dimensions and items may be a better solution for identifying coping strategies among these patients.
Adolescents’ negative attitudes towards non-drinkers: A novel predictor of risky drinking
Authors: Regan Daniel , Morrison Todd G
Published: December 2012

The Regan Attitudes towards Non-Drinkers Scale was developed to address the concept that consumption of alcohol may serve as a means of avoiding social costs associated with being a non-drinker. This study sought to examine the Regan Attitudes towards Non-Drinkers Scale within a sample of Irish school-age adolescents. Results indicated that the Regan Attitudes towards Non-Drinkers Scale was a statistically significant predictor of self-reported problematic drinking. The findings of this study underscore the importance of this newly identified construct and highlight the necessity of further empirical tests of the Regan Attitudes towards Non-Drinkers Scale.
Group status, perceptions of agency, and the correspondence bias: Attributional processes in the formation of stereotypes about high and low status groups
Authors: Nier Jason A. , Bajaj Priya , McLean Meghan C. , Schwartz Elizabeth
Published: December 2012

The Stereotype Content Model proposes that competence (or alternatively, agency) is a fundamental dimension of stereotypes. According to this model, beliefs about agency are partially due to the status relations between groups, such that high status groups are perceived to possess agency, whereas low status groups are perceived to lack agentic characteristics. Despite the considerable support for this model, the psychological processes that produce these stereotypes have not been fully explored. In the current studies, we examined whether the correspondence bias may be partially responsible for the stereotype that members of low status groups lack agentic characteristics, relative to those who belong to high status groups. Across both studies, a measure of the correspondence bias predicted such stereotypical beliefs, even after accounting for variables that are known to be associated with beliefs about high and low status groups. This effect was observed when beliefs about the status of groups were experimentally manipulated, and when we measured stereotypical beliefs about two sets of actual high and low status groups.
The Service Pattern-Oriented Smart Bedroom Based on Elderly Spatial Behaviour Patterns
Authors: Lee Hyunsoo , Park Sung Jun , Kim Mi Jeong , Jung Ji Yea , Lim Hae Won , Kim Jeong Tai
Published: December 2012

This paper stresses the importance of the service patterns matching the behaviours of residents in improving comfort, safety, convenience, etc in homes for the aged. The paper particularly focuses on the smart services (SVs) a bedroom can provide for the elderly. This paper derives three service patterns (SVPs) based on the elderly spatial behaviour patterns (SBP). The first pattern is SVP1 (intrusion/theft prevention → temperature/humidity control → health care/emergency system) for solving potential problems during sleep in mobility and cognition of the elderly. The second pattern is SVP2 (temperature/humidity control → health care, medical examination → smart furniture) for controlling interior environmental conditions such as temperature, humidity, ventilation, lighting, etc. The final pattern is SVP3 (entertainment → remote control, smart furniture → intrusion/theft prevention → temperature/humidity control, lighting control → health care, emergency call) that offers entertainment and leisure for the elderly to relieve their loneliness. Suggested service patterns largely place a great deal of weight on such aspects as comfort, health and emergency, because smart technologies are included for the convenience of old people who are fragile from physical, psychological and social perspectives. All service patterns provide a healthy management of the elderly. Moreover, each service pattern can be customized to behaviour patterns determined by habit, lifestyle and needs.
Energy-Saving Potential of LED Lighting Systems
Authors: Yun Geun Young , Jung Hoyoun , Kim Jeong Tai
Published: December 2012

Light emitting diode (LED) with its long lifetime of up 100,000 h has been receiving keen interest as there has been a rapid increase in luminous efficacy of LED recently. One interesting feature of LED is that its spectral power distributions can be easily controllable by regulating electric circuits to LED. Therefore, the same colour from LED can have quite different spectral power distribution due to metamerism. This is important as spectral power distribution is a key factor that can affect human circadian rhythm and subjective responses to changes with different spectral power distribution under the same illuminance level. The study aims to explore the energy saving potentials of LED lighting system by modulating spectral power distributions. The wavelength controllable LED system was developed in the previous study and was used in this study. Dynamic building simulations were carried out in order to quantify the total energy use including energy demands for lighting, cooling and heating indoors. Our study indicates that subjects would tend to feel brighter under red-colour emphasizing spectral power distribution, as compared to their perception under blue-colour. Also, simulation results indicate that total energy consumption can be reduced by 38% by changing spectral power distribution without sacrificing subjects’ visual comfort.
Thermal Extractor Analysis of VOCs Emitted from Building Materials and Evaluation of the Reduction Performance of Exfoliated Graphite Nanoplatelets
Authors: Lee Jeong-Hun , Kim Junhyun , Kim Sumin , Kim Jeong Tai
Published: December 2012

This study evaluated the amount of volatile organic compounds (VOCs) emitted from building materials, such as wallpaper, paint, adhesive and wood-flooring material, using a thermal extractor (TE). To evaluate the performance of TE on VOCs emissions of building materials according to temperature variation, all specimens were measured at two temperatures: 25°C and 35°C. Through emission results, the acceleration effect on the diffusion of VOCs in the material at the elevated temperature and the feasibility of TE on VOCs emission test according to temperature variation were confirmed. In addition, exfoliated graphite nanoplatelets (xGnP) made by using shape modification process to improve porosity of graphite, which can remove VOCs by sorption was applied to materials. The adsorption amounts of VOCs by exfoliated xGnP were evaluated at 35°C with each specimen. The xGnP as a porous material had an effect on the material emissions; the emission amounts were reduced. The emission tests were conducted with the same exposed surface area for each specimen. As the temperature increased, VOCs emission rates increased from approximately 2 to 5 times. And the adsorption performance of xGnP showed that the reduction percentage of VOCs was 9% to 81%.
Collision consequence estimation model for chemical tankers
Authors: Sormunen Otto-Ville E , Ehlers Sören , Kujala Pentti
Published: December 2012

Chemical tanker traffic constitutes a hazard for the environment; large chemical spills caused by, for example, ship–tanker collisions can have catastrophic effects in similar manner to oil spills. For this reason, it is important to have a generalized spill model for chemical tankers, so that the spill size for a given geographical area can be assessed. The spill volume can be used as an indicator of risk in the given area. Furthermore, such a model can be used to analyze the possible effects of potential risk-mitigating measures such as requiring wider double hulls for chemical tankers. In this article, a spill model is proposed, which for a given collision scenario can model the penetration, spill probability, and size caused by a ship striking a chemical tanker. This is done using finite element method, MATLAB, and statistical metamodels with ship particulars extracted mainly from automatic identification system data from the Gulf of Finland.
Investigation of free surface flow generated by a planing flat plate using smoothed particle hydrodynamics method and FLOW3D simulations
Authors: Ghadimi Parviz , Dashtimanesh Abbas , Farsi Mohammad , Najafi Saeed
Published: December 2012

In this article, smoothed particle hydrodynamics method is applied in order to study the free surface flow generated by two-dimensional planing flat plate. For this purpose, a two-dimensional smoothed particle hydrodynamics code is developed and validated by the well-known dam breaking problem. Four trim angles and three different velocities are considered to perform a parametric study to examine their physical effects. The obtained results from smoothed particle hydrodynamics are compared against the corresponding Reynolds-averaged Navier Stokes solutions. It is observed that at lower velocities, there exists a good agreement between the smoothed particle hydrodynamics and Reynolds-averaged Navier Stokes solutions, while at higher velocities, some inconsistency is observed. A brief discussion is presented to clarify the physical reasons behind the increase of the velocity and the height of the spray with the trim angle. Some formulas have also been derived to examine the variation of the ratio between the final wetted length of the flat plate and the initial wetted length at different velocities and trim angles.
Speakers and the Spotlight
Authors: Johnson Tyler , O’Grady Caitlin
Published: December 2012

Previous scholarship has described how members of Congress struggle to attract media attention. The Speaker of the House, however, is uniquely positioned to drive media agendas. That position may be conditioned though by the framework in which the Speaker operates, shocks to the system of leadership in the House, and the process of legislating. We inquire into the conditions under which the Speaker of the House receives increased or decreased attention from newspapers, network newscasts, and cable newscasts. We also examine the contraction and expansion of the gap between levels of presidential and Speaker coverage. We find that Speaker coverage is often shaped by increases in House polarization, changes in which party holds the position, Speaker scandal, and turning bills into laws.
Taking a New Perspective to Latino Racial Attitudes
Authors: Wilkinson Betina Cutaia , Earle Emily
Published: December 2012

Recent research has taken note of the steadfast growth of the Latino population in the United States by examining Latino attitudes toward those commonly identified as nonimmigrants, Whites and Blacks. Extant literature on Latino racial attitudes explores the determinants of Latinos’ perceptions of commonality with Whites and Blacks, yet it has greatly overlooked the impact that skin tone, a key differentiating factor of Latinos, has in explaining these attitudes. Using the 2006 Latino National Survey, we develop models that examine the extent that skin tone explains Latinos’ commonality with Whites and Blacks. We find that self-reported skin tone considerably explains Latinos’ attitudes toward Whites and Blacks with light-skinned Latinos sensing greater commonality with Whites and less commonality with Blacks than dark-skinned Latinos. We also find that skin tone moderates the relationship between linked fate with Latinos and closeness with Whites and the relationship between social contact and closeness with Blacks and Whites.
Thoracic Endovascular Repair for Aorto-Esophageal Fistula in Patients With Esophageal Carcinoma
Authors: Ishikawa Noboru , Maruta Kazuto , Oi Masaya , Iizuka Hirofumi , Kawaura Hiroyuki , Omoto Tadashi
Published: December 2012

Aorto-esophageal fistula (AEF) is a rare complication of esophageal carcinoma. Left untreated, it may be lethal due to massive upper gastrointestinal bleeding, while open thoracic surgery is associated with high operative mortality and morbidity. In contrast, thoracic endovascular aortic repair (TEVAR) for AEF is less invasive than open thoracic surgery. Here, we report 3 successful cases of AEF with esophageal carcinoma treated using TEVAR under local anesthesia in the emergent or urgent phase. General condition of all the patients was dramatically improved, but 1 patient with exsanguinations developed infection of the implanted stent-graft and died due to sepsis. The other 2 patients were treated before esophageal bleeding and remained alive for 1 year without infection. The TEVAR should be considered as early as possible in patients with advanced esophageal carcinoma receiving radiation or chemotherapy who develop early signs of AEF such as symptoms of chest discomfort or descending aortic irregularity on computed tomography scan.
The Impact of Blood Component Transfusion Practices on Patient Survival After Abdominal Aortic Aneurysm Surgery
Authors: Henriksson Anders E.
Published: December 2012

Background:

The aim of the present study was to investigate the blood transfusion practice in patients operated for abdominal aortic aneurysm (AAA) with special emphasis on massive transfusion in cases with rupture.

Material and methods:

From a database, 504 patients operated for AAA were stratified into 2 groups; an early transfusion period (1992-1999) and a late transfusion period (2000-2008) to evaluate the changes in transfusion practices over the course of time.

Results:

Patients operated for nonruptured AAA (n = 330) showed a decreased mortality rate from 4% (early transfusion period) to 1% (late transfusion period) without significant changes in the transfusion practices. In patients operated for ruptured AAA (n = 174) an unexpected low mortality rate was found compared to the 30-day mortality reported in earlier studies. The transfusion practices in ruptured AAA surgery showed a significant increase in platelet use and change of fresh frozen plasma: red blood cell ratio from 0.8 to 0.9 between the early and the late transfusion period.

Conclusion:

The present database study shows that the operating mortality for AAA surgery has declined during the past decades. The cause of the decline in mortality in patients with ruptured AAA was interpreted as partly due to a modern blood component therapy.
First Bite Syndrome Following Ipsilateral Carotid Endarterectomy
Authors: Wang Tom Kai Ming , Bhamidipaty Venu , MacCormick Murray
Published: December 2012

First bite syndrome (FBS) is characterized by unilateral pain in the parotid region after the first bite of each meal, usually following ipsilateral neck surgery. The proposed mechanism is sympathetic denervation of the parotid gland, from iatrogenic injury to the sympathetic trunk supplying this gland. Local botulinum toxin injection has emerged as a promising treatment option with favorable results. To date, there are 3 published cases in the literature describing FBS after carotid endarterectomy. We present a case of a 75-year-old gentleman who developed FBS after carotid endarterectomy, to raise the awareness of this unusual and uncommon complication.
Trends in Clinical Presentation, Management, and Mortality of Blunt Aortic Traumatic Injury Over an 18-Year Period
Authors: Malgor Rafael D. , Bilfinger Thomas V. , McCormack Jane , Shapiro Marc J. , Tassiopoulos Apostolos K.
Published: December 2012

Background:

The purpose of our study was to assess whether the trends in management of blunt thoracic aortic injury (BTAI) have changed its outcomes over the years.

Methods:

We reviewed data of 88 (0.3%) adult patients with BTAI from January 1993 to December 2010. Primary end points were trends in presentation and time to repair and early morbidity and mortality.

Results:

Of all, 63 (72%) patients with BTAI were male (age, 38 ± 17). The yearly distribution of cases and severity of associated injuries remain stable. Of all, 16 (21%) patients had no intervention, 47 (63%) underwent open repair, and 12 (16%) underwent endovascular treatment. The postoperative mortality has decreased from 29% to 9% and the time from presentation to repair has increased from 6 to 14 hours during the study period.

Conclusions:

The incidence of BTAI remains stable with a reduction in postoperative mortality rate and an increasing number of delayed interventions over the past 18 years.
Effect of hyperbaric oxygen therapy on healing in an experimental model of degloving injury in tails of nicotine-treated rats
Authors: Demirtas A. , Azboy I. , Bulut M. , Ucar B. Y. , Alabalik U. , Ilgezdi S.
Published: December 2012

The aim of this study was to investigate the effect of hyperbaric oxygen (HBO) therapy on healing in an experimental model of a degloving injury of the tails of nicotine-treated rats. Thirty-two male Sprague–Dawley rats were randomized to four groups (n = 8): nicotine (group 1); HBO (group 2); nicotine + HBO (group 3); and control (group 4). The mean length of the necrotic parts of the tails at the degloving injury site was significantly higher in group 1 compared with groups 2, 3, and 4, and was significantly lower in group 2 compared with groups 1, 3, and 4. The mean histopathological stage of ulcers at the degloving injury site was statistically significantly higher (more severe) in group 1 compared with groups 2, 3, and 4, and was statistically significantly lower in group 2 compared with groups 1, 3, and 4. It appears that the negative effects of nicotine on wound healing in degloving injuries are negated by the positive effects of immediate HBO therapy.
Immunologic mechanisms in the adaptation of swine farm workers to their work environment
Authors: Bønløkke Jakob H , Cormier Yvon , Veillette Marc , Radu Arnold , Mériaux Anne , Duchaine Caroline
Published: December 2012

Swine building exposure causes inflammatory reactions that appear to be attenuated with prolonged periods of contact. The mechanisms behind this adaptation to a dusty and endotoxin-rich environment are poorly understood. Our aim was to compare levels of selected inflammatory mediators in swine farm workers at times with differences in exposure. Participants had blood sampling done before and after each of three work shifts—two in winter and one in summer. Before one of the winter visits they had avoided pulmonary exposure to the swine buildings by wearing respiratory protection for 4 d. The other visits were done after non-protected periods of work. Protein and mRNA concentrations were measured in blood. Mixed models were used for the statistics. During summer higher concentrations of mRNA to IL-8, lymphocyte function-associated antigen 1 and bactericidal/permeability-increasing protein (BPI) were observed. BPI mRNA increased only over the work shift after the unprotected winter period ( P = 0.039). BPI decreased from elevated levels across the shift after use of respiratory protection ( P = 0.003), but was unchanged during the other two visits. The findings suggest possible roles for these proteins in adaptation to the swine building environment after repeated exposures.
Determinants of Satisfaction with Holidays and Hospitality in Rural Tourism in Spain
Authors: Frías-Jamilena Dolores M. , Del Barrio-García Salvador , López-Moreno Lorenza
Published: December 2012

An analysis of travelers’ satisfaction with a holiday trip to Spain’s Andalusia region found a distinct difference in the information sources used by first-time visitors and repeat visitors. In addition to determining the travelers’ satisfaction with the trip itself, this study also assessed the travelers’ satisfaction with the travel-related information they received before taking their trip. The framework for the study was a rural tourist trip, a little studied area. Repeat visitors relied primarily on their own experience in terms of expectations for their trips, and any external information sources they consulted had no effect on their satisfaction with the trip. Of the several external sources consulted by the first-time visitors, only mass-media advertising was associated with favorable satisfaction results for the first-timers. Other sources, including word of mouth, the internet, and noncommercial media placements (such as news stories), were associated with negative effects on satisfaction, perhaps because these sources created unrealistic expectations. Destination promotions attracted both new and returning visitors, but again the two groups had different views on which types of promotion were most effective. First-time travelers responded primarily to price discounts in some form, whereas repeat travelers were more inclined toward such nonprice promotions as gifts and prize drawings. For hospitality and tourism officials, the findings focus on the need to ensure that information sources are accurate and create appropriate expectations for first-time travelers. This may require more activity in social media, since internet sources apparently created incorrect expectations or simply offered the first-time travelers so much information that they felt overloaded.
The major CD8 T cell effector memory subset in the normal and Chlamydia trachomatis-infected human endocervix is low in perforin
Authors: Ibana Joyce A , Myers Leann , Porretta Constance , Lewis Maria , Taylor Stephanie N , Martin David H , Quayle Alison J
Published: December 2012

Background

The local tissue microenvironment plays an important role in the induction, homing, maintenance and development of effector functions of T cells. Thus, site-specific differences in phenotypes of mucosal and systemic T cell populations have been observed.Chlamydia trachomatismost commonly infects the endocervix in women, yet little is known aboutChlamydia-specific effector T cell immunity at this unique mucosal site. Our previous flow-cytometry-based study of cervical-cytobrush retrieved cells indicated that CD8 T cells are significantly increased in theC. trachomatis-infected human endocervix. The cytolytic function of CD8 T cells is important in the protective immunity against many intracellular pathogens, and requires the cytolytic granule perforin to facilitate the entry of other molecules that mediate the lysis of target cells. Determination of perforin expression of the CD8 T cell population in the endocervix would therefore provide insights on the granule-mediated cytolytic potential of these cells at this site.

Results

Our histological data revealed thatC. trachomatis-infected tissues have significantly higher numbers of CD3 and CD8 T cells compared to non-infected tissues (p<0.01), and that the majority of CD8+cells do not express perforinin situ. A subsequent flow cytometric analysis of paired blood and endocervix-derived cells (n=16) revealed that while all the CD8 T cell subsets: naïve, effector memory (TEM), central memory (TCM) and terminally differentiated effector memory (TEMRA) can be found in the blood, the endocervix is populated mainly by the TEMCD8 T cell subset. Our data also showed that perforin expression in the TEMpopulation is significantly lower in the endocervix than in the blood ofC. trachomatispositive women (n=15; p<0.0001), as well as inC. trachomatis-negative individuals (n=6; p<0.05). Interestingly, ourin vitroco-culture study suggests that the exposure of HeLa 229 cervical epithelial cells to IFN gamma could potentially induce a decrease in perforin content in CD8 TEMcells in the same microenvironment.

Conclusions

The low perforin content of CD8 TEMcells in the endocervix, the local site ofC. trachomatisinfection in women, may reflect the unique immunological environment that balances immune protection against sexually transmitted infections and immune- tolerance to support conception.
The non-specific lipid transfer protein N5 of Medicago truncatulais implicated in epidermal stages of rhizobium-host interaction
Authors: Pii Youry , Molesini Barbara , Masiero Simona , Pandolfini Tiziana
Published: December 2012

Background

The symbiotic interaction between leguminous plants and rhizobia involves two processes: bacterial infection, resulting in the penetration of bacteria in epidermal and cortical cells, and root nodule organogenesis. Root nodule symbiosis is activated by rhizobial signalling molecules, called Nodulation factors (NFs). NF perception induces the expression of several genes called early nodulins. The early nodulin N5 of Medicago truncatula is a lipid transfer protein that has been shown to positively regulate nodulation although it displays in vitro inhibitory activity against Sinorhizobium meliloti. The purpose of this work was to investigate the role of MtN5 by studying its spatial and temporal pattern of expression during the symbiotic interaction, also in relation to known components of the symbiotic signalling pathway, and by analysing the phenotypic alterations displayed by rhizobia-inoculated MtN5-silenced roots.

Results

We show here that MtN5 is a NF-responsive gene expressed at a very early phase of symbiosis in epidermal cells and root hairs. MtN5 expression is induced in vitro by rhizobial effector molecules and by auxin and cytokinin, phytohormones involved in nodule organogenesis. Furthermore, lipid signaling is implicated in the response of MtN5 to rhizobia, since the activity of phospholipase D is required for MtN5 induction in S. meliloti-inoculated roots. MtN5-silenced roots inoculated with rhizobia display an increased root hair curling and a reduced number of invaded primordia compared to that in wild type roots, but with no impairment to nodule primordia formation. This phenotype is associated with the stimulation of ENOD11 expression, an early marker of infection, and with the down-regulation of Flotillin 4 (FLOT4), a protein involved in rhizobial entry.

Conclusions

These data indicate that MtN5 acts downstream of NF perception and upstream of FLOT4 in regulating pre-infection events. The positive effect of MtN5 on nodule primordia invasion is linked to the restriction of bacterial spread at the epidermal level. Furthermore, MtN5 seems to be dispensable for nodule primordia formation. These findings provide new information about the complex mechanism that controls the competence of root epidermal cells for rhizobial invasion.
Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation
Authors: Prieto Centurion Valentin , Huang Frank , Naureckas Edward T , Camargo Jr Carlos A , Charbeneau Jeffrey , Joo Min J , Press Valerie G , Krishnan Jerry A
Published: December 2012

Background

Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation.

Methods

Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations.

Results

There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007).

Conclusions

Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients.
Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada
Authors: Santibanez Pablo , Gooch Katherine , Vo Pamela , Lorimer Michelle , Sandino Yurik
Published: December 2012

Background

Pediatric LRTI hospitalizations are a significant burden on patients, families, and healthcare systems. This study determined the burden of pediatric LRTIs on hospital settings in British Columbia and the benefits of prevention strategies as they relate to healthcare resource demand.

Methods

LRTI inpatient episodes for patients <19 years of age during 2008–2010 were extracted from the BC Discharge Abstract Database. The annual number of acute care beds required to treat pediatric LRTIs was estimated. Sub-analyses determined the burden due to infants <1 year of age and high-risk infants. Population projections were used to forecast LRTI hospitalizations and the effectiveness of public health initiatives to reduce the incidence of LRTIs to 2020 and 2030.

Results

During 2008–2010, LRTI as the primary diagnosis accounted for 32.0 and 75.9% hospitalizations for diseases of the respiratory system in children <19 years of age and infants <1 year of age, respectively. Infants <1 year of age accounted for 47 and 77% hospitalizations due to pediatric LRTIs and pediatric LRTI hospitalizations specifically due to respiratory syncytial virus (RSV), respectively. The average length of stay was 3.1 days for otherwise healthy infants <1 year of age and 9.1 days for high-risk infants (P <0.0001). 73.1% pediatric LRTI hospitalizations occurred between November and April. Over the study timeframe, 19.6 acute care beds were required on average to care for pediatric LRTIs which increased to 64.0 beds at the peak of LRTI hospitalizations. Increases in LRTI bed-days of 5.5 and 16.2% among <19 year olds by 2020 and 2030, respectively, were predicted. Implementation of appropriate prevention strategies could cause 307 and 338 less LRTI hospitalizations in <19 year olds in 2020 and 2030, respectively.

Conclusion

Pediatric LRTI hospitalizations require significant use of acute care infrastructure particularly between November and April. Population projections show the burden may increase in the next 20 years, but implementation of effective public health prevention strategies may contribute to reducing the acute care demand and to supporting efforts for overall pediatric healthcare sustainability.
De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae
Authors: Koopman Frank , Beekwilder Jules , Crimi Barbara , van Houwelingen Adele , Hall Robert D , Bosch Dirk , van Maris Antonius JA , Pronk Jack T , Daran Jean-Marc
Published: December 2012

Background

Flavonoids comprise a large family of secondary plant metabolic intermediates that exhibit a wide variety of antioxidant and human health-related properties. Plant production of flavonoids is limited by the low productivity and the complexity of the recovered flavonoids. Thus to overcome these limitations, metabolic engineering of specific pathway in microbial systems have been envisaged to produce high quantity of a single molecules.

Result

Saccharomyces cerevisiae was engineered to produce the key intermediate flavonoid, naringenin, solely from glucose. For this, specific naringenin biosynthesis genes from Arabidopsis thaliana were selected by comparative expression profiling and introduced in S. cerevisiae. The sole expression of these A. thaliana genes yielded low extracellular naringenin concentrations (<5.5 μM). To optimize naringenin titers, a yeast chassis strain was developed. Synthesis of aromatic amino acids was deregulated by alleviating feedback inhibition of 3-deoxy-d-arabinose-heptulosonate-7-phosphate synthase (Aro3, Aro4) and byproduct formation was reduced by eliminating phenylpyruvate decarboxylase (Aro10, Pdc5, Pdc6). Together with an increased copy number of the chalcone synthase gene and expression of a heterologous tyrosine ammonia lyase, these modifications resulted in a 40-fold increase of extracellular naringenin titers (to approximately 200 μM) in glucose-grown shake-flask cultures. In aerated, pH controlled batch reactors, extracellular naringenin concentrations of over 400 μM were reached.

Conclusion

The results reported in this study demonstrate that S. cerevisiae is capable of de novo production of naringenin by coexpressing the naringenin production genes from A. thaliana and optimization of the flux towards the naringenin pathway. The engineered yeast naringenin production host provides a metabolic chassis for production of a wide range of flavonoids and exploration of their biological functions.
Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea
Authors: Huang Lin-Chien , Barclay Meagan , Lee Kevin , Peter Saša , Housley Gary D , Thorne Peter R , Montgomery Johanna M
Published: December 2012

Background

During development, excess synapses form between the central and peripheral nervous systems that are then eliminated to achieve correct connectivity. In the peripheral auditory system, the developing type I spiral ganglion afferent fibres undergo a dramatic re-organisation, initially forming connections with both sensory inner hair cells (IHCs) and outer hair cells (OHCs). The OHC connections are then selectively eliminated, leaving sparse innervation by type II afferent fibres, whilst the type I afferent synapses with IHCs are consolidated.

Results

We examined the molecular makeup of the synaptic contacts formed onto the IHCs and OHCs during this period of afferent fibre remodelling. We observed that presynaptic ribbons initially form at all the afferent neurite contacts, i.e. not only at the expected developing IHC-type I fibre synapses but also at OHCs where type I fibres temporarily contact. Moreover, the transient contacts forming onto OHCs possess a broad set of pre- and postsynaptic proteins, suggesting that functional synaptic connections are formed prior to the removal of type I fibre innervation. AMPA-type glutamate receptor subunits were transiently observed at the base of the OHCs, with their downregulation occurring in parallel with the withdrawal of type I fibres, dispersal of presynaptic ribbons, and downregulation of the anchoring proteins Bassoon and Shank. Conversely, at developing type I afferent IHC synapses, the presence of pre- and postsynaptic scaffold proteins was maintained, with differential plasticity in AMPA receptor subunits observed and AMPA receptor subunit composition changing around hearing onset.

Conclusions

Overall our data show a differential balance in the patterns of synaptic proteins at developing afferent IHC versus OHC synapses that likely reflect their stable versus transient fates.
The transcription factor Uncx4.1 acts in a short window of midbrain dopaminergic neuron differentiation
Authors: Rabe Tamara I , Griesel Gundula , Blanke Stephen , Kispert Andreas , Leitges Michael , van der Zwaag Bert , Burbach J Peter H , Varoqueaux Frédérique , Mansouri Ahmed
Published: December 2012

Background

The homeobox containing transcription factor Uncx4.1 is, amongst others, expressed in the mouse midbrain. The early expression of this transcription factor in the mouse, as well as in the chick midbrain, points to a conserved function of Uncx4.1, but so far a functional analysis in this brain territory is missing. The goal of the current study was to analyze in which midbrain neuronal subgroups Uncx4.1 is expressed and to examine whether this factor plays a role in the early development of these neuronal subgroups.

Results

We have shown that Uncx4.1 is expressed in GABAergic, glutamatergic and dopaminergic neurons in the mouse midbrain. In midbrain dopaminergic (mDA) neurons Uncx4.1 expression is particularly high around E11.5 and strongly diminished already at E17.5. The analysis of knockout mice revealed that the loss of Uncx4.1 is accompanied with a 25% decrease in the population of mDA neurons, as marked by tyrosine hydroxylase (TH), dopamine transporter (DAT), Pitx3 and Ngn2. In contrast, the number of glutamatergic Pax6-positive cells was augmented, while the GABAergic neuron population appears not affected in Uncx4.1-deficient embryos.

Conclusion

We conclude that Uncx4.1 is implicated in the development of mDA neurons where it displays a unique temporal expression profile in the early postmitotic stage. Our data indicate that the mechanism underlying the role of Uncx4.1 in mDA development is likely related to differentiation processes in postmitotic stages, and where Ngn2 is engaged. Moreover, Uncx4.1 might play an important role during glutamatergic neuronal differentiation in the mouse midbrain.
Angiotensin II and III Metabolism and Effects on Steroid Production in the HAC15 Human Adrenocortical Cell Line
Authors: Oki Kenji , Kopf Phillip G. , Campbell William B. , Luis Lam Milay , Yamazaki Takeshi , Gomez-Sanchez Celso E. , Gomez-Sanchez Elise P.
Published: December 2012

Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex under primary regulation by the renin-angiotensin system. Angiotensin II (A-II) acts through the angiotensin types 1 and 2 receptors (AT1R and AT2R). A-II is metabolized in different tissues by various enzymes to generate two heptapeptides A-III and angiotensin 1-7, which can then be catabolized into smaller peptides. A-II was more potent than A-III in stimulating aldosterone secretion in the adrenocortical cell line HAC15, and A-II, but not A-III, stimulated cortisol secretion. A-II stimulated mRNA expression of steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2, whereas A-III stimulated 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2 but decreased the expression of CYP17A1 required for cortisol synthesis. The stimulation of aldosterone secretion by A-II and A-III was blocked by the AT1R receptor blocker, losartan, but not by an AT2R blocker. A-II was rapidly metabolized by the HAC15 cells to mainly to angiotensin 1-7, but not to A-III, and disappeared from the supernatant within 6 h. A-III was metabolized rapidly and disappeared within 1 h. In conclusion, A-II was not converted to A-III in the HAC15 cell and is the more potent stimulator of aldosterone secretion and cortisol of the two. A-III stimulated aldosterone secretion but not cortisol secretion.
PACAP Controls Adrenomedullary Catecholamine Secretion and Expression of Catecholamine Biosynthetic Enzymes at High Splanchnic Nerve Firing Rates Characteristic of Stress Transduction in Male Mice
Authors: Stroth N. , Kuri B. A. , Mustafa T. , Chan S.-A. , Smith C. B. , Eiden L. E.
Published: December 2012

The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a cotransmitter of acetylcholine at the adrenomedullary synapse, where autonomic regulation of hormone secretion occurs. We have previously reported that survival of prolonged metabolic stress in mice requires PACAP-dependent biosynthesis and secretion of adrenomedullary catecholamines (CAs). In the present experiments, we show that CA secretion evoked by direct high-frequency stimulation of the splanchnic nerve is abolished in native adrenal slices from male PACAP-deficient mice. Further, we demonstrate that PACAP is both necessary and sufficient for CA secretion ex vivo during stimulation protocols designed to mimic stress. In vivo, up-regulation of transcripts encoding adrenomedullary CA-synthesizing enzymes (tyrosine hydroxylase, phenylethanolamine N-methyltransferase) in response to both psychogenic and metabolic stressors (restraint and hypoglycemia) is PACAP-dependent. Stressor-induced alteration of the adrenomedullary secretory cocktail also appears to require PACAP, because up-regulation of galanin mRNA is abrogated in male PACAP-deficient mice. We further show that hypoglycemia-induced corticosterone secretion is not PACAP-dependent, ruling out the possibility that glucocorticoids are the main mediators of the aforementioned effects. Instead, experiments with bovine chromaffin cells suggest that PACAP acts directly at the level of the adrenal medulla. By integrating prolonged CA secretion, expression of biosynthetic enzymes and production of modulatory neuropeptides such as galanin, PACAP is crucial for adrenomedullary function. Importantly, our results show that PACAP is the dominant adrenomedullary neurotransmitter during conditions of enhanced secretory demand.
Synthesis of Poly(3,4-ethylenedioxythiophene)–Palladium Nanocomposite-coated Polymer Particles by Chemical Oxidative Seeded Dispersion Polymerization
Authors: Hamasaki Hiroyuki , Maekawa Yuya , Matsuzawa Soichiro , Ohtaka Atsushi , Nakamura Yoshinobu , Fujii Syuji
Published: December 2012

Poly(3,4-ethylenedioxythiophene)–palladium nanocomposite was deposited in situ from water-based solution onto micrometer-sized polystyrene particles. The resulting composite particles were extensively characterized with respect to particle size and size distribution, morphology, and chemical compositions.
Stereochemical Structure of the Complex of (−)-Epigallocatechin 3-Gallate and Caffeine
Authors: Tsutsumi Hiroyuki , Sato Takashi , Ishizu Takashi
Published: December 2012

Stereochemical structure of a 2:2 complex of (−)-epigallocatechin 3-gallate (EGCg) and caffeine, which was the main content of a crude precipitate formed by creaming, was determined by X-ray crystallographic analysis, and intermolecular interactions forming between EGCg and caffeine moieties were elucidated. Stereochemical structure and intermolecular interactions of a 2:2 complex of EGCg and nicotinamide was also determined.