bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Perceived Teacher Support and Its Influence on Adolescent Career Development
Authors: Metheny Jennifer , McWhirter Ellen Hawley , O'Neil Maya Elin
Published: January 2008

This article examines available measures of perceived teacher support and presents findings from two studies exploring the psychometric properties of the Teacher Support Scale (TSS). In Study 1, an exploratory factor analysis suggested a hierarchical structure with four first-order factors (Invested, Positive Regard, Expectations, and Accessible subscales) loading onto a single, higher order factor, excellent reliability, and concurrent validity. Perceived teacher support was significantly correlated with career decision-making self-efficacy and vocational outcome expectations. In Study 2, a confirmatory factor analysis did not provide replication of the initial model in a separate sample. However, the four, first-order factors explained a statistically significant amount of the variance in question items, and support was provided for their strong relationship to a single, higher order construct of teacher support. Recommendations for future practice and research on the role of teacher support in adolescent career development and suggestions for modifications to the measure are provided.
Are There Differential Effects of Managed Care on Publicly Insured Children With Chronic Health Conditions?
Authors: Davidoff Amy , Hill Ian , Courtot Brigette , Adams Emerald
Published: January 2008

The authors use variation across states and over time in managed care (MC) programs for publicly insured children to examine whether effects differ for children with chronic health conditions (CWCHC) and those without. The authors pool data from the 1997 to 2002 National Health Interview Survey and link county, year, and health status information on type of MC programs implemented. Findings show that the effects of MC are concentrated on CWCHC and that CWCHC experience reductions in use of specialist, mental health, and prescription drugs. Capitated programs with mental health or specialty carve-outs are associated with a greater number and larger decreases in service use compared to integrated capitated programs. While it is not possible to determine whether MC programs resulted in more appropriate use of services, corresponding reductions in perceived access were not observed, suggesting that net effects of MC on service use represent improvements in care coordination.
Hospital Responses to the Leapfrog Group in Local Markets
Authors: Scanlon Dennis P. , Christianson Jon B. , Ford Eric W.
Published: January 2008

The Leapfrog (LF) initiative, directed at improving patient safety in hospitals, may be the most ambitious, coordinated attempt to date on the part of large employers to shape the delivery of health care in America. This article assesses the role of market conditions and other factors in influencing hospital responses to LF activities at the community level. Community characteristics were found to be important in explaining hospital participation in a LF safety standards survey at the study sites. However, characteristics of the individual hospitals, and of the LF goals themselves, were more important in explaining the relatively limited progress by hospitals across all sites in achieving those goals over a 5-year period.
Look Back in Anger?
Authors: Cohen-Marks Mara , Nuño Stephen A. , Sanchez Gabriel R.
Published: January 2008

In the spring of 2006, an unprecedented mobilization of undocumented immigrants and their advocates sent shockwaves across the U.S. political landscape. Whether the demonstrations did more to advance the interests of undocumented residents and other immigrants or to harden nativist sentiments remains an open question. Examining data culled from a three-county exit poll of more than 4,300 voters in three urbanized western counties, we employ multivariate analysis to examine how the immigration rallies impacted voters' perceptions of Mexican immigrants. Our results indicate that the demonstrators failed to win the hearts and minds of American voters, most of whom reported that the rallies tended to negatively impact their perceptions of Mexican immigrants. The depth of this negative reaction varied across the sociopolitical contexts represented by the three counties as well as voters' individual attributes including party identification, ethnicity, nativity, and other characteristics.
A Mindfulness-Based Health Wellness Program for Managing Morbid Obesity
Authors: Singh Nirbhay N. , Lancioni Giulio E. , Singh Ashvind N. , Winton Alan S. W. , Singh Judy , McAleavey Kristen M. , Adkins Angela D. , Joy Subhashni D. S.
Published: January 2008

There are numerous methods for reducing obesity; however, often none of these methods prove effective for specific individuals. For individuals who have failed on specific diets and other weight loss programs, finding a good match between their needs and an effective method is often difficult. The authors collaboratively developed a multicomponent mindfulness-based health wellness program with an individual who was morbidly obese and wanted a lifestyle change. The components included physical exercise, a food awareness program, mindful eating to manage rapid eating, visualizing and labeling hunger, and a mindfulness procedure as a self-control strategy. The individual reduced his weight from 315 pounds to 171 pounds, increased his physical activity, ate healthy foods, stopped eating rapidly, substantially reduced serious medical risk factors, eliminated physical discomfort and mobility problems due to his weight, and enhanced his lifestyle over almost a 5-year period. He maintained his health wellness during 12 months of follow-up.
The Emergence of Growth Management Planning in the United States: The Case of Golden v. Planning Board of Town of Ramapo and Its Aftermath
Authors: Meck Stuart , Retzlaff Rebecca
Published: January 2008

The modern growth management movement in the United States solidly emerged with the 1972 decision of the New York Court of Appeals, the state's highest court, in Golden v. Planning Board of Town of Ramapo. Here, the court upheld a phased development timing ordinance in which the approval of a special permit for residential development was linked to the provision of public infrastructure in accordance with an 18-year capital improvement program. This article examines how the Ramapo officials proceeded, the circumstances in which they operated, the resulting litigation, and the aftermath. It contends that, despite its influence on planning law and practice, the Ramapo system still had significant problems as an instrument of modern planning policy, creating a sprawling development pattern that is often viewed as exclusionary in places with few development options.
COPD diagnosis related to different guidelines and spirometry techniques
Authors: Nathell Lennart , Nathell Madelene , Malmberg Per , Larsson Kjell
Published: January 2008

The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC).

In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks. Those who smoked more than 8 cigarettes per day were invited to perform a spirometry.

Totally 3,887 spirometries were performed. In this sample 10.2% fulfilled the NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria. The diagnosis according to NICE and GOLD guidelines is based on FVC and in the ERS guidelines the best value of either SVC or FVC is used. Thus, substantially more subjects with COPD were found when the best of either SVC or FVC was used. Forced VC tended to be higher than SVC when lung function was normal and in those with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after bronchodilatation in those who had severe bronchial obstruction.

The diagnosis of COPD is highly depending on which guidelines are used for defining the disease. If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis will be missed in a substantial number of patients.
Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study
Authors: Sims Michael W , Tal-Singer Ruth M , Kierstein Sonja , Musani Ali I , Beers Michael F , Panettieri Reynold A , Haczku Angela
Published: January 2008

Background

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.

Methods

We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studiedin vitrousing an established model of isolated type II alveolar epithelial cell culture.

Results

Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.

Conclusion

Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cellsin vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.
Gene function prediction using labeled and unlabeled data
Authors: Zhao Xing-Ming , Wang Yong , Chen Luonan , Aihara Kazuyuki
Published: January 2008

Background

In general, gene function prediction can be formalized as a classification problem based on machine learning technique. Usually, both labeled positive and negative samples are needed to train the classifier. For the problem of gene function prediction, however, the available information is only about positive samples. In other words, we know which genes have the function of interested, while it is generally unclear which genes do not have the function, i.e. the negative samples. If all the genes outside of the target functional family are seen as negative samples, the imbalanced problem will arise because there are only a relatively small number of genes annotated in each family. Furthermore, the classifier may be degraded by the false negatives in the heuristically generated negative samples.

Results

In this paper, we present a new technique, namely Annotating Genes with Positive Samples (AGPS), for defining negative samples in gene function prediction. With the defined negative samples, it is straightforward to predict the functions of unknown genes. In addition, the AGPS algorithm is able to integrate various kinds of data sources to predict gene functions in a reliable and accurate manner. With the one-class and two-class Support Vector Machines as the core learning algorithm, the AGPS algorithm shows good performances for function prediction on yeast genes.

Conclusion

We proposed a new method for defining negative samples in gene function prediction. Experimental results on yeast genes show that AGPS yields good performances on both training and test sets. In addition, the overlapping between prediction results and GO annotations on unknown genes also demonstrates the effectiveness of the proposed method.
Independent Origins of New Sex-Linked Chromosomes in the melanica and robusta Species Groups of Drosophila
Authors: Flores Sergio V , Evans Amy L , McAllister Bryant F
Published: January 2008

Background

Recent translocations of autosomal regions to the sex chromosomes represent important systems for identifying the evolutionary forces affecting convergent patterns of sex-chromosome heteromorphism. Additions to the sex chromosomes have been reported in the melanica and robusta species groups, two sister clades of Drosophila. The close relationship between these two species groups and the similarity of their rearranged karyotypes motivates this test of alternative hypotheses; the rearranged sex chromosomes in both groups are derived through a common origin, or the rearrangements are derived through at least two independent origins. Here we examine chromosomal arrangement in representatives of the melanica and the robusta species groups and test these alternative hypotheses using a phylogenetic approach.

Results

Two mitochondrial and two nuclear gene sequences were used to reconstruct phylogenetic relationships of a set of nine ingroup species having fused and unfused sex chromosomes and representing a broad sample of both species groups. Different methods of phylogenetic inference, coupled with concurrent cytogenetic analysis, indicate that the hypothesis of independent origins of rearranged sex chromosomes within each species group is significantly more likely than the alternative hypothesis of a single common origin. An estimate tightly constrained around 8 My was obtained for the age of the rearranged sex chromosomes in the melanica group; however, a more loosely constrained estimate of 10–15 My was obtained for the age of the rearrangement in the robusta group.

Conclusion

Independent acquisition of new chromosomal arms by the sex chromosomes in the melanica and robusta species groups represents a case of striking convergence at the karyotypic level. Our findings indicate that the parallel divergence experienced by newly sex-linked genomic regions in these groups represents an excellent system for studying the tempo of sex chromosome evolution.
Genome-wide analysis of CCCH zinc finger family in Arabidopsis and rice
Authors: Wang Dong , Guo Yinghui , Wu Changai , Yang Guodong , Li Yingying , Zheng Chengchao
Published: January 2008

Background

Genes in the CCCH family encode zinc finger proteins containing the motif with three cysteines and one histidine residues. They have been known to play important roles in RNA processing as RNA-binding proteins in animals. To date, few plant CCCH proteins have been studied functionally.

Results

In this study, a comprehensive computational analysis identified 68 and 67 CCCH family genes in Arabidopsis and rice, respectively. A complete overview of this gene family in Arabidopsis was presented, including the gene structures, phylogeny, protein motifs, and chromosome locations. In addition, a comparative analysis between these genes in Arabidopsis and rice was performed. These results revealed that the CCCH families in Arabidopsis and rice were divided into 11 and 8 subfamilies, respectively. The gene duplication contributed to the expansion of the CCCH gene family in Arabidopsis genome. Expression studies indicated that CCCH proteins exhibit a variety of expression patterns, suggesting diverse functions. Finally, evolutionary analysis showed that one subfamily is higher plant specific. The expression profile indicated that most members of this subfamily are regulated by abiotic or biotic stresses, suggesting that they could have an effective role in stress tolerance.

Conclusion

Our comparative genomics analysis of CCCH genes and encoded proteins in two model plant species provides the first step towards the functional dissection of this emerging family of potential RNA-binding proteins.
Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines
Authors: Demuth Tim , Rennert Jessica L , Hoelzinger Dominique B , Reavie Linsey B , Nakada Mitsutoshi , Beaudry Christian , Nakada Satoko , Anderson Eric M , Henrichs Amanda N , McDonough Wendy S , Holz David , Joy Anna , Lin Richard , Pan Kuang H , Lih Chih J , Cohen Stan N , Berens Michael E
Published: January 2008

Background

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death.

To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis.

Results

Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA) revealed two discriminating patterns between migrating and stationary glioma cells: i) global down-regulation and ii) global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF). siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells.

Conclusion

Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected candidates were validated clinically at the transcriptional and translational levels as well as through functional assays thereby underscoring the fidelity of the discovery algorithm.
Mutational and transcriptional analyses of an avian pathogenic Escherichia coli ColV plasmid
Authors: Skyberg Jerod A , Johnson Timothy J , Nolan Lisa K
Published: January 2008

Background

Previously we described a 184-kb ColV plasmid, pAPEC-O2-ColV, that contributed to the ability of an E. coli to kill avian embryos, grow in human urine, and colonize the murine kidney. Here, the roles of several genes encoded by this plasmid in virulence were assessed using mutational and transcriptional analyses.

Methods

Genes chosen for deletion were iss, tsh, iutA, iroN, sitA, and cvaB. In addition, a 35-kb region of the plasmid, containing iss, tsh, and the ColV and iro operons, along with a 15-kb region containing both the aerobactin and sit operons, were deleted. Mutants were compared to the wild-type (APEC O2) for lethality to chick embryos and growth in human urine. Expression of the targeted genes was also assessed under these same conditions using RT-PCR

Results

No significant differences between the mutants and the wild-type in these phenotypic traits were detected. However, genes encoding known or predicted iron transport systems were up-regulated during growth in human urine, as compared to growth in LB broth, while iss, hlyF, and iroN were strongly up-regulated in chick embryos.

Conclusion

While no difference was observed between the mutant strains and their wild-type parent in the phenotypic traits assayed, we reasoned that some compensatory virulence mechanism, insensitivity of the virulence assays, or other factor could have obscured changes in the virulence of the mutants. Indeed we found several of these genes to be up-regulated in human urine and/or in the chick embryo, suggesting that certain genes linked to ColV plasmids are involved in the establishment of avian extraintestinal infection.
Using magnetic resonance microscopy to study the growth dynamics of a glioma spheroid in collagen I: A case study
Authors: Huang Shuning , Vader David , Wang Zhihui , Stemmer-Rachamimov Anat , Weitz David A , Dai Guangping , Rosen Bruce R , Deisboeck Thomas S
Published: January 2008

Background

Highly malignant gliomas are characterized by rapid growth, extensive local tissue infiltration and the resulting overall dismal clinical outcome. Gaining any additional insights into the complex interaction between this aggressive brain tumor and its microenvironment is therefore critical. Currently, the standard imaging modalities to investigate the crucial interface between tumor growth and invasion in vitro are light and confocal laser scanning microscopy. While immensely useful in cell culture, integrating these modalities with this cancer's clinical imaging method of choice, i.e. MRI, is a non-trivial endeavour. However, this integration is necessary, should advanced computational modeling be able to utilize these in vitro data to eventually predict growth behaviour in vivo. We therefore argue that employing the same imaging modality for both the experimental setting and the clinical situation it represents should have significant value from a data integration perspective. In this case study, we have investigated the feasibility of using a specific form of MRI, i.e. magnetic resonance microscopy or MRM, to study the expansion dynamics of a multicellular tumor spheroid in a collagen type I gel.

Methods

An U87mEGFR human giloblastoma multicellular spheroid (MTS) containing approximately 4·103 cells was generated and pipetted into a collagen I gel. The sample was then imaged using a T2-weighted 3D spoiled gradient echo pulse sequence on a 14T MRI scanner over a period of 12 hours with a temporal resolution of 3 hours at room temperature. Standard histopathology was performed on the MRM sample, as well as on control samples.

Results

We were able to acquire three-dimensional MR images with a spatial resolution of 24 × 24 × 24 μm3. Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period. The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control.

Conclusion

In this study, we demonstrate that a specific form of MRI, i.e. magnetic resonance microscopy or MRM, can be used to study the dynamic growth of a multicellular tumor spheroid (MTS) with a single cell scale spatial resolution that approaches the level of light microscopy. We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.
The orthopaedic trauma literature: an evaluation of statistically significant findings in orthopaedic trauma randomized trials
Authors: Sung Jinsil , Siegel Judith , Tornetta Paul , Bhandari Mohit
Published: January 2008

Background

Evidence-based medicine posits that health care research is founded upon clinically important differences in patient centered outcomes. Statistically significant differences between two treatments may not necessarily reflect a clinically important difference. We aimed to quantify the sample sizes and magnitude of treatment effects in a review of orthopaedic randomized trials with statistically significant findings.

Methods

We conducted a comprehensive search (PubMed, Cochrane) for all randomized controlled trials between 1/1/95 to 12/31/04. Eligible studies include those that focused upon orthopaedic trauma. Baseline characteristics and treatment effects were abstracted by two reviewers. Briefly, for continuous outcome measures (ie functional scores), we calculated effect sizes (mean difference/standard deviation). Dichotomous variables (ie infection, nonunion) were summarized as absolute risk differences and relative risk reductions (RRR). Effect sizes >0.80 and RRRs>50% were defined as large effects.

Using regression analysis we examined the association between the total number of outcome events and treatment effect (dichotomous outcomes).

Results

Our search yielded 433 randomized controlled trials (RCTs), of which 76 RCTs with statistically significant findings on 184 outcomes (122 continuous/62 dichotomous outcomes) met study eligibility criteria. The mean effect size across studies with continuous outcome variables was 1.7 (95% confidence interval: 1.43–1.97). For dichotomous outcomes, the mean risk difference was 30% (95%confidence interval:24%–36%) and the mean relative risk reduction was 61% (95% confidence interval: 55%–66%; range: 0%–97%). Fewer numbers of total outcome events in studies was strongly correlated with increasing magnitude of the treatment effect (Pearson's R = -0.70, p < 0.01). When adjusted for sample size, the number of outcome events revealed an independent association with the size of the treatment effect (Odds ratio = 50, 95% confidence interval: 3.0–1000, p = 0.006).

Conclusion

Our review suggests that statistically significant results in orthopaedic trials have the following implications-1) On average large risk reductions are reported 2) Large treatment effects (>50% relative risk reduction) are correlated with few number of total outcome events. Readers should interpret the results of such small trials with these issues in mind.
Clinical training: a simulation program for phlebotomy
Authors: Taniguchi Jun-ichi , Matsui Kunihiko , Araki Toshitaka , Kikawa Kazuhiko
Published: January 2008

Background

Basic clinical skills training in the Japanese medical education system has traditionally incorporated on-the-job training with patients. Recently, the complementary use of simulation techniques as part of this training has gained popularity. It is not known, however, whether the participants view this new type of education program favorably; nor is the impact of this program known. In this study we developed a new simulation-based training program in phlebotomy for new medical residents and assessed their satisfaction with the program

Methods

The education program comprised two main components: simulator exercise sessions and the actual drawing of blood from other trainees. At the end of the session, we surveyed participant sentiment regarding the program.

Results

There were 43 participants in total. In general, they were highly satisfied with the education program, with all survey questions receiving scores of 3 or more on a scale of 1–5 (mean range: 4.3 – 4.8), with 5 indicating the highest level of satisfaction. Additionally, their participation as a 'patient' for their co-trainees was undertaken willingly and was deemed to be a valuable experience.

Conclusion

We developed and tested an education program using a simulator for blood collection. We demonstrated a high satisfaction level among the participants for this unique educational program and expect that it will improve medical training, patient safety, and quality of care. The development and dissemination of similar educational programs involving simulation for other basic clinical skills will be undertaken in the future.
Intra-articular hyaluronic acid for treatment of osteoarthritis: a nationwide study among the older population of Taiwan
Authors: Lai Hsiu-Yun , Chen Yu-Chun , Chen Tzeng-Ji , Chou Li-Fang , Chen Liang-Kung , Hwang Shinn-Jang
Published: January 2008

Background

Although intra-articular treatment with hyaluronic acid (HA) for symptomatic osteoarthritis has become widely accepted in recent decades, the pattern of its use has seldom been reported. We have explored the epidemiology of intra-articular HA treatment in Taiwan by using the rich data source from nationwide insurance claims.

Methods

Taiwan's National Health Insurance (NHI), which covers 97% of inhabitants, offers extensive hospitalisation and ambulatory care. We identified the beneficiaries aged 60 years and older who received intra-articular HA within the NHI during 2004. The number of visits in which HA was administered were analysed by patient's age and gender and by the physician's specialty and practice site.

Results

Among the 73,410,777 ambulatory visits by 2,909,219 beneficiaries aged 60 years and older in 2004, 35,782 (1.2%) patients received intra-articular HA treatment in 205,012 (0.3%) visits. The highest prevalence of HA use was in the 70–79 year age group in both sexes. Women received intra-articular HA treatment more frequently than men in all age groups, especially in the 60–69 and 70–79 year groups (1.6% vs. 0.5%, 2.2% vs. 1.0%, respectively). Most intra-articular HA procedures were performed by orthopaedic surgeons (75.1%) and physical medicine and rehabilitation physicians (15.2%), and at metropolitan hospitals (34.5%) and local community hospitals (38.2%).

Conclusion

One out of 100 older patients in Taiwan received intra-articular HA treatment for osteoarthritis of the knee during the course of the year. There were age-gender differences in use of HA treatment. The completion rate of this treatment in our study was high, and thus intra-articular HA might be a good alternative for patients for whom conventional treatment fails. Further research is needed to examine the age-gender differences in use of intra-articular HA in Taiwan.
In vitro atovaquone/proguanil susceptibility and characterization of the cytochrome b gene of Plasmodium falciparum from different endemic regions of Thailand
Authors: Khositnithikul Rommanee , Tan-ariya Peerapan , Mungthin Mathirut
Published: January 2008

Background

The emergence of Plasmodium falciparum resistant to most currently used antimalarial drugs is the major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Although artemisinin-based combination therapy has been recommended for the treatment of multidrug-resistant falciparum malaria, these combinations are not available for some people, such as travelers from North America. A fixed-dose combination of atovaquone and proguanil (Malarone) has been proved to be effective for the treatment and prophylaxis of malaria which is already approved by countries in North America and Europe. Determination of the phenotypes and genotypes related to atovaquone/proguanil response in Thai isolates of P. falciparum will be useful for rationale drug use. The main purpose of this study was to explore the in vitro atovaquone/proguanil susceptibility of recently adapted Thai isolates of P. falciparum. Genotypic characterization of the cytb gene of these isolates was also determined since it has been reported that point mutations, particularly codon 268 in the cytochrome b gene (cytb) have been linked to atovaquone/proguanil treatment failure.

Methods

Eighty three P. falciparum isolates collected during 1998 to 2005 from four different multidrug resistance areas of Thailand were determined for the in vitro atovaquone/proguanil susceptibilities using radioisotopic assay. Mutations in the cytb gene were determined by PCR-RFLP and sequence analysis.

Results

The mean atovaquone and proguanil IC50 was 3.4 nM and 36.5 μM, respectively. All 83 Thai isolates were atovaquone sensitive. None of the 83 isolates contained the mutations at codon 268 of the cytb gene. DNA sequencing of the cytb gene of 20 parasite isolates showed no other mutations.

Conclusion

In agreement with a recent efficacy study of atovaquone/proguanil, the present information indicates that atovaquone/proguanil can be one of the drugs of choice for the treatment and prophylaxis of multidrug-resistant falciparum malaria in Thailand.
To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended
Authors: Colombo Ottavia , Villani Simona , Pinelli Giovanna , Trentani Claudia , Baldi Maurizia , Tomarchio Orazio , Tagliabue Anna
Published: January 2008

Background

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m2. The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.

Methods

We compared treatment need based on BMI classification with four adiposity-based criteria: percentage body fat (%BF), considered both alone and in relation to metabolic syndrome risk (MS), waist circumference (WC), as an index of abdominal fat, and Body Fat Mass Index (BFMI, calculated as fat mass in kg divided by height in m2) in 63 volunteers (23 men and 40 women, aged 20 – 65 years).

Results

According to the classification based on BMI, 6.3% of subjects were underweight, 52.4% were normal weight, 30.2% were overweight, and 11.1% were obese. Agreement between the BMI categories and the other classification criteria categories varied; the most notable discrepancy emerged in the underweight and overweight categories. BMI compared to almost all of the other adiposity-based criteria, identified a lower percentage of subjects for whom treatment would be recommended. In particular, the proportion of subjects for whom clinicians would strongly recommend weight loss on the basis of their BMI (11.1%) was significantly lower than those identified according to WC (25.4%, p = 0.004), %BF (28.6%, p = 0.003), and MS (33.9%, p = 0.002).

Conclusion

The use of the BMI alone, as opposed to an assessment based on body composition, to identify individuals needing lifestyle intervention may lead to unfortunate misclassifications. Population-specific data on the relationships between body composition, morbidity, and mortality are needed to improve the diagnosis and treatment of at-risk individuals.
Automated production of recombinant human proteins as resource for proteome research
Authors: Kohl Thorsten , Schmidt Christian , Wiemann Stefan , Poustka Annemarie , Korf Ulrike
Published: January 2008

Background

An arbitrary set of 96 human proteins was selected and tested to set-up a fully automated protein production strategy, covering all steps from DNA preparation to protein purification and analysis. The target proteins are encoded by functionally uncharacterized open reading frames (ORF) identified by the German cDNA consortium. Fusion proteins were produced inE. coliwith four different fusion tags and tested in five different purification strategies depending on the respective fusion tag. The automated strategy relies on standard liquid handling and clone picking equipment.

Results

A robust automated strategy for the production of recombinant human proteins inE. coliwas established based on a set of four different protein expression vectors resulting in NusA/His, MBP/His, GST and His-tagged proteins. The yield of soluble fusion protein was correlated with the induction temperature and the respective fusion tag. NusA/His and MBP/His fusion proteins are best expressed at low temperature (25°C), whereas the yield of soluble GST fusion proteins was higher when protein expression was induced at elevated temperature. In contrast, the induction of soluble His-tagged fusion proteins was independent of the temperature. Amylose was not found useful for affinity-purification of MBP/His fusion proteins in a high-throughput setting, and metal chelating chromatography is recommended instead.

Conclusion

Soluble fusion proteins can be produced inE. coliin sufficient qualities and μg/ml culture quantities for downstream applications like microarray-based assays, and studies on protein-protein interactions employing a fully automated protein expression and purification strategy. Future applications might include the optimization of experimental conditions for the large-scale production of soluble recombinant proteins from libraries of open reading frames.
The histone chaperone protein Nucleosome Assembly Protein-1 (hNAP-1) binds HIV-1 Tat and promotes viral transcription
Authors: Vardabasso Chiara , Manganaro Lara , Lusic Marina , Marcello Alessandro , Giacca Mauro
Published: January 2008

Background

Despite the large amount of data available on the molecular mechanisms that regulate HIV-1 transcription, crucial information is still lacking about the interplay between chromatin conformation and the events that regulate initiation and elongation of viral transcription. During transcriptional activation, histone acetyltransferases and ATP-dependent chromatin remodeling complexes cooperate with histone chaperones in altering chromatin structure. In particular, human Nucleosome Assembly Protein-1 (hNAP-1) is known to act as a histone chaperone that shuttles histones H2A/H2B into the nucleus, assembles nucleosomes and promotes chromatin fluidity, thereby affecting transcription of several cellular genes.

Results

Using a proteomic screening, we identified hNAP-1 as a novel cellular protein interacting with HIV-1 Tat. We observed that Tat specifically binds hNAP1, but not other members of the same family of factors. Binding between the two proteins required the integrity of the basic domain of Tat and of two separable domains of hNAP-1 (aa 162–290 and 290–391). Overexpression of hNAP-1 significantly enhanced Tat-mediated activation of the LTR. Conversely, silencing of the protein decreased viral promoter activity. To explore the effects of hNAP-1 on viral infection, a reporter HIV-1 virus was used to infect cells in which hNAP-1 had been either overexpressed or knocked-down. Consistent with the gene expression results, these two treatments were found to increase and inhibit viral infection, respectively. Finally, we also observed that the overexpression of p300, a known co-activator of both Tat and hNAP-1, enhanced hNAP-1-mediated transcriptional activation as well as its interaction with Tat.

Conclusion

Our study reveals that HIV-1 Tat binds the histone chaperone hNAP-1 both in vitro and in vivo and shows that this interaction participates in the regulation of Tat-mediated activation of viral gene expression.
The tryptophan pathway genes of the Sargasso Sea metagenome: new operon structures and the prevalence of non-operon organization
Authors: Kagan Juliana , Sharon Itai , Beja Oded , Kuhn Jonathan C
Published: January 2008

Background

The enormous database of microbial DNA generated from the Sargasso Sea metagenome provides a unique opportunity to locate genes participating in different biosynthetic pathways and to attempt to understand the relationship and evolution of those genes. In this article, an analysis of the Sargasso Sea metagenome is made with respect to the seven genes of the tryptophan pathway.

Results

At least 5% of all the genes that are related to amino acid biosynthesis are tryptophan (trp) genes. Many contigs and scaffolds contain whole or split operons that are similar to previously analyzed trp gene organizations. Only two scaffolds discovered in this analysis possess a different operon organization of tryptophan pathway genes than those previously known. Many marine organisms lack an operon-type organization of these genes or have mini-operons containing only two trp genes. In addition, the trpB genes from this search reveal that the dichotomous division between trpB_1 and trpB_2 also occurs in organisms from the Sargasso Sea. One cluster was found to contain trpB sequences that were closely related to each other but distinct from most known trpB sequences.

Conclusion

The data show that trp genes are widely dispersed within this metagenome. The novel organization of these genes and an unusual group of trpB_1 sequences that were found among some of these Sargasso Sea bacteria indicate that there is much to be discovered about both the reason for certain gene orders and the regulation of tryptophan biosynthesis in marine bacteria.
Ethical, Scientific, and Regulatory Perspectives Regarding the Use of Placebos in Cancer Clinical Trials
Authors: Daugherty Christopher K. , Ratain Mark J. , Emanuel Ezekiel J. , Farrell Ann T. , Schilsky Richard L.
Published: January 2008

Purpose

To examine the ethical, scientific, and regulatory issues in the design and conduct of placebo-controlled cancer clinical trials.

Methods

Several content experts contributed to this article.

Results

Specific criteria can be applied to determine the appropriate use of placebos in oncology drug development. Placebo controls may be justified to prove efficacy of a new treatment in diseases with high placebo response rates; in conditions that wax and wane in severity, have spontaneous remissions, or have an uncertain and unpredictable course; when existing therapies are minimally effective or have serious adverse effects; or in the absence of effective therapy. Use of placebos may also be justified to assure blinding of physicians and patients regarding treatment assignment so as to minimize bias in assessment of study end points. If a trial meets these methodologic criteria, it must then fulfill additional criteria to be considered ethical. These criteria include full disclosure to patients and an assurance that participants randomly assigned to placebo are not substantially more likely than those in active treatment group(s) to die; suffer irreversible morbidity, disability, or other substantial harms; suffer reversible but serious harm; or suffer severe discomfort.

Conclusion

We conclude that placebo-controlled oncology trials are scientifically feasible, ethically justifiable, and may be necessary or desirable to meet regulatory standards for drug approval. Using cross-over or randomized withdrawal trial designs, requiring inclusion of state-of-the-art palliative care, and developing valid and acceptable surrogates for survival are critical strategies to address some of the ethical dilemmas associated with placebo-controlled trials.
Darbepoetin Alfa for the Treatment of Anemia in Patients With Active Cancer Not Receiving Chemotherapy or Radiotherapy: Results of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Smith Robert E. , Aapro Matti S. , Ludwig Heinz , Pintér Tamás , Šmakal Martin , Ciuleanu Tudor E. , Chen Li , Lillie Tom , Glaspy John A.
Published: January 2008

Purpose

The efficacy and safety of darbepoetin alfa (DA) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated.

Patients and Methods

Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III, multicenter, randomized, placebo-controlled study and administered placebo or DA 6.75 μg/kg every 4 weeks (Q4W) for up to 16 weeks with a 2-year follow-up for survival. Patients who completed 16 weeks of treatment could receive the same treatment as randomized Q4W for an additional 16 weeks. The primary end point was all occurrences of transfusions from weeks 5 through 17; safety end points included incidence of adverse events and survival.

Results

The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo. DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period. Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo (P = .022). This effect varied by baseline covariates including, sex, tumor type, and geographic region; statistical significance diminished (P = .12) when the analysis was adjusted for baseline imbalances or known prognostic factors.

Conclusion

DA was not associated with a statistically significant reduction in transfusions. Shorter survival was observed in the DA arm; thus, this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer.
The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme
Authors: Umlauf David , Fraser Peter , Nagano Takashi
Published: January 2008

Transcriptome studies have uncovered a plethora of non-coding RNAs (ncRNA) in mammals. Most originate within intergenic regions of the genome and recent evidence indicates that some are involved in many different pathways that ultimately act on genome architecture and gene expression. In this review, we discuss the role of well-characterized long ncRNAs in gene regulation pointing to their similarities, but also their differences. We will attempt to highlight a paradoxical situation in which transcription is needed to repress entire chromosomal domains possibly through the action of ncRNAs that create nuclear environments refractory to transcription.
Role of histone modifications in defining chromatin structure and function
Authors: Gelato Kathy A. , Fischle Wolfgang
Published: January 2008

Chromosomes in eukaryotic cell nuclei are not uniformly organized, but rather contain distinct chromatin elements, with each state having a defined biochemical structure and biological function. These are recognizable by their distinct architectures and molecular components, which can change in response to cellular stimuli or metabolic requirements. Chromatin elements are characterized by the fundamental histone and DNA components, as well as other associated non-histone proteins and factors. Post-translational modifications of histone proteins in particular often correlate with a specific chromatin structure and function. Patterns of histone modifications are implicated as having a role in directing the level of chromatin compaction, as well as playing roles in multiple functional pathways directing the readout of distinct regions of the genome. We review the properties of various chromatin elements and the apparent links of histone modifications with chromatin organization and functional output.
Measuring “Fast” Shear Strengths Along Slickensided Surfaces in the Bromhead Ring Shear
Authors: Meehan Christopher L. , Brandon Thomas L. , Michael Duncan J.
Published: January 2008

Fast and slow ring shear tests were performed in the Bromhead ring shear device to examine the effect of the displacement rate on the shear strength measured along slickensided discontinuities in Rancho Solano Fat Clay. For each test, initial drained shearing was performed at a displacement rate of 0.018 mm/min, fast shearing was performed at a rate of 44.5 mm/min, and drained shearing was recommenced at a displacement rate of 0.018 mm/min. Significant variations in measured post-peak shear strengths were observed, and problems with the pore pressure response in the soil surrounding the slickensided plane are discussed. As a result of these problems, it was concluded that fast Bromhead ring shear tests may not be suitable for evaluating the effects of fast shearing on the strengths of slickensided surfaces.