bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence Rate and Factors Related to Post-Bronchoalveolar Lavage Fever in Children
Authors: Mohallem Fonseca M.T. , Camargos P.A.M. , Abou Taam R. , Le Bourgeois M. , Scheinmann P. , de Blic J.
Published: August 2007

Background: Post-bronchoscopy and bronchoalveolar lavage (BAL) fever in children has been described by several authors. Objectives: This study aimed at assessing the occurrence of fever after these examinations and associated risk factors. Methods: The study was performed in the Bronchoscopy Unit of Hôpital Necker-Enfants Malades, Paris, France, from June 2004 to July 2005. 148 children who underwent fiberoptic bronchoscopy and BAL, and remained in the Unit for 24 h, were included. Results: 37.8% of the patients presented post-BAL fever. In the multivariate analysis of the selected factors (age, immunodeficiency, general or local anesthesia, mucosal biopsy, inflammation and suppuration at the moment of the examination, abnormal bronchoalveolar fluid cellularity and infection), only age <2 years and presence of infection remained associated with fever. Conclusions: The occurrence of fever is a frequent event in children who underwent BAL. In order to reduce post-BAL fever, antibiotic strategies should be devised based on prospective studies assessing identification of predictive air-way infection criteria and/or rapid bacteriological result analysis.
Multimethod Measurement of High-Risk Drinking Locations
Authors: Kelley-Baker Tara , Voas Robert B. , Johnson Mark B. , Furr-Holden C. Debra M. , Compton Christine
Published: August 2007

Portal survey techniques involve multimodal assessments (e.g., self-report, biologic, and observational) in high-risk drinking and drug-use settings. Our investigation expanded the portal survey methodology to include follow-up assessments of emerging adult women recruited at the border as they cross to and from Mexico south of San Diego, California. The feasibility of the follow-up procedure was established, and the limitations of the technique clarified. Follow-up participants and nonparticipants did not differ by age or reported victimization. Data indicated that 8% of women experience negative events on their return to the United States after a night of binge drinking. These experiences could only be captured in a follow-up survey, as they happened after participants left the border area.
The Decision to Conduct a Head-to-Head Comparative Trial: A Game-Theoretic Analysis
Authors: Mansley Edward C. , Elbasha Elamin H. , Teutsch Steven M. , Berger Marc L.
Published: August 2007

Recent Medicare legislation calls on the Agency for Healthcare Research and Quality to conduct research related to the comparative effectiveness of health care items and services, including prescription drugs. This reinforces earlier calls for head-to-head comparative trials of clinically relevant treatment alternatives. Using a game-theoretic model, the authors explore the decision of pharmaceutical companies to conduct such trials. The model suggests that an important factor affecting this decision is the potential loss in market share and profits following a result of inferiority or comparability. This hidden cost is higher for the market leader than the market follower, making it less likely that the leader will choose to conduct a trial. The model also suggests that in a full-information environment, it will never be the case that both firms choose to conduct such a trial. Furthermore, if market shares and the probability of proving superiority are similar for both firms, it is quite possible that neither firm will choose to conduct a trial. Finally, the results indicate that incentives that offset the direct cost of a trial can prevent a no-trial equilibrium, even when both firms face the possibility of an inferior outcome.
The Long-term Consequence of Anterior Cruciate Ligament and Meniscus Injuries
Authors: Lohmander L. Stefan , Englund P. Martin , Dahl Ludvig L. , Roos Ewa M.
Published: August 2007

The objectives of this study are to review the long-term consequences of injuries to the anterior cruciate ligament and menisci, the pathogenic mechanisms, and the causes of the considerable variability in outcome. Injuries of the anterior cruciate ligament and menisci are common in both athletes and the general population. At 10 to 20 years after the diagnosis, on average, 50% of those with a diagnosed anterior cruciate ligament or meniscus tear have osteoarthritis with associated pain and functional impairment: the young patient with an old knee. These individuals make up a substantial proportion of the overall osteoarthritis population. There is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against osteoarthritis development. A consistent finding in a review of the literature is the often poor reporting of critical study variables, precluding data pooling or a meta-analysis. Osteoarthritis development in the injured joints is caused by intra-articular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading. Variation in outcome is reinforced by additional variables associated with the individual such as age, sex, genetics, obesity, muscle strength, activity, and reinjury. A better understanding of these variables may improve future prevention and treatment strategies. In evaluating medical treatment, we now expect large randomized clinical trials complemented by postmarketing monitoring. We should strive toward a comparable level of quality of evidence in surgical treatment of knee injuries. In instances in which a randomized clinical trial is not feasible, natural history and other observational cohort studies need to be as carefully designed and reported as the classic randomized clinical trial, to yield useful information.
Neuromuscular and Lower Limb Biomechanical Differences Exist between Male and Female Elite Adolescent Soccer Players during an Unanticipated Run and Crosscut Maneuver
Authors: Landry Scott C. , McKean Kelly A. , Hubley-Kozey Cheryl L. , Stanish William D. , Deluzio Kevin J.
Published: August 2007

Background

Noncontact anterior cruciate ligament injuries often occur during sports such as soccer and basketball in which cutting or landing maneuvers are frequently performed. These injuries are more common in female athletes, and identifying biomechanical or neuromuscular risk factors related to gender may help with the development of preventive training programs aimed at reducing anterior cruciate ligament injury.

Hypothesis

Lower limb biomechanical and/or neuromuscular differences between male and female soccer players will be identified during unanticipated running and cutting maneuvers.

Study Design

Descriptive laboratory study.

Methods

A complete 3-dimensional kinematic, kinetic, and electromyographic analysis of the lower limb for an unanticipated straight-run and crosscut maneuver was performed on 42 (male, 21; female, 21) elite adolescent soccer players.

Results

For both maneuvers, female players had greater lateral gastrocnemius activity, normalized to maximal voluntary isometric contractions, and demonstrated a mediolateral gastrocnemii imbalance that was not present in male players. Rectus femoris activity for both maneuvers and vastus medialis and lateralis activity for the straight run only were also greater in female than in male athletes. Other notable differences captured for the maneuvers included female players having reduced hamstring activity, a reduced hip flexion moment, a reduced hip flexion angle, and an increased ankle eversion angle throughout stance compared with male players.

Conclusion

This is one of the first studies to identify gastrocnemii differences between genders as a possible anterior cruciate ligament injury risk factor. Additional biomechanical and neuromuscular differences were also identified as potential risk factors.

Clinical Relevance

These findings provide insight into the noncontact anterior cruciate ligament injury gender bias and may help improve preventive training programs.
Spinal Muscular Atrophy: Classification, Diagnosis, Management, Pathogenesis, and Future Research Directions
Authors: Kostova Felina V. , Williams Virginia C. , Heemskerk Jill , Iannaccone Susan , DiDonato Christine , Swoboda Kathryn , Maria Bernard L.
Published: August 2007

Spinal muscular atrophy is an autosomal recessive neurodegenerative disorder that affects the motor neurons responsible for movement of the proximal muscles of the trunk and body. To date, the disease can be classified into 3 main categories based on severity and age of onset. During the October 18th symposium held in Pittsburgh, Pennsylvania, researchers met to (1) describe current diagnostic strategies, (2) discuss recent thoughts on pathogenesis, (3) review current therapies and clinical trials, and (4) define future research directions. In her opening remarks, Dr Story Landis, director of the National Institute of Neurological Disorders and Stroke, emphasized the degree to which the Neurobiology of Disease in Children conference series has broadened awareness of the many rare diseases affecting children, not only through the advancement of research but also by educating practitioners about diagnostic strategies. Dr Landis also discussed the role this conference may play in fostering research that seeks to develop a single mechanism of therapy for spinal muscular atrophy. She also discussed the current funding situation at the National Institutes of Health and addressed the crucial function of volunteer research organizations that sponsor research in further improving management of this condition. This article summarizes the presentations and includes the verbatim edited transcript of question-and-answer sessions.
Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling
Authors: Shanmugarajan Srinivasan , Swoboda Kathryn J. , Iannaccone Susan T. , Ries William L. , Maria Bernard L. , Reddy Sakamuri V.
Published: August 2007

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene ( SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity.
Perspectives on Clinical Trials in Spinal Muscular Atrophy
Authors: Swoboda Kathryn J. , Kissel John T. , Crawford Thomas O. , Bromberg Mark B. , Acsadi Gyula , D'Anjou Guy , Krosschell Kristin J. , Reyna Sandra P. , Schroth Mary K. , Scott Charles B. , Simard Louise R.
Published: August 2007

Spinal muscular atrophy is one of the most heterogeneous of the single-gene neuromuscular disorders. The broad spectrum of severity, with onset from the prenatal period to adulthood, presents unique challenges in the design and implementation of clinical trials. The clinical classification of subjects into severe (type 1), intermediate (type 2), and mild (type 3) subtypes has proved useful both in enhancing communication among clinicians internationally and in forging the collaborative development of outcome measures for clinical trials. Ideally, clinical trial design in spinal muscular atrophy must take into account the spinal muscular atrophy type, patient age, severity-of-affection status, nature of the therapeutic approach, timing of the proposed intervention relative to disease progression, and relative homogeneity of the cohort to be studied. Following is an overview of the challenges and opportunities, current and future therapeutic strategies, and progress to date in clinical trials in spinal muscular atrophy.
Fishing for a Mechanism: Using Zebrafish to Understand Spinal Muscular Atrophy
Authors: Beattie Christine E. , Carrel Tessa L. , McWhorter Michelle L.
Published: August 2007

Motoneuron diseases cause paralysis and death due to loss of motoneurons that innervate skeletal muscle. Spinal muscular atrophy is a human motoneuron disease that is genetically linked to the survival motor neuron gene ( SMN). Although SMN was identified more than a decade ago, it remains unclear how decreased levels of the SMN protein cause spinal muscular atrophy. The use of animal models, however, offers a crucial tool in determining the function of SMN in this disease. In this review, we discuss our efforts to develop a zebrafish model of spinal muscular atrophy.
Spinal Muscular Atrophy Genetic Counseling Access and Genetic Knowledge: Parents' Perspectives
Authors: Meldrum Candice , Scott Charles , Swoboda Kathryn J.
Published: August 2007

Spinal muscular atrophy is characterized by degeneration of α motor neurons in the anterior horns of the spinal cord, which leads to progressive symmetrical muscle weakness and atrophy. Spinal muscular atrophy is the leading fatal autosomal recessive disorder in infancy, and genetic counseling is an essential component of the care of families of these patients. However, little guidance is available in the published literature regarding the process and benefit of genetic counseling for families. Accordingly, the authors designed a questionnaire to assess parents' knowledge of the disease, gauge their access to genetic counseling, and determine how parents use information gained from counseling to guide choices for future pregnancies. The questionnaire specifically targeted when genetic counseling was received, from whom, parental knowledge regarding spinal muscular atrophy genetics, parental choices regarding spinal muscular atrophy and their child, frequency of prenatal testing, perceived relevance of newborn screening, and opinions regarding the disease. Most families clearly received some type of genetic counseling. Yet how and from whom they received the information varied greatly, as did their genetic knowledge of spinal muscular atrophy. The highest percentage of families received counseling from neurologists, who may not be appropriately prepared to provide formal genetic counseling. Many respondents reported having a negative experience with genetic counseling, possibly because it occurred at the time of diagnosis or shortly afterward, a period of great emotional turmoil. These data suggest that a consistent approach for facilitating how and when genetic counseling is received is greatly needed.
Molecular Mechanisms of Spinal Muscular Atrophy
Authors: Sumner Charlotte J.
Published: August 2007

Significant strides have been made during the past decade in the understanding of the molecular mechanisms that lead to the autosomal recessive motor neuron disease spinal muscular atrophy. Genetic studies revealed that spinal muscular atrophy is caused by mutation of the telomeric copy of the survival motor neuron gene ( SMN1), with all patients retaining at least one copy of the centromeric form of the gene, SMN2. SMN2 produces reduced amounts of full-length SMN messenger ribonucleic acid because of alterative splicing of SMN2 -derived transcripts, a process that is governed by specific cisand trans-acting factors. The resulting insufficient expression level of full-length SMN protein likely causes the disease manifestations of spinal muscular atrophy; however, the mechanism for the selective vulnerability of the motor unit to deficiency of this ubiquitously expressed protein remains unknown. It also remains unclear specifically when and where in the motor unit SMN is required. Despite the remaining questions, progress has been made in developing therapeutic strategies targeted to specific points along the pathogenetic pathway of spinal muscular atrophy. Histone deacetylase inhibitors will be discussed as an example.
Consensus Statement for Standard of Care in Spinal Muscular Atrophy
Authors: Wang Ching H. , Finkel Richard S. , Bertini Enrico S. , Schroth Mary , Simonds Anita , Wong Brenda , Aloysius Annie , Morrison Leslie , Main Marion , Crawford Thomas O. , Trela Anthony ,   Participants of the International Conference on SMA Standard of Care
Published: August 2007

Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal muscular atrophy and advances in medical technology have not been matched by similar developments in the care for spinal muscular atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal muscular atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal muscular atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal muscular atrophy is urgently needed to help with the multidisciplinary care of these patients.
To Rank or To Be Ranked: The Impact of Global Rankings in Higher Education
Authors: Marginson Simon , van der Wende Marijk
Published: August 2007

Global university rankings have cemented the notion of a world university market arranged in a single “league table” for comparative purposes and have given a powerful impetus to intranational and international competitive pressures in the sector. Both the research rankings by Shanghai Jiao Tong University and the composite rankings by the Times Higher Education Supplement have been widely publicised and already appear to have generated incentives in favour of greater system stratification and the concentration of elite researchers. However, global comparisons are possible only in relation to one model of institution, that of the comprehensive research intensive university, and for the most part are tailored to science-strong and English-speaking universities. Neither the Shanghai nor the Times rankings provide guidance on the quality of teaching. It is important to secure “clean” rankings, transparent, free of self-interest, and methodologically coherent, that create incentives to broad-based improvement.
The Global Campus: Challenges and Opportunities for Higher Education in North America
Authors: Brustein William I.
Published: August 2007

Confronted with a world that is strikingly different from what it was just a decade ago, the United States faces rapidly shifting economic, political, and national security realities and challenges. To respond to these changes it is essential that our institutions of higher education graduate globally competent students. This article addresses several major challenges confronting international educators within the United States including redesigning the curriculum, achieving faculty buy-in, financing study abroad, integrating our international students in the efforts to internationalize our campus, and rethinking how we teach foreign languages on our campuses.
The Internationalisation of Higher Education in South Africa: Progress and Challenges
Authors: Kishun Roshen
Published: August 2007

South Africa needs to reexamine responses to some basic questions if it is to develop a robust push that would enable the higher education sector to maximise the benefits of internationalisation in the context of the “knowledge society” and to serve local needs while being an integral part of the global community. In responding to these questions, this article posits the view that the history and future of the internationalisation of higher education in South Africa would make a useful contribution to ongoing debates on this important topic. The article probes the internationalisation of higher education in South Africa against the backdrop of the internationalisation globally. It also investigates future scenarios and topics ranging from the “Africanization versus internationalization” debate and policies on internationalisation to student mobility, trade in educational services, and how internationalisation is being used to ease skill shortages in developed countries.
Internationalisation of South African Higher Education in the Postapartheid Era
Authors: Rouhani Sepideh
Published: August 2007

During the past decade, there has been significant growth in the number of international students seeking access to South African higher education institutions. Concomitant with this growth has been a need for management of the internationalisation process at higher education institutions; however, this has not always been forthcoming. This article provides a comparative analysis of internationalisation in selected South African universities during the immediate postapartheid period since the 1990s. The process of establishing international offices or the lack thereof and the ongoing internationalisation of these institutions are analysed. In addition, the article considers other issues pertinent to the internationalisation of South African higher education institutions in the 21st century. The article draws on empirical research conducted by the author at various South African higher education institutions and is based on a mixed-method research design.
Distance to Public Test Sites and HIV Testing
Authors: Leibowitz Arleen A. , Taylor Stephanie L.
Published: August 2007

This article examines how proximity to the nearest publicly funded test site affects HIV testing. Using a sample of 5,361 Los Angeles County adults, multinomial logit models estimated simultaneously the likelihood of (1) obtaining an HIV test in the prior 2 years, and (2) testing in a private physician's office, a publicly funded medical clinic, or in a nonmedical setting, such as a bar or bathhouse. Low-income Los Angeles residents rely on publicly funded sites for HIV testing. When public sites are more distant, poor individuals are less likely to use them and less likely to get tested. Distance from public sites does not affect HIV testing among the nonpoor. To encourage HIV testing among the groups where HIV is growing fastest, public health agencies must keep the time and money costs of HIV testing low.
Evaluation of Community Action Against Asthma: A Community Health Worker Intervention to Improve Children's Asthma-Related Health by Reducing Household Environmental Triggers for Asthma
Authors: Parker Edith A. , Israel Barbara A. , Robins Thomas G. , Mentz Graciela , Xihong Lin  , Brakefield-Caldwell Wilma , Ramirez Erminia , Edgren Katherine K. , Salinas Maria , Lewis Toby C.
Published: August 2007

This article describes the evaluation of a community-based participatory research (CBPR) community health worker (CHW) intervention to improve children's asthma-related health by reducing household environmental triggers for asthma. After randomization to an intervention or control group, 298 households in Detroit, Michigan, with a child, aged 7 to 11, with persistent asthma symptoms participated. The intervention was effective in increasing some of the measures of lung function (daily nadir Forced Expiratory Volume at one second [ p = .03] and daily nadir Peak Flow [ p = .02]), reducing the frequency of two symptoms (“cough that won't go away,” “coughing with exercise”), reducing the proportion of children requiring unscheduled medical visits and reporting inadequate use of asthma controller medication, reducing caregiver report of depressive symptoms, reducing concentrations of dog allergen in the dust, and increasing some behaviors related to reducing indoor environmental triggers. The results suggest a CHW environmental intervention can improve children's asthma-related health, although the pathway for improvement is complex.
A State-Based Model of Prevention: Indiana's Example
Authors: Agley Jon , Gassman Ruth
Published: August 2007

Public health officials in the United States have battled alcohol, tobacco, and other drug (ATOD) use among adolescents for the past few decades, but only in 2002 did they begin to see a decline in rates of use. ATOD use and abuse are associated with numerous problems, including criminal behavior and increased adolescent morbidity and mortality rates. Researchers have sought to identify best-practice procedures for ATOD prevention; the state of Indiana has a strong ATOD prevention system in place that has the potential to serve as a model for other U.S. localities because of its best-practice approach to public health services. This article outlines the activities of the Indiana Prevention Resource Center to provide an example to strengthen public health professionals' ability to prevent ATOD use and abuse and to provide for a healthy adolescent population.
Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling
Authors: Wang Linlin , Schulz Thomas C. , Sherrer Eric S. , Dauphin Derek S. , Shin Soojung , Nelson Angelique M. , Ware Carol B. , Zhan Mei , Song Chao-Zhong , Chen Xiaoji , Brimble Sandii N. , McLean Amanda , Galeano Maria J. , Uhl Elizabeth W. , D'Amour Kevin A. , Chesnut Jonathan D. , Rao Mahendra S. , Blau C. Anthony , Robins Allan J.
Published: August 2007

Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs.
Inhibition of primordial germ cell proliferation by the medaka male determining gene Dmrt1bY
Authors: Herpin Amaury , Schindler Detlev , Kraiss Anita , Hornung Ute , Winkler Christoph , Schartl Manfred
Published: August 2007

Background

Dmrt1 is a highly conserved gene involved in the determination and early differentiation phase of the primordial gonad in vertebrates. In the fish medaka dmrt1bY, a functional duplicate of the autosomal dmrt1a gene on the Y-chromosome, has been shown to be the master regulator of male gonadal development, comparable to Sry in mammals. In males mRNA and protein expression was observed before morphological sex differentiation in the somatic cells surrounding primordial germ cells (PGCs) of the gonadal anlage and later on exclusively in Sertoli cells. This suggested a role for dmrt1bY during male gonad and germ cell development.

Results

We provide functional evidence that expression of dmrt1bY leads to negative regulation of PGC proliferation. Flow cytometric measurements revealed a G2 arrest of dmrt1bY expressing cells. Interestingly, also non-transfected cells displayed a significantly lower fraction of proliferating cells, pointing to a possible non-cell autonomous action of dmrt1bY. Injection of antisense morpholinos led to an increase of PGCs in genetically male embryos due to loss of proliferation inhibition.

Conclusion

In medaka, dmrt1bY mediates a mitotic arrest of PGCs in males prior to testes differentiation at the sex determination stage. This occurs possibly via a cross-talk of Sertoli cells and PGCs.
Non-coding antisense transcription detected by conventional and single-stranded cDNA microarray
Authors: Vallon-Christersson Johan , Staaf Johan , Kvist Anders , Medstrand Patrik , Borg Åke , Rovira Carlos
Published: August 2007

Background

Recent studies revealed that many mammalian protein-coding genes also transcribe their complementary strands. This phenomenon raises questions regarding the validity of data obtained from double-stranded cDNA microarrays since hybridization to both strands may occur. Here, we wanted to analyze experimentally the incidence of antisense transcription in human cells and to estimate their influence on protein coding expression patterns obtained by double-stranded microarrays. Therefore, we profiled transcription of sense and antisense independently by using strand-specific cDNA microarrays.

Results

Up to 88% of expressed protein coding loci displayed concurrent expression from the complementary strand. Antisense transcription is cell specific and showed a strong tendency to be positively correlated to the expression of the sense counterparts. Even if their expression is wide-spread, detected antisense signals seem to have a limited distorting effect on sense profiles obtained with double-stranded probes.

Conclusion

Antisense transcription in humans can be far more common than previously estimated. However, it has limited influence on expression profiles obtained with conventional cDNA probes. This can be explained by a biological phenomena and a bias of the technique: a) a co-ordinate sense and antisense expression variation and b) a bias for sense-hybridization to occur with more efficiency, presumably due to variable exonic overlap between antisense transcripts.
Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts
Authors: Seim Inge , Collet Chris , Herington Adrian C , Chopin Lisa K
Published: August 2007

Background

Ghrelin is a multifunctional peptide hormone expressed in a range of normal tissues and pathologies. It has been reported that the human ghrelin gene consists of five exons which span 5 kb of genomic DNA on chromosome 3 and includes a 20 bp non-coding first exon (20 bp exon 0). The availability of bioinformatic tools enabling comparative analysis and the finalisation of the human genome prompted us to re-examine the genomic structure of the ghrelin locus.

Results

We have demonstrated the presence of an additional novel exon (exon -1) and 5' extensions to exon 0 and 1 using comparative in silico analysis and have demonstrated their existence experimentally using RT-PCR and 5' RACE. A revised exon-intron structure demonstrates that the human ghrelin gene spans 7.2 kb and consists of six rather than five exons. Several ghrelin gene-derived splice forms were detected in a range of human tissues and cell lines. We have demonstrated ghrelin gene-derived mRNA transcripts that do not code for ghrelin, but instead may encode the C-terminal region of full-length preproghrelin (C-ghrelin, which contains the coding region for obestatin) and a transcript encoding obestatin-only. Splice variants that differed in their 5' untranslated regions were also found, suggesting a role of these regions in the post-transcriptional regulation of preproghrelin translation. Finally, several natural antisense transcripts, termed ghrelinOS (ghrelin opposite strand) transcripts, were demonstrated via orientation-specific RT-PCR, 5' RACE and in silico analysis of ESTs and cloned amplicons.

Conclusion

The sense and antisense alternative transcripts demonstrated in this study may function as non-coding regulatory RNA, or code for novel protein isoforms. This is the first demonstration of putative obestatin and C-ghrelin specific transcripts and these findings suggest that these ghrelin gene-derived peptides may also be produced independently of preproghrelin. This study reveals several novel aspects of the ghrelin gene and suggests that the ghrelin locus is far more complex than previously recognised.
Exploring the midgut transcriptome of Phlebotomus papatasi: comparative analysis of expression profiles of sugar-fed, blood-fed and Leishmania major-infected sandflies
Authors: Ramalho-Ortigão Marcelo , Jochim Ryan C , Anderson Jennifer M , Lawyer Phillip G , Pham Van-My , Kamhawi Shaden , Valenzuela Jesus G
Published: August 2007

Background

In sandflies, the blood meal is responsible for the induction of several physiologic processes that culminate in egg development and maturation. During blood feeding, infected sandflies are also able to transmit the parasite Leishmania to a suitable host. Many blood-induced molecules play significant roles during Leishmania development in the sandfly midgut, including parasite killing within the endoperitrophic space. In this work, we randomly sequenced transcripts from three distinct high quality full-length female Phlebotomus papatasi midgut-specific cDNA libraries from sugar-fed, blood-fed and Leishmania major-infected sandflies. Furthermore, we compared the transcript expression profiles from the three different cDNA libraries by customized bioinformatics analysis and validated these findings by semi-quantitative PCR and real-time PCR.

Results

Transcriptome analysis of 4010 cDNA clones resulted in the identification of the most abundant P. papatasi midgut-specific transcripts. The identified molecules included those with putative roles in digestion and peritrophic matrix formation, among others. Moreover, we identified sandfly midgut transcripts that are expressed only after a blood meal, such as microvilli associated-like protein (PpMVP1, PpMVP2 and PpMVP3), a peritrophin (PpPer1), trypsin 4 (PpTryp4), chymotrypsin PpChym2, and two unknown proteins. Of interest, many of these overabundant transcripts such as PpChym2, PpMVP1, PpMVP2, PpPer1 and PpPer2 were of lower abundance when the sandfly was given a blood meal in the presence of L. major.

Conclusion

This tissue-specific transcriptome analysis provides a comprehensive look at the repertoire of transcripts present in the midgut of the sandfly P. papatasi. Furthermore, the customized bioinformatic analysis allowed us to compare and identify the overall transcript abundance from sugar-fed, blood-fed and Leishmania-infected sandflies. The suggested upregulation of specific transcripts in a blood-fed cDNA library were validated by real-time PCR, suggesting that this customized bioinformatic analysis is a powerful and accurate tool useful in analysing expression profiles from different cDNA libraries. Additionally, the findings presented in this work suggest that the Leishmania parasite is modulating key enzymes or proteins in the gut of the sandfly that may be beneficial for its establishment and survival.
Obstacles for optimal tuberculosis case detection in primary health centers (PHC) in Sidoarjo district, East Java, Indonesia
Authors: Wahyuni Chatarina U , Budiono  , Rahariyani Lutfia Dwi , Sulistyowati Muji , Rachmawati Tety , Djuwari  , Yuliwati Sri , van der Werf Marieke J
Published: August 2007

Background

Pulmonary tuberculosis (TB) is a major health problem worldwide. Detection of the most infectious cases of tuberculosis – sputum smear-positive pulmonary cases – by passive case finding is an essential component of TB control. The district of Sidoarjo in East Java reported a low case detection rate (CDR) of 14% in 2003. We evaluated the diagnostic process for TB in primary health care centers (PHC) in Sidoarjo district to assess whether problems in identification of TB suspects or in diagnosing TB patients can explain the low CDR.

Methods

We performed interviews with the staff (general nurse, TB worker, laboratory technician, and head of health center) of the 25 PHCs of Sidoarjo district to obtain information about the knowledge of TB, health education practices, and availability of support services for TB diagnosis. The quality of the laboratory diagnosis was examined by providing 10 slides with a known result to the laboratory technicians for re-examination.

Results

Eighty percent of the nurses and 84% of the TB workers knew that cough >3 weeks can be a symptom of TB. Only 40% of the nurses knew the cause of TB, few could mention complications of TB and none could mention the duration of infectiousness after start of treatment. Knowledge of TB workers was much better. Information about how to produce a good sputum sample was provided to TB suspects by 76% of the nurses and 84% of the TB workers. Only few provided all information. Fifty-five percent of the 11 laboratory technicians correctly identified all positive slides as positive and 45% correctly identified 100% of the negative slides as negative. All TB workers, one general nurses and 32% of the laboratory technicians had received specific training in TB control. There has been no shortage of TB forms and laboratory materials in 96% of the PHCs.

Conclusion

The quality of the diagnostic process for TB at PHC in Sidoarjo district should be improved on all levels. Training in TB control of all general nurses and the laboratory technicians that have not received training would be a good first step to enhance diagnosis of TB and to improve the case detection rate.
Seroprevalence of parvovirus B19 IgG in children affected by juvenile idiopathic arthritis
Authors: Weissbrich Benedikt , Süß-Fröhlich Yvonne , Girschick Hermann J
Published: August 2007

Parvovirus (PV) B19 is the causative agent of the childhood disease erythema infectiosum. An association of PV B19 with chronic arthropathies, sometimes resembling rheumatoid arthritis or juvenile idiopathic arthritis (JIA), has repeatedly been described. Other studies, however, have failed to identify any such relationship. In order to study further whether there is a link between PV B19 and JIA, we determined the prevalence of PV B19 specific IgG antibodies in serum samples from children with rheumatoid diseases and compared it with the prevalence in unaffected children We reasoned that if there is an association between PV B19 and JIA, then the prevalence of PV B19 IgG in the children with JIA should be higher than in the control group. PV B19 IgG status was tested in 406 children with JIA and related diseases, and in 146 children constituting a control group. The percentage of PV B19 IgG positive children was not significantly elevated in the disease subgroups compared with age-matched control groups. In conclusion, our findings do not support the hypothesis that human parvovirus B19 is involved in the pathogenesis of JIA.
Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study
Authors: Le Maitre Christine L , Hoyland Judith A , Freemont Anthony J
Published: August 2007

Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1β, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD.
Model-based analysis of two-color arrays (MA2C)
Authors: Song Jun S , Johnson W Evan , Zhu Xiaopeng , Zhang Xinmin , Li Wei , Manrai Arjun K , Liu Jun S , Chen Runsheng , Liu X Shirley
Published: August 2007

A novel normalization method based on the GC content of probes is developed for two-color tiling arrays. The proposed method, together with robust estimates of the model parameters, is shown to perform superbly on published data sets. A robust algorithm for detecting peak regions is also formulated and shown to perform well compared to other approaches. The tools have been implemented as a stand-alone Java program called MA2C, which can display various plots of statistical analysis for quality control.
Interpretive advantages of 90°-phase wavelets: Part 2 — Seismic applications
Authors: Zeng Hongliu , Backus Milo M.
Published: August 2007

We examine field seismic data to test the benefits of 90°-phase wavelets in thin-bed interpretation that are predicted by seismic modeling in part 1 of this paper. In an interbedded sandstone-shale Miocene succession in the Gulf of Mexico basin, a 90°-phase shift of nearly zero-phase seismic data significantly improves lithologic and stratigraphic interpretation. A match between seismic and acoustic impedance (AI) profiles results in a better tie between seismic amplitude traces and lithology-indicative logs. Better geometric imaging of AI units that does not use dual-polarity seismic events results in easier and more accurate reservoir delineation. Less amplitude distortion and the stratigraphy-independent nature of thin-bed interference significantly improves stratigraphic resolution and seismic stratigraphic profiling. For a Ricker-like wavelet having small side lobes, stratigraphic resolution of 90°-phase data is considerably higher than that of zero-phase data. In this specific case, stratigraphic resolution of 90°-phase data is λ/4 (λ = wavelength), compared with λ/2 for its zero-phase counterpart. Stratal slices made from 90°-phase data show geomorphologic patterns of depositional systems with less noise and fewer interference fingerprints. A Permian Basin field provides a real-world example of porous zones in thin, high-frequency carbonate sequences that are better visualized with 90°-phase seismic data than with zero-phase data.
Risk of Injury and Fatality in Single Vehicle Rollover Crashes: Danger for the Front Seat Occupant in the “Outside Arc”
Authors: Jehle Dietrich , Kuebler Joseph , Auinger Peggy
Published: August 2007

Background: Rollover crashes are responsible for a large portion of motor vehicle occupant injuries and fatalities.

Objectives: To examine if there is an increased risk of injury or death for either front seat occupant depending on the direction the vehicle rolled over.

Methods: Between 1992 and 2002, crash data were collected and analyzed from the National Accident Sampling System Crashworthiness Data System (NASS/CDS) database of police reported tow‐away crashes in the United States. These data were limited to information concerning single vehicle crashes with right or left initial rollover, in which both driver and front seat passenger were present and secured with lap‐shoulder belts. The “outside arc” occupant was defined as the occupant who underwent the greatest degree of initial rotational torque during the rollover. Crashes involving sport utility vehicles (SUVs) were further evaluated for risks of injury or death based on the direction of the initial rollover. The location of roof crush and the types of injuries were also analyzed for these rollovers. This weighted database allows for the calculation of mortality and injury prevalence in the population.

Results: There was a significantly higher fatality rate for outside arc occupants than inside arc occupants in rollover crashes. The weighted percentage fatality for the occupant on the outside arc for all classes of light passenger vehicles was 0.38%, while the percentage fatality for the occupant on the inside arc was 0.23% (odds ratio [OR], 1.64; p = 0.04). As a subgroup, the SUV class showed a weighted outside arc fatality percentage of 0.23%, while the inside arc fatality percentage was 0.02% (OR, 10.69; p = 0.06). Additionally, in SUVs, the weighted percentage having an Injury Severity Score of 9–75 was 0.99% for the outside arc passengers but only 0.19% for the inside arc passengers (OR, 5.42; p = 0.04). Roof crush was located more commonly on the outside arc of the rollovers than on the inside arc (42% vs. 26.3%; p < 0.01). There was a trend toward increased head and neck injuries in the fatal rollover crashes when compared with fatalities in the entire NASS/CDS database (91% vs. 58%; p = 0.06).

Conclusions: The risk of death for outside arc occupants was higher than for inside arc occupants in rollovers. In addition, outside arc occupants in SUV rollover crashes were more likely to incur moderate or severe traumatic injuries. Roof crush occurs more commonly on the outside arc, and head and neck injuries were more prevalent in rollover crashes.