bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies
Authors: Ciaschini PM , Straus SE , Dolovich LR , Goeree RA , Leung KM , Woods CR , Zimmerman GM , Majumdar SR , Spadafora S , Fera LA , Lee HN 
Published: November 2008

Abstract

Background
Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis, as well as prevention of fractures and falls, are substantially underutilized. This paper outlines the protocol for a pragmatic randomised trial of a multifaceted community-based care program aimed at optimizing the evidence-based management of falls and fractures in patients at risk.

Design
6-month randomised controlled study.

Methods
This population-based study was completed in the Algoma District of Ontario, Canada a geographically vast area with Sault Ste Marie (population 78 000) as its main city. Eligible patients were allocated to an immediate intervention protocol (IP) group, or a delayed intervention protocol (DP) group. The DP group received usual care for 6 months and then was crossed over to receive the interventions. Components of the intervention were directed at the physicians and their patients and included patient-specific recommendations for osteoporosis therapy as outlined by the clinical practice guidelines developed by Osteoporosis Canada, and falls risk assessment and treatment. Two primary outcomes were measured including implementation of appropriate osteoporosis and falls risk management. Secondary outcomes included quality of life and the number of falls, fractures, and hospital admissions over a twelve-month period. The patient is the unit of allocation and analysis. Analyses will be performed on an intention to treat basis.

Discussion
This paper outlines the protocol for a pragmatic randomised trial of a multi-faceted, community-based intervention to optimize the implementation of evidence based management for patients at risk for falls and osteoporosis.

Trial Registration
This trial has been registered with clinicaltrials.gov (ID: NCT00465387)
The extent of the psychological impairment of prosthodontic outpatients at a German University Hospital
Authors: Ommerborn Michelle A , Hugger Alfons , Kruse Johannes , Handschel Jörg GK , Depprich Rita A , Stüttgen Ulrich , Zimmer Stefan , Raab Wolfgang HM 
Published: November 2008

Abstract

Background
Psychological factors are not only important in patients with temporomandibular disorders (TMDs), but also in patients suffering from tooth loss and/or in those awaiting prosthodontic care with fixed or removable dentures as several authors emphasize. The purpose of the present prospective observational study was to compare prosthodontic outpatients of the Department of Prosthodontics at the University of Duesseldorf and patients seeking care at the TMD/Orofacial Pain Outpatient Clinic (TMD/OFPOC) at the same university with respect to sociodemographic data, self-reported somatic complaints, and psychological impairment.

Methods
A total of 234 patients received two self-administered questionnaires including the Symptom-Check-List. Complete data have been obtained from 65 prosthodontic outpatients and 60 patients of the TMD/OFPOC.

Results
Results indicated statistically significant group differences regarding sociodemographic data and somatic complaints. Concerning the latter, in 11 of the 21 items, groups differed significantly and confirmed the absence of any mixing between the two outpatient clinics. Although the evaluation of psychological impairment revealed no significant group differences, in 21.9% of the prosthodontic outpatients and in 22.0% of the patients from the TMD/OFPOC, the extent of the determined psychological impairment was similar to that of psychotherapeutic outpatients; in 9.4% and 8.5% it was similar to that of psychotherapeutic inpatients, respectively.

Conclusion
Within the limitations of this study, in approximately one third of the evaluated patients of both the prosthodontic outpatient clinic and the TMD/OFPOC the psychological impairment reached values comparable to those of psychotherapeutic outpatients and psychotherapeutic inpatients. Therefore, the present findings emphasize the need to intensify the integration of psychosomatic aspects into dentistry and, in particular, to add psychological considerations to future German education plans.
Vertebral rotation measurement: a summary and comparison of common radiographic and CT methods
Authors: Lam Gabrielle C , Hill Doug L , Le Lawrence H , Raso Jim V , Lou Edmond H 
Published: November 2008

Abstract
Current research has provided a more comprehensive understanding of Adolescent Idiopathic Scoliosis (AIS) as a three-dimensional spinal deformity, encompassing both lateral and rotational components. Apart from quantifying curve severity using the Cobb angle, vertebral rotation has become increasingly prominent in the study of scoliosis. It demonstrates significance in both preoperative and postoperative assessment, providing better appreciation of the impact of bracing or surgical interventions. In the past, the need for computer resources, digitizers and custom software limited studies of rotation to research performed after a patient left the scoliosis clinic. With advanced technology, however, rotation measurements are now more feasible. While numerous vertebral rotation measurement methods have been developed and tested, thorough comparisons of these are still relatively unexplored. This review discusses the advantages and disadvantages of six common measurement techniques based on technology most pertinent in clinical settings: radiography (Cobb, Nash-Moe, Perdriolle and Stokes' method) and computer tomography (CT) imaging (Aaro-Dahlborn and Ho's method). Better insight into the clinical suitability of rotation measurement methods currently available is presented, along with a discussion of critical concerns that should be addressed in future studies and development of new methods.
Smad4 haploinsufficiency: a matter of dosage
Authors: Alberici Paola , Gaspar Claudia , Franken Patrick , Gorski Marcin M , de Vries Ingrid , Scott Rodney J , Ristimäki Ari , Aaltonen Lauri A , Fodde Riccardo 
Published: November 2008

Abstract

Background
The inactivation of tumor suppressor genes follows Alfred Knudson's 'two-hit' model: both alleles need to be inactivated by independent mutation events to trigger tumor formation. However, in a minority of tumor suppressor genes a single hit is sufficient to initiate tumorigenesis notwithstanding the presence of the wild-type allele, a condition known as haploinsufficiency. The SMAD4 gene is an intracellular mediator of the TGF-β and BMP signal transduction pathways and a tumor suppressor involved in pancreatic and colorectal tumorigenesis. In Smad4-mutant mouse models, haploinsufficiency characterizes the development of gastrointestinal polyps with initial retention of the wild-type allele and protein expression within the nascent tumors and in their direct microenvironment. Similarly, germline SMAD4 mutations are responsible for a subset of patients affected by juvenile polyposis syndrome, an autosomal dominant intestinal cancer syndrome. To date, the molecular and cellular consequences of SMAD4 haploinsufficiency on TGF-β and BMP signaling and on genome-wide gene expression have not been investigated.

Results
Here we show that, similar to previous observations in Smad4-mutant mouse models, haploinsufficiency characterizes a substantial fraction of the juvenile polyps arising in patients with germline SMAD4 mutations. Also, mouse embryonic and intestinal cells heterozygous for a targeted Smad4 null mutation are characterized by a corresponding 50% reduction of the Smad4 protein levels. Reporter assays revealed that mouse Smad4
+/- cells exert intermediate inhibitory effects on both TGF-β and BMP signaling. Genome-wide expression profiling analysis of Smad4
+/- and Smad4
-/- cells pinpointed a subset of dosage-dependent transcriptional target genes encompassing, among others, members of the TGF-β and Wnt signaling pathways. These SMAD4 dosage-dependent transcriptional changes were confirmed and validated in a subset of target genes in intestinal tissues from juvenile polyposis syndrome patients.

Conclusion

Smad4 haploinsufficiency is sufficient to significantly inhibit both TGF-β and BMP signal transduction and results in the differential expression of a broad subset of target genes likely to underlie tumor formation both from the mesenchymal and epithelial compartments. The results of our study, performed in normal rather than tumor cells where additional (epi-) genetic alterations may confound the analysis, are relevant for our understanding and elucidation of the initial steps underlying SMAD4-driven intestinal tumorigenesis.
High-efficiency Rosa26 knock-in vector construction for Cre-regulated overexpression and RNAi
Authors: Hohenstein Peter , Slight Joan , Ozdemir Derya Deniz , Burn Sally F , Berry Rachel , Hastie Nicholas D 
Published: November 2008

Abstract

Introduction
Rosa26 is a genomic mouse locus commonly used to knock-in cDNA constructs for ubiquitous or conditional gene expression in transgenic mice. However, the vectors generally used to generate Rosa26 knock-in constructs show instability problems, which have a severe impact on the efficiency of the system.

Results
We have optimized the cloning procedure to generate targeting vectors for Cre-regulated expression of constructs within several days with minimal hands-on time, thereby enabling high-throughput approaches. We demonstrate that transient expression of Cre still results in expression of the construct, as shown by the expression level and via functional assays. In addition to its well-established possibilities in expressing cDNA constructs, we show that the Rosa26 locus can be used to drive expression of functional miRNA constructs from its endogenous promoter.

Conclusion
We provide a new high-efficiency cloning system for Rosa26 knock-in constructs to express either cDNA or miRNA fragments. Our system will enable high-throughput approaches for controlled expression of cDNA or miRNA constructs, with the latter providing a potential high-speed alternative for conditional knock-out models.
The fungus Neurospora crassa displays telomeric silencing mediated by multiple sirtuins and by methylation of histone H3 lysine 9
Authors: Smith Kristina M , Kothe Gregory O , Matsen Cindy B , Khlafallah Tamir K , Adhvaryu Keyur K , Hemphill Melissa , Freitag Michael , Motamedi Mohammad R , Selker Eric U 
Published: November 2008

Abstract

Background
Silencing of genes inserted near telomeres provides a model to investigate the function of heterochromatin. We initiated a study of telomeric silencing in Neurospora crassa, a fungus that sports DNA methylation, unlike most other organisms in which telomeric silencing has been characterized.

Results
The selectable marker, hph, was inserted at the subtelomere of Linkage Group VR in an nst-1 (neurospora sir two-1) mutant and was silenced when nst-1 function was restored. We show that NST-1 is an H4-specific histone deacetylase. A second marker, bar, tested at two other subtelomeres, was similarly sensitive to nst-1 function. Mutation of three additional SIR2 homologues, nst-2, nst-3 and nst-5, partially relieved silencing. Two genes showed stronger effects: dim-5, which encodes a histone H3 K9 methyltransferase and hpo, which encodes heterochromatin protein-1. Subtelomeres showed variable, but generally low, levels of DNA methylation. Elimination of DNA methylation caused partial derepression of one telomeric marker. Characterization of histone modifications at subtelomeric regions revealed H3 trimethyl-K9, H3 trimethyl-K27, and H4 trimethyl-K20 enrichment. These modifications were slightly reduced when telomeric silencing was compromised. In contrast, acetylation of histones H3 and H4 increased.

Conclusion
We demonstrate the presence of telomeric silencing in Neurospora and show a dependence on histone deacetylases and methylation of histone H3 lysine 9. Our studies also reveal silencing functions for DIM-5 and HP1 that appear independent of their role in de novo DNA methylation.
Rapid analysis of heterogeneously methylated DNA using digital methylation-sensitive high resolution melting: application to the CDKN2B (p15) gene
Authors: Candiloro Ida LM , Mikeska Thomas , Hokland Peter , Dobrovic Alexander 
Published: November 2008

Abstract

Background
Methylation-sensitive high resolution melting (MS-HRM) methodology is able to recognise heterogeneously methylated sequences by their characteristic melting profiles. To further analyse heterogeneously methylated sequences, we adopted a digital approach to MS-HRM (dMS-HRM) that involves the amplification of single templates after limiting dilution to quantify and to determine the degree of methylation. We used this approach to study methylation of the CDKN2B (p15) cell cycle progression inhibitor gene which is inactivated by DNA methylation in haematological malignancies of the myeloid lineage. Its promoter region usually shows heterogeneous methylation and is only rarely fully methylated. The methylation status of CDKN2B can be used as a biomarker of response to treatment. Therefore the accurate characterisation of its methylation is desirable.

Results
MS-HRM was used to assess CDKN2B methylation in acute myeloid leukaemia (AML) samples. All the AML samples that were methylated at the CDKN2B promoter (40/93) showed varying degrees of heterogeneous methylation. Six representative samples were selected for further study. dMS-HRM was used to simultaneously count the methylated alleles and assess the degree of methylation. Direct sequencing of selected dMS-HRM products was used to determine the exact DNA methylation pattern and confirmed the degree of methylation estimated by dMS-HRM.

Conclusion
dMS-HRM is a powerful technique for the analysis of methylation in CDKN2B and other heterogeneously methylated genes. It eliminates both PCR and cloning bias towards either methylated or unmethylated DNA. Potentially complex information is simplified into a digital output, allowing counting of methylated and unmethylated alleles and providing an overall picture of methylation at the given locus. Downstream sequencing is minimised as dMS-HRM acts as a screen to select only methylated clones for further analysis.
Evidence for conserved DNA and histone H3 methylation reprogramming in mouse, bovine and rabbit zygotes
Authors: Lepikhov Konstantin , Zakhartchenko Valeri , Hao Ru , Yang Feikun , Wrenzycki Christine , Niemann Heiner , Wolf Eckhard , Walter Joern 
Published: November 2008

AbstractBackgroundIn mammals the parental genomes are epigenetically reprogrammed after fertilization. This reprogramming includes a rapid demethylation of the paternal (sperm-derived) chromosomes prior to DNA replication in zygotes. Such active DNA demethylation in the zygote has been documented for several mammalian species, including mouse, rat, pig, human and cow, but questioned to occur in rabbit.ResultsWhen comparing immunohistochemical patterns of antibodies against 5-methyl-cytosine, H3K4me3 and H3K9me2 modifications we observe similar pronuclear distribution and dynamics in mouse, bovine and rabbit zygotes. In rabbit DNA demethylation of the paternal chromosomes occurs at slightly advanced pronuclear stages. We also show that the rabbit oocyte rapidly demethylates DNA of donor fibroblast after nuclear transfer.ConclusionOur data reveal that major events of epigenetic reprogramming during pronuclear maturation, including mechanisms of active DNA demethylation, are apparently conserved among mammalian species.
Prospective study of physical activity and risk of postmenopausal breast cancer
Authors: Leitzmann Michael F , Moore Steven C , Peters Tricia M , Lacey James V , Schatzkin Arthur , Schairer Catherine , Brinton Louise A , Albanes Demetrius 
Published: November 2008

Abstract
Introduction
To prospectively examine the relation of total, vigorous and non-vigorous physical activity to postmenopausal breast cancer risk.

Methods
We studied 32,269 women enrolled in the Breast Cancer Detection Demonstration Project Follow-up Study. Usual physical activity (including household, occupational and leisure activities) throughout the previous year was assessed at baseline using a self-administered questionnaire. Postmenopausal breast cancer cases were identified through self-reports, death certificates and linkage to state cancer registries. A Cox proportional hazards regression was used to estimate the relative risk and 95% confidence intervals of postmenopausal breast cancer associated with physical activity.

Results
During 269,792 person-years of follow-up from 1987 to 1998, 1506 new incident cases of postmenopausal breast cancer were ascertained. After adjusting for potential risk factors of breast cancer, a weak inverse association between total physical activity and postmenopausal breast cancer was suggested (relative risk comparing extreme quintiles = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.21). That relation was almost entirely contributed by vigorous activity (relative risk comparing extreme categories = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.08). The inverse association with vigorous activity was limited to women who were lean (ie, body mass index <25.0 kg/m2: relative risk = 0.68; 95% confidence interval = 0.54 to 0.85). In contrast, no association with vigorous activity was noted among women who were overweight or obese (ie, body mass index ≥ 25.0 kg/m2: relative risk = 1.18; 95% confidence interval = 0.93 to 1.49; p for interaction = 0.008). Non-vigorous activity showed no relation to breast cancer (relative risk comparing extreme quintiles = 1.02; 95% confidence interval = 0.87 to 1.19; p for trend = 0.86). The physical activity and breast cancer relation was not specific to a certain hormone receptor subtype.

Conclusions
In this cohort of postmenopausal women, breast cancer risk reduction appeared to be limited to vigorous forms of activity; it was apparent among normal weight women but not overweight women, and the relation did not vary by hormone receptor status. Our findings suggest that physical activity acts through underlying biological mechanisms that are independent of body weight control.
Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury: a randomized controlled trial
Authors: Varelmann Dirk , Muders Thomas , Zinserling Jörg , Guenther Ulf , Magnusson Anders , Hedenstierna Göran , Putensen Christian , Wrigge Hermann 
Published: November 2008

Abstract
Introduction
Acute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI.

Methods
Forty-four pigs were randomly assigned to ALI resulting either from hydrochloric acid aspiration (HCl-ALI) or from increased intra-abdominal pressure plus intravenous oleic acid injections (OA-ALI) and were ventilated in PCV mode either with SB (PCV + SB) or without SB (PCV – SB). Cardiorespiratory variables were measured at baseline after induction of ALI and after 4 hours of treatment (PCV + SB or PCV – SB). Finally, density distributions and end-expiratory lung volume (EELV) were assessed by thoracic spiral computed tomography.

Results
PCV + SB improved arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) by a reduction in intrapulmonary shunt fraction in HCl-ALI from 27% ± 6% to 23% ± 13% and in OA-ALI from 33% ± 19% to 26% ± 18%, whereas during PCV – SB PaO2/FiO2 deteriorated and shunt fraction increased in the HCl group from 28% ± 8% to 37% ± 17% and in the OA group from 32% ± 12% to 47% ± 17% (P < 0.05 for interaction time and treatment, but not ALI type). PCV + SB also resulted in higher EELV (HCl-ALI: 606 ± 171 mL, OA-ALI: 439 ± 90 mL) as compared with PCV – SB (HCl-ALI: 372 ± 130 mL, OA-ALI: 192 ± 51 mL, with P < 0.05 for interaction of time, treatment, and ALI type).

Conclusions
SB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI.
Nonpharmacologic Strategies for Managing Common Chemotherapy Adverse Effects: A Systematic Review
Authors: Lotfi-Jam Kerryann , Carey Mariko , Jefford Michael , Schofield Penelope , Charleson Catherine , Aranda Sanchia 
Published: November 2008

Purpose Adverse effects of chemotherapy can be severe and can have a significant impact on a person's quality of life. With chemotherapy treatment increasingly administered in the ambulatory setting, there is a need for patients to be informed about effective self-care strategies to manage treatment adverse effects. Advice for patients needs to be based on evidence. This systematic review provides an overview of the intervention research in this area as well as an effectiveness review of nonpharmacologic (self-care) strategies evaluated in high-quality randomized controlled trials (RCTs). Methods An extensive literature search was conducted to identify RCTs relating to self-care strategies for reducing nausea/vomiting, constipation, diarrhea, fatigue, hair loss, or mucositis. Relevant studies published in peer-reviewed journals between 1980 and August 2007 were included. Study characteristics, results and methodologic quality were examined. High-quality RCTs were further analyzed to establish the effectiveness of specific self-care strategies. Results The search identified 77 RCTs. Findings from RCTs of reasonable quality provide limited support for cognitive distraction, exercise, hypnosis, relaxation, and systematic desensitization to reduce nausea and vomiting, psycho-education for fatigue, and scalp cooling to reduce hair loss. Conclusion Although some strategies seem promising, the quality of the RCTs was generally quite low, making it difficult to draw conclusions about the effectiveness of self-care strategies. Future studies require better design and reporting of methodologic issues to establish evidence-based self-care recommendations for people receiving chemotherapy.
Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme
Authors: Reardon David A. , Fink Karen L. , Mikkelsen Tom , Cloughesy Timothy F. , O'Neill Alison , Plotkin Scott , Glantz Michael , Ravin Paula , Raizer Jeffrey J. , Rich Keith M. , Schiff David , Shapiro William R. , Burdette-Radoux Susan , Dropcho Edward J. , Wittemer Sabine M. , Nippgen Johannes , Picard Martin , Nabors L. Burt 
Published: November 2008

Purpose Cilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence. Patients and Methods Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments. Results Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months. Conclusion Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.