bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac rupture following blunt trauma
Authors: Berg Regan , Talving Peep , Inaba Kenji
Published: October 2010

Cardiac rupture is the most extreme manifestation of blunt cardiac injury. In the first half of the 20th century this lesion was uniformly fatal. Since the first successful post-traumatic cardiorrhaphy by Desforges in 1955, multiple case reports and retrospective reviews have documented successful operative repair and survival of patients with this injury. Despite these successes, blunt cardiac rupture remains associated with a high mortality rate. The rarity of this condition and the heterogeneity of the literature make determination of exact epidemiologic data difficult. The classic clinical presentation is not universal and a subset of patients may present asymptomatically. Rapid transportation to medical care, accurate timely diagnosis and emergent operative intervention are essential for successful outcome. The use of ultrasonography in the trauma bay is a key component of early identification of these injuries. Specific outcome factors associated with survival are difficult to determine and even in those who survive to medical attention mortality rates remain as high as 60—90%.
Uncertainty and the problem of value: Consumers, culture and inequality in urban China
Authors: Hanser Amy
Published: October 2010

This article examines the divergent shopping patterns for consumers located in different positions within urban China’s social hierarchy. Drawing upon detailed ethnographic data, the article argues that differentiated class positions in urban China are expressed through the practicalities of daily shopping and consumer practices that involve fundamentally different ‘problems’ of uncertainty and value in the marketplace. It is shown that questions of social inequality are central to understanding not only marketplace behaviors, but also in drawing connections between markets and cultural logics of daily life.
A taste for greeting cards: Distinction within a denigrated cultural form
Authors: West Emily
Published: October 2010

Greeting cards are a denigrated product category in the USA, and yet consumers use them at high rates across taste formations. Consumers with relatively high cultural capital place a premium on originality in their self-expression, hence greeting cards present a consumption problem because they are a mode of expressing the self through mass-produced means. Based on interviews with 46 women, I show that consumers with higher cultural capital are more likely to prioritize card design over sentiment; select smaller, simpler designs and sentiments; prefer cards that are handmade, look handmade, or remind them of fine art; and are more likely to use cards ironically. In this way, consumers perform exclusivity through their taste, even through a form of mass culture. However, the social embeddedness of greeting card communication means that many consumers balance considerations of taste with the requirements of effective interpersonal communication. The ability to self-consciously modulate signifiers of taste is itself an indication of cultural knowledge and therefore of cultural capital.
Impact of the provision and timing of instructor-provided notes on university students’ learning
Authors: Raver Sharon A. , Maydosz Ann S.
Published: October 2010

Since the advent of PowerPoint and course delivery programs like Blackboard, more instructors in higher education are providing students with outlines of their lectures and expecting students to supplement these with their own notes. Although some have found that instructor-provided notes appear to enhance student learning, others suggest that students benefit from the act of taking detailed notes since it engages them in the learning process. While controlling for fidelity of lecture delivery, the present study examined the impact of three conditions on the posttest performance of 154 undergraduate and graduate students enrolled in an introductory special education course: (1) no instructor-provided notes were available, (2) instructor-provided notes were available immediately following lectures, and (3) instructor-provided notes were available before lectures. Analyses revealed that pretest scores were significantly correlated to posttest scores and that students who did not receive instructor-provided lecture notes received statistically significant lower posttest scores than students who received instructor-provided lecture notes before or after lectures. The implications for university instruction are discussed.
A first year experience of student-directed peer-assisted learning
Authors: Hammond John A. , Bithell Christine P. , Jones Lester , Bidgood Penelope
Published: October 2010

This study aimed to evaluate the implementation of a same-year peer-assisted learning (PAL) scheme, introduced in the first year of an undergraduate degree. The students participated in voluntary timetabled PAL sessions which encouraged a cooperative approach through student-directed activities. An action research design was used, and evaluation at each stage led to subsequent modifications over three years of implementation. Evaluation showed that the majority of students agreed that PAL helped with social aspects of learning but not that PAL contributed to improved study skills or assignment preparation. Between stages 1 and 2 small yet significant improvements in satisfaction occurred, and these continued in stage 3 when clearer guidance was provided. Based on our experience, PAL may provide effective learning environments; however, those interested in implementing it should be warned that it is not an easy option, and students need help to structure sessions effectively.
Lifestyle and Lung Health in Children and Adolescents: Children’s Way of Life and Their Respiratory Health
Authors: Carlsen Kai-Håkon
Published: October 2010

Our lifestyle is comprised of several different factors. The lifestyle pattern is set during childhood with a lasting effect upon adult lifestyle and later health. Several lifestyle factors may be modified including food, nutrition, physical activity and smoking. These are important for later health both in healthy children and in children with respiratory illness. The present editorial reflects upon the article by Roy J. Sheppard in the present issue of American Journal of Lifestyle in Medicine, taking up the influence of lifestyle factors on respiratory health in children. Physical activity is the primary factor in this context, relating both to healthy children and to children with chronic lung diseases. Physical activity is important for mastering of illness, and for some diseases even lifetime prognosis. Physical activity may increase the susceptibility to environmental exposures, such as environmental pollution and chlorine exposure in swimming pools. Limitations to physical activity may be set by chronic respiratory illness due to reduced baseline lung function, limiting increased ventilation levels during physical activity, and by exercise induced bronchoconstricion in asthma. Both aspects are important for treatment, habilitation and mastering of illness. Other aspects are fitness levels, overweight and impact upon quality of life and respiratory health. Regular physical training may be an important part of treatment strategies for respiratory diseases in children, and on the other hand, very heavy physical activity in adolescent top endurance athletes may lead to bronchial hyperresponsiveness and exercise induced asthma. The problem is complex deserving careful consideration.
The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy
Authors: Hsu Andy K. , Quach Hang , Tai Tsin , Prince H. Miles , Harrison Simon J. , Trapani Joseph A. , Smyth Mark J. , Neeson Paul , Ritchie David S.
Published: October 2010

Lenalidomide combined with dexamethasone is an effective treatment for refractory/relapsed multiple myeloma (MM). Lenalidomide stimulates natural killer (NK) cells and enhances antitumor responses. We assessed NK cell number and function in 25 patients with MM participating in a clinical trial of lenalidomide and dexamethasone. NK cell numbers increased from a mean of 2.20 ± 0.05 × 105/mL (baseline) to a mean of 3.90 ± 0.03 × 105/mL (cycle 6; P = .05); however, in vitro NK-cell–mediated cytotoxicity decreased from 48.9% ± 6.8% to 27.6% ± 5.1% (P = .0028) and could not be rescued by lenalidomide retreatment. Lenalidomide increased normal donor NK-cell cytotoxicity in vitro from 38.5% to 53.3%, but this was completely abrogated by dexamethasone. Dexamethasone suppression of NK cell–mediated cytotoxicity was partially reversed by a 3-day washout, but these cells remained refractory to lenalidomide-induced enhanced function. Lymphocyte subset depletion experiments revealed that lenalidomide's enhancement of NK cell–mediated cytotoxicity was mediated by CD4+ T-cell production of interleukin 2 and that dexamethasone acted by suppressing interleukin-2 production. Similarly, the reduced ability of NK cells from patients with MM to respond to lenalidomide was also due to impaired CD4 T-cell function. Our findings indicate that lenalidomide immunostimulatory effects on patient NK cells are severely blunted by concurrent dexamethasone administration.
Confronting two-pair primer design for enzyme-free SNP genotyping based on a genetic algorithm
Authors: Yang Cheng-Hong , Cheng Yu-Huei , Chuang Li-Yeh , Chang Hsueh-Wei
Published: October 2010

Background

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method produces allele-specific DNA bands of different lengths by adding four designed primers and it achieves the single nucleotide polymorphism (SNP) genotyping by electrophoresis without further steps. It is a time- and cost-effective SNP genotyping method that has the advantage of simplicity. However, computation of feasible CTPP primers is still challenging.

Results

In this study, we propose a GA (genetic algorithm)-based method to design a feasible CTPP primer set to perform a reliable PCR experiment. The SLC6A4 gene was tested with 288 SNPs for dry dock experiments which indicated that the proposed algorithm provides CTPP primers satisfied most primer constraints. One SNP rs12449783 in the SLC6A4 gene was taken as an example for the genotyping experiments using electrophoresis which validated the GA-based design method as providing reliable CTPP primer sets for SNP genotyping.

Conclusions

The GA-based CTPP primer design method provides all forms of estimation for the common primer constraints of PCR-CTPP. The GA-CTPP program is implemented in JAVA and a user-friendly input interface is freely available at http://bio.kuas.edu.tw/ga-ctpp/.
House mouse colonization patterns on the sub-Antarctic Kerguelen Archipelago suggest singular primary invasions and resilience against re-invasion
Authors: Hardouin Emilie A , Chapuis Jean-Louis , Stevens Mark I , van Vuuren Jansen Bettine , Quillfeldt Petra , Scavetta Rick J , Teschke Meike , Tautz Diethard
Published: October 2010

Background

Starting from Western Europe, the house mouse (Mus musculus domesticus) has spread across the globe in historic times. However, most oceanic islands were colonized by mice only within the past 300 years. This makes them an excellent model for studying the evolutionary processes during early stages of new colonization. We have focused here on the Kerguelen Archipelago, located within the sub-Antarctic area and compare the patterns with samples from other Southern Ocean islands.

Results

We have typed 18 autosomal and six Y-chromosomal microsatellite loci and obtained mitochondrial D-loop sequences for a total of 534 samples, mainly from the Kerguelen Archipelago, but also from the Falkland Islands, Marion Island, Amsterdam Island, Antipodes Island, Macquarie Island, Auckland Islands and one sample from South Georgia. We find that most of the mice on the Kerguelen Archipelago have the same mitochondrial haplotype and all share the same major Y-chromosomal haplotype. Two small islands (Cochons Island and Cimetière Island) within the archipelago show a different mitochondrial haplotype, are genetically distinct for autosomal loci, but share the major Y-chromosomal haplotype. In the mitochondrial D-loop sequences, we find several single step mutational derivatives of one of the major mitochondrial haplotypes, suggesting an unusually high mutation rate, or the occurrence of selective sweeps in mitochondria.

Conclusions

Although there was heavy ship traffic for over a hundred years to the Kerguelen Archipelago, it appears that the mice that have arrived first have colonized the main island (Grande Terre) and most of the associated small islands. The second invasion that we see in our data has occurred on islands that are detached from Grande Terre and were likely to have had no resident mice prior to their arrival. The genetic data suggest that the mice of both primary invasions originated from related source populations. Our data suggest that an area colonized by mice is refractory to further introgression, possibly due to fast adaptations of the resident mice to local conditions.
Involvement of EupR, a response regulator of the NarL/FixJ family, in the control of the uptake of the compatible solutes ectoines by the halophilic bacterium Chromohalobacter salexigens
Authors: Rodríguez-Moya Javier , Argandoña Montserrat , Reina-Bueno Mercedes , Nieto Joaquín J , Iglesias-Guerra Fernando , Jebbar Mohamed , Vargas Carmen
Published: October 2010

Background

Osmosensing and associated signal transduction pathways have not yet been described in obligately halophilic bacteria. Chromohalobacter salexigens is a halophilic bacterium with a broad range of salt tolerance. In response to osmotic stress, it synthesizes and accumulates large amounts of the compatible solutes ectoine and hydroxyectoine. In a previous work, we showed that ectoines can be also accumulated upon transport from the external medium, and that they can be used as carbon sources at optimal, but not at low salinity. This was related to an insufficient ectoine(s) transport under these conditions.

Results

A C. salexigens Tn1732-induced mutant (CHR95) showed a delayed growth with glucose at low and optimal salinities, could not grow at high salinity, and was able to use ectoines as carbon sources at low salinity. CHR95 was affected in the transport and/or metabolism of glucose, and showed a deregulated ectoine uptake at any salinity, but it was not affected in ectoine metabolism. Transposon insertion in CHR95 caused deletion of three genes, Csal0865-Csal0867: acs, encoding an acetyl-CoA synthase, mntR, encoding a transcriptional regulator of the DtxR/MntR family, and eupR, encoding a putative two-component response regulator with a LuxR_C-like DNA-binding helix-turn-helix domain. A single mntR mutant was sensitive to manganese, suggesting that mntR encodes a manganese-dependent transcriptional regulator. Deletion of eupR led to salt-sensitivity and enabled the mutant strain to use ectoines as carbon source at low salinity. Domain analysis included EupR as a member of the NarL/FixJ family of two component response regulators. Finally, the protein encoded by Csal869, located three genes downstream of eupR was suggested to be the cognate histidine kinase of EupR. This protein was predicted to be a hybrid histidine kinase with one transmembrane and one cytoplasmic sensor domain.

Conclusions

This work represents the first example of the involvement of a two-component response regulator in the osmoadaptation of a true halophilic bacterium. Our results pave the way to the elucidation of the signal transduction pathway involved in the control of ectoine transport in C. salexigens.
Transplanted bone marrow stem cells relocate to infarct penumbra and co-express endogenous proliferative and immature neuronal markers in a mouse model of ischemic cerebral stroke
Authors: Zhang Xue-mei , Du Fang , Yang Dan , Yu Chun-jiang , Huang Xiang-nan , Liu Wei , Fu Jin
Published: October 2010

Background

Several studies demonstrate that neurogenesis may be induced or activated following vascular insults, which may be important for neuronal regeneration and functional recovery. Understanding the cellular mechanism underlying stroke-associated neurogenesis is of neurobiological as well as neurological/clinical relevance. The present study attempted to explore potential homing and early development of transplanted bone marrow stem cells in mouse forebrain after focal occlusion of the middle cerebral artery, an experimental model of ischemic stroke.

Results

Bone marrow stem cells isolated from donor mice were confirmed by analysis of surface antigen profile, and were pre-labeled with a lipophilic fluorescent dye PKH26, and subsequently transfused into recipient mice with middle cerebral artery coagulation. A large number of PKH26-labeled cells were detected surrounding the infarct site, most of which colocalized with immunolabelings for the proliferating cell nuclear antigen (PCNA) and some also colocalized with the immature neuronal marker doublecortin (DCX) during 1-2 weeks after the bone marrow cells transfusion.

Conclusions

The present study shows that transplanted bone morrow cells largely relocate to the infarct penumbra in ischemic mouse cerebrum. These transplanted bone marrow cells appear to undergo a process of in situ proliferation and develop into putative cortical interneurons during the early phase of experimental vascular injury.
IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma
Authors: White Colin D , Khurana Hema , Gnatenko Dmitri V , Li Zhigang , Odze Robert D , Sacks David B , Schmidt Valentina A
Published: October 2010

Background

IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC.

Methods

IQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of theIqgap2promoter was determined by pyrosequencing of bisulfite-treated genomic DNA.

Results

IQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although theIqgap2promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6).

Conclusions

We conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of theIqgap2promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report
Authors: Rodríguez-Martínez Ana B , Garrido Joseba M , Zarranz Juan J , Arteagoitia Jose M , de Pancorbo Marian M , Atarés Begoña , Bilbao Miren J , Ferrer Isidro , Juste Ramón A
Published: October 2010

Background

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion.

Case presentation

We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine.

Conclusions

A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.
Cardiovascular risk estimated after 13 years of follow-up in a low-incidence Mediterranean region with high-prevalence of cardiovascular risk factors
Authors: Huerta José M , Tormo María-José , Gavrila Diana , Navarro Carmen
Published: October 2010

Background

Murcia (south-east Spain) shows increased cardiovascular (CV) morbimortality as compared to other Spanish regions. Our objective was to assess the CV risk associated with major risk factors (RF) among adult population of Murcia.

Methods

A cohort of 2314 subjects (18-70 years) with full biochemical and questionnaire data was followed-up for 13 years. Incident cases of ischemic heart disease and stroke were identified by record linkage, individual questionnaires and revision of medical records. Relative risks were obtained by multivariate Cox regression stratified by age and sex, and ischemic risk attributable to CVRF was calculated.

Results

After more than 26276 person-years of follow-up, 57 incident ischemic events (77% men) and 37 stroke cases (62% men) were identified. Independent risk factors of ischemic heart disease (IHD) and all CV events combined, with RR ranging from 1.6 to 2.6, were total serum cholesterol ≥ 240 mg/dl (HR = 2.6, 95%CI:1.3-5.1), blood pressure levels ≥ 140/90 mmHg (HR = 2.6, 95%CI:1.4-4.8), ever tobacco smoking (HR = 2.2; 95%CI:1.1-4.5), and diabetes (HR = 2.0; 95%CI: 1.0-3.8). No increased CV risk was detected for known participants under treatment who showed cholesterol and blood pressure values below the clinical risk threshold. Smoking was significantly associated with stroke. For all events combined, the major risk factors were hypercholesterolemia, hypertension and ever use of tobacco. Despite its high prevalence, obesity was not associated to CV risk. Most of the IHD cases were attributable to smoking (44%), hypertension (38%) and hypercholesterolemia (26%).

Conclusions

In the Region of Murcia, smoking accounted for the largest proportion of cardiovascular risk, whereas hypertension displaced hypercholesterolemia as the second leading cause of CV disease. Our study deepens in our understanding of the cardiovascular epidemiology in Spanish areas of Mediterranean Europe with relatively high cardiovascular morbimortality, that are poorly represented by the available risk equations.
Socioeconomic status and duration and pattern of sickness absence. A 1-year follow-up study of 2331 hospital employees
Authors: Kristensen Trine R , Jensen Signe M , Kreiner Svend , Mikkelsen Sigurd
Published: October 2010

Background

Sickness absence increases with lower socioeconomic status. However, it is not well known how this relation depends on specific aspects of sickness absence or the degree to which socioeconomic differences in sickness absence may be explained by other factors.

The purpose of the study was to examine differences in sickness absence among occupational groups in a large general hospital; how they depend on combinations of frequency and duration of sickness absence spells; and if they could be explained by self-reported general health, personal factors and work factors.

Methods

The design is a 1-year prospective cohort study of 2331 hospital employees. Baseline information include job title, work unit, perceived general health, work factors and personal factors recorded from hospital administrative files or by questionnaire (response rate 84%). Sickness absence during follow-up was divided into short (1-3 days), medium (4-14 days) and long (>14 days) spells, and into no absence, "normal" absence (1-3 absences of certain durations) and "abnormal" absence (any other absence than "normal"). Socioeconomic status was assessed by job titles grouped in six occupational groups by level of education (from doctors to cleaners/porters). Effects of occupational group on sickness absence were adjusted for significant effects of age, gender, general health, personal factors and work factors. We used Poisson or logistic regression analysis to estimate the effects of model covariates (rate ratios (RR) or odds ratios (OR)) and their 95% confidence intervals (CI).

Results

With a few exceptions sickness absence increased with decreasing socioeconomic status. However, the social gradient was quite different for different types of sickness absence. The gradient was strong for medium spells and "abnormal" absence, and weak for all spells, short spells, long spells and "normal" absence. For cleaners compared to doctors the adjusted risk estimates increased 4.2 (95% CI 2.8-6.2) and 7.4 (95% CI 3.3-16) times for medium spells and "abnormal" absence, respectively, while the similar changes varied from 0.79 to 2.8 for the other absence outcomes. General health explained some of the social gradient. Work factors and personal factors did not.

Conclusions

The social gradient in sickness absence was different for absences of different duration and patterns. It was strongest for absences of medium length and "abnormal" absence. The social gradient was not explained by other factors.
Smoking reduces surfactant protein D and phospholipids in patients with and without chronic obstructive pulmonary disease
Authors: Moré Jayaji M , Voelker Dennis R , Silveira Lori J , Edwards Michael G , Chan Edward D , Bowler Russell P
Published: October 2010

Background

Pulmonary surfactant D (SP-D) has important regulatory functions for innate immunity and has been implicated as a biomarker for chronic obstructive pulmonary disease (COPD). We hypothesized that COPD patients would have reduced bronchoalveolar lavage (BAL) fluid SP-D levels compared to healthy smoking and non-smoking controls.

Methods

BAL SP-D and phospholipids were quantified and corrected for dilution in 110 subjects (65 healthy never smokers, 23 smokers with normal spirometry, and 22 smokers with COPD).

Results

BAL SP-D was highest in never smokers (mean 51.9 μg/mL ± 7.1 μg/mL standard error) compared to both smokers with normal spirometry (16.0 μg/mL ± 11.8 μg/mL) and subjects with COPD (19.1 μg/mL ± 12.9 μg/mL; P < 0.0001). Among smokers with COPD, BAL SP-D correlated significantly with FEV1% predicted (R = 0.43; P < 0.05); however, the strongest predictor of BAL SP-D was smoking status. BAL SP-D levels were lowest in current smokers (12.8 μg/mL ± 11.0 μg/mL), intermediate in former smokers (25.2 μg/mL ± 14.2 μg/mL; P < 0.008), and highest in never smokers. BAL phospholipids were also lowest in current smokers (6.5 nmol ± 1.5 nmol), intermediate in former smokers (13.1 nmol ± 2.1 nmol), and highest in never smokers (14.8 nmol ± 1.1 nmol; P < 0.0001).

Conclusions

These data suggest that smokers, and especially current smokers, exhibit significantly reduced BAL SP-D and phospholipids compared to nonsmokers. Our findings may help better explain the mechanism that leads to the rapid progression of disease and increased incidence of infection in smokers.
Variability of indication criteria in knee and hip replacement: an observational study
Authors: Cobos Raquel , Latorre Amaia , Aizpuru Felipe , Guenaga Jose I , Sarasqueta Cristina , Escobar Antonio , García Lidia , Herrera-Espiñeira Carmen
Published: October 2010

Background

Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication.

Methods

The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated.

The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity.

Results

The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate.

Conclusions

A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates.
Genome-wide identification of Saccharomyces cerevisiae genes required for tolerance to acetic acid
Authors: Mira Nuno P , Palma Margarida , Guerreiro Joana F , Sá-Correia Isabel
Published: October 2010

Background

Acetic acid is a byproduct ofSaccharomyces cerevisiaealcoholic fermentation. Together with high concentrations of ethanol and other toxic metabolites, acetic acid may contribute to fermentation arrest and reduced ethanol productivity. This weak acid is also a present in lignocellulosic hydrolysates, a highly interesting non-feedstock substrate in industrial biotechnology. Therefore, the better understanding of the molecular mechanisms underlyingS. cerevisiaetolerance to acetic acid is essential for the rational selection of optimal fermentation conditions and the engineering of more robust industrial strains to be used in processes in which yeast is explored as cell factory.

Results

The yeast genes conferring protection against acetic acid were identified in this study at a genome-wide scale, based on the screening of the EUROSCARF haploid mutant collection for susceptibility phenotypes to this weak acid (concentrations in the range 70-110 mM, at pH 4.5). Approximately 650 determinants of tolerance to acetic acid were identified. Clustering of these acetic acid-resistance genes based on their biological function indicated an enrichment of genes involved in transcription, internal pH homeostasis, carbohydrate metabolism, cell wall assembly, biogenesis of mitochondria, ribosome and vacuole, and in the sensing, signalling and uptake of various nutrients in particular iron, potassium, glucose and amino acids. A correlation between increased resistance to acetic acid and the level of potassium in the growth medium was found. The activation of the Snf1p signalling pathway, involved in yeast response to glucose starvation, is demonstrated to occur in response to acetic acid stress but no evidence was obtained supporting the acetic acid-induced inhibition of glucose uptake.

Conclusions

Approximately 490 of the 650 determinants of tolerance to acetic acid identified in this work are implicated, for the first time, in tolerance to this weak acid. These are novel candidate genes for genetic engineering to obtain more robust yeast strains against acetic acid toxicity. Among these genes there are number of transcription factors that are documented regulators of a large percentage of the genes found to exert protection against acetic acid thus being considered interesting targets for subsequent genetic engineering. The increase of potassium concentration in the growth medium was found to improve the expression of maximal tolerance to acetic acid, consistent with the idea that the adequate manipulation of nutrient concentration of industrial growth medium can be an interesting strategy to surpass the deleterious effects of this weak acid in yeast cells.
Factors determining anti-malarial drug use in a peri-urban population from malaria holoendemic region of western kenya
Authors: Watsierah Carren A , Jura Walter GZO , Oyugi Henry , Abong'o Benard , Ouma Collins
Published: October 2010

Background

Interventions to reverse trends in malaria-related morbidity and mortality in Kenya focus on preventive strategies and drug efficacy. However, the pattern of use of anti-malarials in malaria-endemic populations, such as in western Kenya, is still poorly understood. It is critical to understand the patterns of anti-malarial drug use to ascertain that the currently applied new combination therapy to malaria treatment, will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine the patterns of use of anti-malarial drugs in households (n = 397) in peri-urban location of Manyatta-B sub-location in Kisumu in western Kenya.

Methods

Household factors, associated with the pattern of anti-malarials use, were evaluated. Using clusters, questionnaire was administered to a particular household member who had the most recent malaria episode (within <2 weeks) and used an anti-malarial for cure. Mothers/caretakers provided information for children aged <13 years.

Results

Stratification of the type of anti-malarial drugs taken revealed that 37.0% used sulphadoxine/pyrimethamine (SP), 32.0% artemisinin-based combined therapy (ACT), 11.1% anti-pyretics, 7.3% chloroquine (CQ), 7.1% quinine, 2.5% amodiaquine (AQ), while 3.0% used others which were perceived as anti-malarials (cough syrups and antibiotics). In a regression model, it was demonstrated that age (P = 0.050), household size (P = 0.047), household head (P = 0.049), household source of income (P = 0.015), monthly income (P = 0.020), duration of use (P = 0.029), dosage of drugs taken (P = 0.036), and source of drugs (P = 0.005) significantly influenced anti-malarial drug use. Overall, 38.8% of respondents used drugs as recommended by the Ministry of Health.

Conclusion

This study demonstrates that consumers require access to correct and comprehensible information associated with use of drugs, including self-prescription. There is potential need by the Kenyan government to improve malaria care and decrease malaria-related morbidity and mortality by increasing drug affordability, ensuring that the recommended anti-malarial drugs are easily available in all government approved drug outlets and educates the local shopkeepers on the symptoms and appropriate treatment of malaria. Following a switch to ACT in national drug policy, education on awareness and behaviour change is recommended, since the efficacy of ACT alone is not sufficient to reduce morbidity and mortality due to malaria.
Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections
Authors: Olesen Cathrine Holm , Brahimi Karima , Vandahl Brian , Lousada-Dietrich Susana , Jogdand Prajakta S , Vestergaard Lasse S , Dodoo Daniel , Højrup Peter , Christiansen Michael , Larsen Severin Olesen , Singh Subhash , Theisen Michael
Published: October 2010

Background

In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological studies have indicated an association of cytophilic anti-parasite IgG with protection against malaria. It has been hypothesized that the initial antibody responses against parasite antigens upon first few Plasmodium falciparum infections is dominated by non-protective IgG2/IgG4 and IgM antibodies, which then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies.

Methods

Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P. falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high molecular weight (≥ 70 kDa) or low molecular weight (< 70 kDa). The number of discernable low molecular weight parasite antigens detected by different IgG subclass antibodies from each plasma sample was recorded. Using Wilcoxons rank sum test these reactivities were compared amongst groups of individuals with different levels of exposure to P. falciparum infections.

Results

IgG4 and IgM antibodies in plasma samples from all groups detected very few parasite antigens. IgG2 antibodies from all groups detected a common pattern of high molecular weight parasite antigens. Cytophilic IgG subclasses in plasma samples from individuals with higher levels of exposure to P. falciparum infections distinctly detected higher numbers of low molecular weight parasite antigens.

Conclusions

In the present study, there was no evidence for switching of antibody responses from non-cytophilic to cytophilic subclasses against blood-stage parasite antigens as a likely mechanism for induction of protective immunity against malaria.
Intracellular expression of IRF9 Stat fusion protein overcomes the defective Jak-Stat signaling and inhibits HCV RNA replication
Authors: Poat Bret , Hazari Sidhartha , Chandra Partha K , Gunduz Feyza , Alvarez Xavier , Balart Luis A , Garry Robert F , Dash Srikanta
Published: October 2010

Interferon alpha (IFN-α) binds to a cell surface receptor that activates the Jak-Stat signaling pathway. A critical component of this pathway is the translocation of interferon stimulated gene factor 3 (a complex of three proteins Stat1, Stat2 and IRF9) to the nucleus to activate antiviral genes. A stable sub-genomic replicon cell line resistant to IFN-α was developed in which the nuclear translocation of Stat1 and Stat2 proteins was prevented due to the lack of phosphorylation; whereas the nuclear translocation of IRF9 protein was not affected. In this study, we sought to overcome defective Jak-Stat signaling and to induce an antiviral state in the IFN-α resistant replicon cell line by developing a chimera IRF9 protein fused with the trans activating domain (TAD) of either a Stat1 (IRF9-S1C) or Stat2 (IRF9-S2C) protein. We show here that intracellular expression of fusion proteins using the plasmid constructs of either IRF9-S1C or IRF9-S2C, in the IFN-α resistant cells, resulted in an increase in Interferon Stimulated Response Element (ISRE) luciferase promoter activity and significantly induced HLA-1 surface expression. Moreover, we show that transient transfection of IRF9-S1C or IRF9-S2C plasmid constructs into IFN-α resistant replicon cells containing sub-genomic HCV1b and HCV2a viruses resulted in an inhibition of viral replication and viral protein expression independent of IFN-α treatment. The results of this study indicate that the recombinant fusion proteins of IRF9-S1C, IRF9-S2C alone, or in combination, have potent antiviral properties against the HCV in an IFN-α resistant cell line with a defective Jak-Stat signaling.
Aquaporin 1, a Potential Therapeutic Target for Migraine with Aura
Authors: Xu Guang-Yin , Wang Fen , Jiang Xinghong , Tao Jin
Published: October 2010

The pathophysiology of migraine remains largely unknown. However, evidence regarding the molecules participating in the pathophysiology of migraine has been accumulating. Water channel proteins, known as aquaporins (AQPs), notably AQP-1 and AQP-4, appears to be involved in the pathophysiology of several neurological diseases. This review outlines newly emerging evidence indicating that AQP-1 plays an important role in pain signal transduction and migraine and could therefore serve as a potential therapeutic target for these diseases.
Clinical Implications of the Cancer Genome
Authors: MacConaill Laura E. , Garraway Levi A.
Published: October 2010

Cancer is a disease of the genome. Most tumors harbor a constellation of structural genomic alterations that may dictate their clinical behavior and treatment response. Whereas elucidating the nature and importance of these genomic alterations has been the goal of cancer biologists for several decades, ongoing global genome characterization efforts are revolutionizing both tumor biology and the optimal paradigm for cancer treatment at an unprecedented scope. The pace of advance has been empowered, in large part, through disruptive technological innovations that render complete cancer genome characterization feasible on a large scale. This article highlights cardinal biologic and clinical insights gleaned from systematic cancer genome characterization. We also discuss how the convergence of cancer genome biology, technology, and targeted therapeutics articulates a cohesive framework for the advent of personalized cancer medicine.
American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer
Authors: Rizzo J. Douglas , Brouwers Melissa , Hurley Patricia , Seidenfeld Jerome , Arcasoy Murat O. , Spivak Jerry L. , Bennett Charles L. , Bohlius Julia , Evanchuk Darren , Goode Matthew J. , Jakubowski Ann A. , Regan David H. , Somerfield Mark R.
Published: October 2010

Purpose

To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

Methods

An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.

Results

The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.

Recommendations

For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration–approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the American Society of Hematology and has been published jointly by invitation and consent in both Journal of Clinical Oncology and Blood. Copyright © 2010 American Society of Clinical Oncology and American Society of Hematology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology or the American Society of Hematology.