bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Human Epithelial Stem/Progenitor Expansion by FOXM1
Authors: Gemenetzidis Emilios , Elena-Costea Daniela , Parkinson Eric K. , Waseem Ahmad , Wan Hong , Teh Muy-Teck
Published: November 2010

Stem cells are permanent residents of tissues and thought to be targets of cancer initiation. The frequent, and often early, upregulation of the FOXM1 transcription factor in the majority of human cancers suggests that it may participate in the initiation of human tumorigenesis. However, this hypothesis has not been tested. Herein, we show that targeting the ectopic expression of FOXM1 to the highly clonogenic cells of primary human keratinocytes with stem/progenitor cell properties, but not to differentiating cells, caused clonal expansion in vitro. We show, using a functional three-dimensional organotypic epithelial tissue regeneration system, that ectopic FOXM1 expression perturbed epithelial differentiation generating a hyperproliferative phenotype reminiscent of that seen in human epithelial hyperplasia. Furthermore, transcriptional expression analysis of a panel of 28 epithelial differentiation-specific genes reveals a role for FOXM1 in the suppression of epithelial differentiation. This study provides the first evidence that FOXM1 participates in an early oncogenic pathway that predisposes cells to tumorigenesis by expanding the stem/progenitor compartment and deregulating subsequent keratinocyte terminal differentiation. This finding reveals an important window of susceptibility to oncogenic signals in epithelial stem/progenitor cells prior to differentiation, and may provide a significant benefit to the design of cancer therapeutic interventions that target oncogenesis at its earliest incipient stage. Cancer Res; 70(22); 9515–26. ©2010 AACR.
Optimizing the Detection of Lung Cancer Patients Harboring Anaplastic Lymphoma Kinase (ALK) Gene Rearrangements Potentially Suitable for ALK Inhibitor Treatment
Authors: Camidge D. Ross , Kono Scott A. , Flacco Antonella , Tan Aik-Choon , Doebele Robert C. , Zhou Qing , Crino Lucio , Franklin Wilbur A. , Varella-Garcia Marileila
Published: November 2010

Purpose: Anaplastic lymphoma kinase (ALK) rearrangements, associated with sensitivity to an experimental ALK/MET inhibitor, occur in 3% to 5% of non–small cell lung cancers. Intratumoral fluorescence in situ hybridization (FISH) heterogeneity has been reported. We explored the heterogeneity basis, the requirements for accurately determining ALK FISH positivity, and the effect of enriching the tested population using clinical and molecular factors.

Experimental Design: Lung cancer patients were screened by ALK and MET FISH and for EGFR and KRAS mutations.

Results: Thirteen ALK-positive cases were identified from 73 screened patients. Gene copy number increases occurred together with classic rearrangements. All positive cases were adenocarcinomas, 12 were EGFR/KRAS wild-type, and 1 had a coexistent EGFR exon 20 mutation. No association with MET amplification occurred. ALK positivity was associated with <10–pack-year smoking status (P = 0.0004). Among adenocarcinomas, without KRAS or EGFR mutations, with <10–pack-year history, 44.8% of cases were ALK positive. ALK FISH positivity was heterogeneous, but mean values in tumor areas from ALK-positive patients (54% of cells; range, 22-87%) were significantly higher than in adjacent normal tissue or tumor/normal areas from ALK-negative patients (mean, 5-7%). Contiguous sliding field analyses showed diffuse heterogeneity without evidence of focal ALK rearrangements. One hundred percent sensitivity and specificity occurred when four or more fields (∼60 cells) were counted.

Conclusions: Intratumoral ALK FISH heterogeneity reflects technique, not biology. The clinical activity of ALK/MET inhibitors in ALK-positive patients probably reflects ALK, but not MET, activity. Prescreening by histology, EGFR/KRAS mutations, and smoking status dramatically increases the ALK-positive hit rate compared with unselected series. Clin Cancer Res; 16(22); 5581–90. ©2010 AACR.
Hypoexpression and Epigenetic Regulation of Candidate Tumor Suppressor Gene CADM-2 in Human Prostate Cancer
Authors: Chang Guimin , Xu Shuping , Dhir Rajiv , Chandran Uma , O'Keefe Denise S. , Greenberg Norman M. , Gingrich Jeffrey R.
Published: November 2010

Purpose: Cell adhesion molecules (CADM) comprise a newly identified protein family whose functions include cell polarity maintenance and tumor suppression. CADM-1, CADM-3, and CADM-4 have been shown to act as tumor suppressor genes in multiple cancers including prostate cancer. However, CADM-2 expression has not been determined in prostate cancer.

Experimental Design: The CADM-2 gene was cloned and characterized and its expression in human prostatic cell lines and cancer specimens was analyzed by reverse transcription-PCR and an immunohistochemical tissue array, respectively. The effects of adenovirus-mediated CADM-2 expression on prostate cancer cells were also investigated. CADM-2 promoter methylation was evaluated by bisulfite sequencing and methylation-specific PCR.

Results: We report the initial characterization of CADM-2 isoforms: CADM-2a and CADM-2b, each with separate promoters, in human chromosome 3p12.1. Prostate cancer cell lines, LNCaP and DU145, expressed negligible CADM-2a relative to primary prostate tissue and cell lines, RWPE-1 and PPC-1, whereas expression of CADM-2b was maintained. Using immunohistochemistry, tissue array results from clinical specimens showed statistically significant decreased expression in prostate carcinoma compared with normal donor prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and normal tissue adjacent to tumor (P < 0.001). Adenovirus-mediated CADM-2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. The decrease in CADM-2a mRNA in cancer cell lines correlated with promoter region hypermethylation as determined by bisulfite sequencing and methylation-specific PCR. Accordingly, treatment of cells with the demethylating agent 5-aza-2′-deoxycytidine alone or in combination with the histone deacetylase inhibitor trichostatin A resulted in the reactivation of CADM-2a expression.

Conclusions: CADM-2a protein expression is significantly reduced in prostate cancer. Its expression is regulated in part by promoter methylation and implicates CADM-2 as a previously unrecognized tumor suppressor gene in a proportion of human prostate cancers. Clin Cancer Res; 16(22); 5390–401. ©2010 AACR.
A Randomized Controlled, Phase 2 Trial of the Viral Serpin Serp-1 in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention
Authors: Tardif Jean-Claude , L'Allier Philippe L. , Grégoire Jean , Ibrahim Reda , McFadden Grant , Kostuk William , Knudtson Merril , Labinaz Marino , Waksman Ron , Pepine Carl J. , Macaulay Colin , Guertin Marie-Claude , Lucas Alexandra
Published: November 2010

Background—

Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus–derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention.

Methods and Results—

This double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention randomly assigned to Serp-1 at doses of 5 μg/kg (n=19) or 15 μg/kg (n=17) or to placebo (n=12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours later. Patients were assessed for safety (primary objective) and efficacy outcomes, including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months. Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (
P
<0.05) and in creatine kinase-MB levels at 8, 16, and 24 hours after dose (
P
<0.05). The composite of death, myocardial infarction, or coronary revascularization occurred in 2 of 12 patients with placebo, 5 of 19 in the low-dose group, and none of 17 patients with the high-dose (
P
=0.058). Intravascular ultrasound did not detect changes in neointimal hyperplasia among groups.

Conclusions—

This is the first study of a viral serpin demonstrating its safety in ACS patients. The significant reduction in myocardial damage biomarkers supports further assessment of Serp-1 in ACS patients undergoing stent deployment.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00243308.
Preparing Globally Competent Teachers: A New Imperative for Teacher Education
Authors: Zhao Yong
Published: November 2010

Globalization is one of the most powerful forces that will shape the future world in which our children will live. How to prepare our children to live successfully in this world has become a challenging question for education. This article discusses the challenges globalization presents to education and the implications for teacher education.
Transforming Teacher Education to Reform America’s P-20 Education System
Authors: Futrell Mary Hatwood
Published: November 2010

Moving beyond reform, teacher education programs need to be transformed to better prepare teachers, school counselors, and administrators to teach, guide, and lead in this complex society. Educators must have the skills, knowledge, and commitment to be part of the leadership team that assumes the responsibility for carrying the mantra of the transformational process. This mantra will require faculty to remove the silos within schools and across university campuses and collaborate with one another and key community members to prepare prospective educators who will inherit the responsibility for redesigning America’s schools for the realities of more interactive, interdisciplinary learning environments. This article briefly reviews the history of reform and describes several potentially transformative initiatives currently under way to redefine and strengthen teacher education programs.
The Positioning of Sustainability within Residential Property Marketing
Authors: Kriese Ulrich , Scholz Roland W.
Published: November 2010

This article investigates the evolution of sustainability positioning in residential property marketing to shed light on the specific role and responsibility of housebuilders and housing investors in urban development. To this end, an analysis is made of housing advertisements published in Basel, Switzerland, over a period of more than 100 years. The paper demonstrates how to draw successfully on advertisements to discern sustainability patterns in housing, using criteria situated along the dimensions building, location and people. Cluster analysis allows five clusters of sustainability positioning to be described—namely, good location, green building, comfort living, pre-sustainability and sustainability. Investor and builder types are differently located in these clusters. Location emerges as an issue which, to a large extent, is advertised independently from other sustainability issues.
An Analysis of the Housing Redevelopment Process in Korea through the Lens of the Transaction Cost Framework
Authors: Cho Cheol-Joo
Published: November 2010

This paper applies the transaction cost framework to the analysis of the housing redevelopment process in Korea. The housing redevelopment process involves various identifiable transactions and cost-incurring hazards which originate from uncertainty about development potential and effects, interdependencies and the consequent strategic behaviours of relevant parties. Responding to the characteristics of the transactions and hazards, various forms of governance structure are institutionalised. The extant governance mechanisms fit neither perfect market nor pure hierarchy. Rather, hybrid forms of governance spanning the public and private spheres are aligned with the relevant transactions. On the other hand, a remediableness test indicates that different governance mechanisms which seem more efficient than the current ones can be identified for each stage of housing redevelopment. This finding marks a superb potential of the transaction cost approach for assessing institutional efficiency that the Pigouvian approach does not have.
Empirical study on drainage stack terminal water velocity
Authors: Cheng CL , Liao WJ , He KC , Lin JL
Published: November 2010

A building drainage network is an essential provision of each developed city all over the world. The terminal velocity at discharging drainage stack is a crucial issue as it provides the permitted flow rate of a building drainage system. The National Plumbing Code (NPC) of the US has specified the permitted flow rate for drainage systems. Mathematical expressions for terminal velocity were reported in research studies since the 1920s but discrepancies among calculations remained. This study proposes an empirical approach in determining the terminal velocity in a drainage stack using the air pressure distribution mechanism. New experimental observations of the stack terminal velocity using a digital high-speed video camera were presented as a validation database. The proposed model was validated in terms of the measured terminal velocities and the locations of the maximum air pressure in a discharging stack at a steady water flow rate (1.0, 2.0, 3.0 and 4.0 L/s). This article offers an empirical approach and validation for terminal velocity instead of using the existing deductive approach.

Practical applications: This article proposes an empirical approach with experimental validation for terminal velocity at a drainage stack. New evidence presented would lead to a review of the terminal velocity in drainage stacks in future drainage network designs. Due to the importance of terminal velocity, it is anticipated that this result would be used to lead the new technical development of building drainage system.
Coordination of Autophagy and the Proteasome in Resolving Endoplasmic Reticulum Stress
Authors: Chen X. , Yin X.-M.
Published: November 2010

Macroautophagy is a cellular degradation mechanism that involves the delivery of cytosolic components (macromolecules or organelles) by the autophagosome to the lysosome for degradation. In mammalian cells, macroautophagy and the ubiquitin proteasome system are 2 major mechanisms to eliminate abnormal proteins accumulated in pathological conditions. Here, the coordination of the 2 pathways to alleviate endoplasmic reticulum stress is reviewed. Also discussed is the regulatory role of macroautophagy and proteasome activity in cell survival and death, as well as the recent discoveries leading to novel strategies of simultaneous control of the proteasome and autophagy activity in anticancer treatment.
Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior
Authors: Kiupel M. , Webster J. D. , Bailey K. L. , Best S. , DeLay J. , Detrisac C. J. , Fitzgerald S. D. , Gamble D. , Ginn P. E. , Goldschmidt M. H. , Hendrick M. J. , Howerth E. W. , Janovitz E. B. , Langohr I. , Lenz S. D. , Lipscomb T. P. , Miller M. A. , Misdorp W. , Moroff S. , Mullaney T. P. , Neyens I. , O’Toole D. , Ramos-Vara J. , Scase T. J. , Schulman F. Y. , Sledge D. , Smedley R. C. , Smith K. , W. Snyder P. , Southorn E. , Stedman N. L. , Steficek B. A. , Stromberg P. C. , Valli V. E. , Weisbrode S. E. , Yager J. , Heller J. , Miller R.
Published: November 2010

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.
Anterior Cruciate Ligament Allograft Surgery
Authors: Sikka Robby S. , Narvy Steven J. , Vangsness C. Thomas
Published: November 2010

Background: There has been much controversy regarding the effects of sterilization techniques and graft history on the structural integrity of allograft ligaments used in reconstruction of the anterior cruciate ligament. The purpose of this review was to comprehensively examine anterior cruciate ligament allograft studies published in the last decade to evaluate the extent to which tissue source, tissue processing techniques, and donor age are reported.

Methods: The authors reviewed 202 articles published from 1999 through November 2009, of which 68 retrospective, prospective, biomechanical, and histology studies evaluating 4689 allografts were included.

Results: The majority of studies do not accurately report key elements of graft history including tissue bank, processing or sterilization technique, or donor age. Underreporting was particularly prominent in clinical studies as compared with basic science studies. Limited reporting of allograft processing, allograft source, and donor age raises serious questions regarding the generalizability of published studies of allograft tissue for anterior cruciate ligament reconstruction.

Conclusion/Clinical Relevance: Orthopaedic surgeons who use allograft tissue must understand the tissue treatments being used (ie, preservation methods, chemical and sterilization processes) to best inform their patients regarding the risks, benefits, and long-term outcomes when such tissues are used. A complete understanding of the implanted tissue, as well as surgeon and recipient demographics, is necessary to ensure appropriate and predictable long-term outcomes.
Dynamic Mechanical Properties and Characterization of Inorganic Particulate-filled Polymer Composites
Authors: Liang J.Z.
Published: November 2010

On the basis of Ashelby’s method and Mori’s work, a simplified equation describing the relationship between the storage modulus and filler volume fraction for polymer composites filled with inorganic particles was proposed. The dynamic mechanical properties of the low-density polyethylene composites filled with glass beads were measured using a Du Pont dynamical mechanical analysis instrument in temperature range from —150°C to 100°C. It was found that the storage modulus increased roughly nonlinearly with an increase of the glass bead weight fraction. The relative storage modulus of these composites was estimated by means of this equation under experimental conditions, and compared with the experimental data. The results showed that the predictions of this equation were roughly consistent with the measured data and were close to the estimations of the equations published in literature. Furthermore, this equation was also verified by quoting some experimental data of quartz powder filled epoxy composites from reference.
To Intend to but Not Being Able to
Authors: Wiklund-Gustin Lena
Published: November 2010

Purpose: Patients who frequently consult the health care system are supposed to cause great economic costs, and they also trouble the health care staff, as it seems as if there are no interventions that will help and keep them healthy. The researcher assumes that these patients attend for a reason and that they attend frequently because they, from a holistic point of view, do not get their health care needs fulfilled. This article aims to describe how frequent attenders experience their suffering and their encounter with the health care system. Design and method: The study has an inductive hermeneutic design. Interviews with persons identified as frequent attenders were analyzed by means of a hermeneutic inquiry with three interpretive steps: naive reading, structural analysis, and critical reflection. Findings: Patients are constantly striving to be and become healthy, to be of use, and to please others. The patients do not attend until suffering is experienced as unbearable. The patients experience, however, that health care staff do not understand their situation. Patients experience feelings of mistrust and rejection, which increases suffering. Conclusion: Holistic care could be a means to relieve suffering and, as a consequence, reduce attendance.
Simulating the Dynamics of Subsistence Fishing Communities
Authors: Cleland Deborah , Dray Anne , Perez Pascal , Cruz-Trinidad Annabelle , Geronimo Rollan
Published: November 2010

REEFGAME is a computer-assisted role-playing game that explores the interactions among management strategies, livelihood options, and ecological degradation in subsistence fishing communities. The tool has been successfully used in the Philippines and a variety of student workshops. In the field, REEFGAME operated as a two-way learning tool, helping local fishers better understand their collective impacts on the marine ecosystem and providing researchers with insights into fisher livelihood strategies. This demonstrates the game’s ability to serve as powerful springboard for social learning and discussion among stakeholders, while providing useful scientific insights into decision-making processes. Although not specifically designed for the purpose, REEFGAME has also been used in the university setting to facilitate student engagement and demonstrate a range of social and ecological concepts.
The Political Economy of Wildlife Conservation and Decline in Kenya
Authors: Kabiri Ngeta
Published: November 2010

Wildlife is the backbone of tourism in Kenya, one of the leading foreign exchange earners for the country. Although wildlife is declining, poverty among communities hosting this wildlife remains endemic. Using field data and secondary literature, this article examines the extent to which the existing wildlife conservation regime must be considered responsible for the associated issues of wildlife decline and community poverty. The author contends that the interests of landowners (both community and private) must be meaningfully incorporated into wildlife conservation planning in order for both impacted communities and wildlife management to be sustainable. The article proposes a rethinking of the wildlife governance philosophy in this respect and sets out pragmatic policy suggestions on how to reform wildlife management for conservation in Kenya built on securing more benefits for the communities that shoulder the burden of conservation.
The YouTube Indian: Portrayals of Native Americans on a viral video site
Authors: Kopacz Maria , Lee Lawton Bessie
Published: November 2010

Mainstream media messages contain limited, distorted and negative images of Native Americans, thus promoting continued ethnic marginalization. Community-oriented online venues like the viral video sites have opened up new platforms for depiction. This study employed a quantitative content analysis to examine a sample of YouTube videos relating to Native Americans. The findings reveal a number of promising patterns, suggesting that messages broadcast by viral video sites may depart from the rigid stereotypical depictions of Native Americans in traditional media.
Mechanical Joint Laxity Associated With Chronic Ankle Instability
Authors: Cordova Mitchell L. , Sefton JoEllen M. , Hubbard Tricia J.
Published: November 2010

Context:

Lateral ankle sprains can manifest into chronic mechanical joint laxity when not treated effectively. Joint laxity is often measured through the use of manual stress tests, stress radiography, and instrumented ankle arthrometers.

Purpose:

To systematically review the literature to establish the influence of chronic ankle instability (CAI) on sagittal and frontal plane mechanical joint laxity.

Data Sources:

Articles were searched with MEDLINE (1966 to October 2008), CINAHL (1982 to October 2008), and the Cochrane Database of Systematic Reviews (to October 2008) using the key words chronic ankle instability and joint laxity, functional ankle instability and joint laxity, and lateral ankle sprains and joint laxity.

Study Selection:

To be included, studies had to employ a case control design; mechanical joint laxity had to be measured via a stress roentogram, an instrumented ankle arthrometer, or ankle/foot stress-testing device; anteroposterior inversion or eversion ankle-subtalar joint complex laxity had to be measured; and means and standard deviations of CAI and control groups had to be provided.

Data Extraction:

One investigator assessed each study based on the criteria to ensure its suitability for analysis. The initial search yielded 1378 potentially relevant articles, from which 8 were used in the final analysis. Once the study was accepted for inclusion, its quality was assessed with the PEDro scale.

Data Synthesis:

Twenty-one standardized effect sizes and their 95% confidence intervals were computed for each group and dependent variable. CAI produced the largest effect on inversion joint laxity; 45% of the effects ranged from 0.84 to 2.61. Anterior joint laxity measures were influenced second most by CAI (effects, 0.32 to 1.82). CAI had similar but less influence on posterior joint laxity (effects, −0.06 to 0.68) and eversion joint laxity (effects, 0.03 to 0.69).

Conclusion:

CAI has the largest effect with the most variability on anterior and inversion joint laxity measurements, consistent with the primary mechanism of initial injury.
Medial Impingement of the Ankle in Athletes
Authors: Manoli Arthur
Published: November 2010

Context:

Medial impingement syndrome of the ankle is common in the athletic population. A marginal osteophyte on the leading edge of the medial talar facet and a corresponding “kissing” osteophyte on the tibia, in front of the medial malleolus, may abut and cause pain and limited dorsiflexion.

Background:

Palpation of the talar osteophyte and standard imaging—especially, the oblique view of the foot—are useful in making the diagnosis. Surgical removal of the osteophyte may be necessary.

Conclusions:

Ankle impingement is commonly seen in running and jumping sports, especially if the athlete has a subtle cavus foot. It may be associated with ankle instability, osteochondritis dissecans of the talus, and stress fractures of the foot.
Turf Toe
Authors: McCormick Jeremy J. , Anderson Robert B.
Published: November 2010

Context:

Despite an increasing awareness of turf toe injury, confusion still exists regarding the anatomy, mechanism, diagnosis, and treatment of this hyperextension injury to the hallux metatarsophalangeal (MTP) joint.

Evidence Acquisition:

This article reviews the anatomy, diagnosis, and treatment algorithm for turf toe injury by reviewing relevant studies and presenting information useful to clinicians, therapists, and athletic trainers. A literature search was performed by a review of PubMed and OVID articles published from 1976 to July 2010.

Results:

Grade I injury is a sprain or attenuation of the plantar capsular ligamentous complex of the hallux MTP joint; athletes are typically able to return to play as tolerated. Grade II injury is a partial rupture of the plantar soft tissue structures of the hallux MTP joint, typically requiring about 2 weeks to recover. Grade III injury is a complete rupture of the plantar structures of the hallux MTP joint, requiring at least 10 to 16 weeks to recover. Some complete ruptures require surgical repair.

Conclusion:

With accurate diagnosis, athletes can have an appropriate treatment plan, and their expectations can be tempered to the degree of injury. Careful management may allow successful return to play at a preinjury level of participation.
Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization
Authors: Jiang Shuxian , Alberich-Jorda Meritxell , Zagozdzon Radoslaw , Parmar Kalindi , Fu Yigong , Mauch Peter , Banu Naheed , Makriyannis Alexandros , Tenen Daniel G. , Avraham Shalom , Groopman Jerome E. , Avraham Hava Karsenty
Published: November 2010

Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB1 and CB2) and the enzymes involved in their biosynthesis and degradation. However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB2 receptors are expressed in human and murine HSPCs. On ligand stimulation with CB2 agonists, CB2 receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways. In vivo, the CB2 agonist AM1241 induced mobilization of murine HSPCs with short- and long-term repopulating abilities. In addition, granulocyte colony-stimulating factor -induced mobilization of HSPCs was significantly decreased by specific CB2 antagonists and was impaired in Cnr2−/− cannabinoid type 2 receptor knockout mice. Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB2/CB2 agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs. Thus, CB2 agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.
Effectiveness of 10 polymorphic microsatellite markers for parentage and pedigree analysis in plateau pika (Ochotona curzoniae)
Authors: Li Kexin , Geng Jianing , Qu Jiapeng , Zhang Yanming , Hu Songnian
Published: November 2010

Background

The plateau pika (Ochotona curzoniae) is an underground-dwelling mammal, native to the Tibetan plateau of China. A set of 10 polymorphic microsatellite loci has been developed earlier. Its reliability for parentage assignment has been tested in a plateau pika population. Two family groups with a known pedigree were used to validate the power of this set of markers.

Results

The error in parentage assignment using a combination of these 10 loci was very low as indicated by their power of discrimination (0.803 - 0.932), power of exclusion (0.351 - 0.887), and an effectiveness of the combined probability of exclusion in parentage assignment of 99.999%.

Conclusion

All the offspring of a family could be assigned to their biological mother; and their father or relatives could also be identified. This set of markers therefore provides a powerful and efficient tool for parentage assignment and other population analyses in the plateau pika.
Associations between VO2maxand vitality in older workers: a cross-sectional study
Authors: Strijk Jorien E , Proper Karin I , Klaver Linda , van der Beek Allard J , van Mechelen Willem
Published: November 2010

Background

To prevent early exit from work, it is important to study which factors contribute to healthy ageing. One concept that is assumed to be closely related to, and therefore may influence healthy ageing, is vitality. Vitality consists of both a mental and a physical component, and is characterised by a perceived high energy level, decreased feelings of fatigue, and feeling fit. Since VO2max gives an indication of one's aerobic fitness, which can be improved by increased levels of physical activity, and because feeling fit is one of the main characteristics of vitality, it is hypothesised that VO2max is related to vitality. Therefore, the aim of this study was to investigate the associations between VO2max and vitality.

Methods

In 427 older workers (aged 45 + years) participating in the Vital@Work study, VO2max was estimated at baseline using the 2-km UKK walk test. Vitality was measured by both the UWES Vitality Scale and the RAND-36 Vitality Scale. Associations were analysed using linear regression analyses.

Results

The linear regression models, adjusted for age, showed a significant association between VO2max and vitality measured with the RAND-36 Vitality Scale (β = 0.446; 95% CI: 0.220-0.673). There was no significant association between VO2max and vitality measured with the UWES (β = -0.006; 95% CI:-0.017 - 0.006), after adjusting for age, gender and chronic disease status.

Conclusions

VO2max was associated with a general measure of vitality (measured with the RAND-36 Vitality Scale), but not with occupational health related vitality (measured with the UWES Vitality Scale). The idea that physical exercise can be used as an effective tool for improving vitality was supported in this study.

Trial registration

NTR1240
Aromatase and 5-alpha Reductase Gene Expression: Modulation by Pain and Morphine Treatment in Male Rats
Authors: Aloisi Anna Maria , Ceccarelli Ilaria , Fiorenzani Paolo , Maddalena Melinda , Rossi Alessandra , Tomei Valentina , Sorda Giuseppina , Danielli Barbara , Rovini Michele , Cappelli Andrea , Anzini Maurizio , Giordano Antonio
Published: November 2010

Background:

The steroid hormone testosterone has been found to be greatly reduced by opioids in different experimental and clinical conditions. The purpose of this study on male rats was to determine the effects of a single injection of morphine (5 mg/Kg) on persistent pain (formalin test) and the single or combined effects on p450-aromatase and 5-alpha reductase type 1 mRNA expression in the brain, liver and testis. Testosterone was determined in the plasma and in the brain, morphine was assayed in the plasma.

Results:

In the morphine-treated rats, there were increases of 5-alpha reductase mRNA expression in the liver and aromatase mRNA expression in the brain and gonads. Morphine was detected in the blood of all morphine-treated rats even though there were no clear analgesic affects in the formalin-treated animals three hours after treatment. Testosterone was greatly reduced in the plasma and brain in morphine-treated subjects.

Conclusions:

It appears that morphine administration can induce long-lasting genomic effects in different body areas which contribute to the strong central and peripheral testosterone levels. These changes were not always accompanied by behavioral modifications.
Autotaxin and Lysophosphatidic Acid1 receptor-Mediated Demyelination of Dorsal Root Fibers by Sciatic Nerve Injury and Intrathecal Lysophosphatidylcholine
Authors: Nagai Jun , Uchida Hitoshi , Matsushita Yosuke , Yano Ryo , Ueda Mutsumi , Niwa Masami , Aoki Junken , Chun Jerold , Ueda Hiroshi
Published: November 2010

Background:

Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination.

Results:

In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient ( Lpar1−/−) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin ( atx+/−), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/− or Lpar1−/− mice.

Conclusions:

These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain.
Additional funding mechanisms for Public Hospitals in Greece: the case of Chania Mental Health Hospital
Authors: Rentoumis Anastasios , Mantzoufas Nikolaos , Kouris Gavriil , Golna Christina , Souliotis Kyriakos
Published: November 2010

Objectives

To investigate whether the long term lease of public hospital owned land could be an additional financing mechanism for Greek public (mental) health hospitals.

Methods

We performed a financial analysis of the official 2008 data of a case - study hospital (Mental Health Hospital of Chania). We used a capital budgeting approach to investigate whether value is created for the public hospital by engaging its assets in a project for the development of a private renal dialysis Unit.

Results

The development of the private unit in hospital owned land is a good investment decision, as it generates high project Net Present Value and Internal Rate of Return. When the project commences generating operating cash flows, nearly €400.000 will be paid annually to the Mental Health Hospital of Chania as rent, thereby gradually decreasing the annual deficit of the hospital.

Conclusions

Revenue generated from the long term lease of public hospital land is crucial to gradually eliminate hospital deficit. The Ministry of Health should encourage similar forms of Public Private Partnerships in order to ensure the sustainability of public (mental) hospitals.
The Rab GTPase Ypt7 is linked to retromer-mediated receptor recycling and fusion at the yeast late endosome
Authors: Balderhaar Henning J. kleine , Arlt Henning , Ostrowicz Clemens , Bröcker Cornelia , Sündermann Frederik , Brandt Roland , Babst Markus , Ungermann Christian
Published: November 2010

Organelles of the endomembrane system need to counterbalance fission and fusion events to maintain their surface-to-volume ratio. At the late mammalian endosome, the Rab GTPase Rab7 is a major regulator of fusion, whereas the homologous yeast protein Ypt7 seems to be restricted to the vacuole surface. Here, we present evidence that Ypt7 is recruited to and acts on late endosomes, where it affects multiple trafficking reactions. We show that overexpression of Ypt7 results in expansion and massive invagination of the vacuolar membrane, which requires cycling of Ypt7 between GDP- and GTP-bound states. Invaginations are blocked by ESCRT, CORVET and retromer mutants, but not by autophagy or AP-3 mutants. We also show that Ypt7–GTP specifically binds to the retromer cargo-recognition subcomplex, which – like its cargo Vps10 – is found on the vacuole upon Ypt7 overproduction. Our data suggest that Ypt7 functions at the late endosome to coordinate retromer-mediated recycling with the fusion of late endosomes with vacuoles.
Prolonged Propofol Use in a Critically III Pregnant Patient
Authors: Tajchman Sharla K , Bruno Jeffrey J
Published: November 2010

Objective:

To describe the prolonged use of propofol for sedation of a critically ill pregnant patient in her second trimester.

Case Summary:

A 20-year-old pregnant woman at 14 weeks' gestation with non-Hodgkin's lymphoma required intubation and mechanical ventilation secondary to tumor-related airway obstruction. Immediately after intubation, propofol was initiated for sedation and maintained for 51 days with only one 5-day interruption in therapy. Over the course of the patient's stay in the intensive care unit, systemic chemotherapy was administered, resulting in a reduction in tumor burden and allowing for successful extubation. Ultimately, the fetus was deemed nonviable and the pregnancy was terminated.

Discussion:

Propofol is an intravenous anesthetic agent commonly used for the sedation of mechanically ventilated patients and is the only sedative agent that carries a pregnancy category B rating. Fetal outcomes following long-term use of propofol during the first trimester have not been formally evaluated and few reports of propofol use outside of early pregnancy termination, outpatient procedures, or parturition exist in the medical literature. Our patient required early termination of pregnancy; however, we were unable to determine whether fetal loss was a result of propofol use, chemotherapy administration, the use of other pharmacologic agents, or perhaps a combined effect.

Conclusions:

Despite propofol's pregnancy category B rating, data are lacking in humans regarding its safe use during pregnancy and long-term developmental outcomes in children after exposure to propofol in utero. The safety of propofol as a sedative agent for critically ill pregnant patients remains unknown.
Assessment and mitigation of human-lion conflict in West and Central Africa
Authors: Bauer Hans , de Iongh Hans , Sogbohossou Etotepe
Published: November 2010

The lion (Panthera leo) is most threatened in West and Central Africa; livestock encroachment and indiscriminate killing of lions are the main threats. Human-lion conflict mitigation is therefore key to persistence. Several experiments were carried out in the region to assess and mitigate human-lion conflict. In Pendjari National Park in Benin, enclosures of clay instead of the usual thorny branches reduced depredation figures by half. Around the Niger side of ‘W’ National Park, depredation was estimated at US$138 per household per year and occurred mostly while grazing; people identified improved herding as the most appropriate measure. A livestock corridor through a chain of protected areas has helped reduce conflict in Benoue National Park, Cameroon. Close monitoring and enclosure improvements reduced depredation from 9 to 0 attacks in enclosures and from 60 to 18 on the pastures of six villages around Waza National Park, Cameroon. Cases in Chad and Guinea identified yet other mitigation measures, including the use of dogs, sensitisation over rural radio and using relevant Sourats from the Koran; data on effectiveness are lacking, however. These projects illustrate a varied suite of mitigation options and demonstrate that mitigation can be effective if the method is judiciously chosen and adapted to local circumstances.
Transportation Accident Investigation: The Development of Human Factors Research and Practice
Authors: Coury Bruce G. , Ellingstad Vernon S. , Kolly Joseph M.
Published: November 2010

This chapter explores the history of accident investigation and shows how the quest for understanding the multitude of physical, environmental, and behavioral factors found in transportation accidents has profoundly influenced views of human behavior and performance. The chapter also explores how a multidisciplinary approach to accident investigation has been influenced by a human factors perspective on transportation safety. The chapter concludes with a discussion of what recent research at the National Transportation Safety Board suggests may be the future for accident investigation.
Human Supervisory Control Challenges in Network-Centric Operations
Authors: Cummings Mary L. , Bruni Sylvain , Mitchell Paul J.
Published: November 2010

Network-centric operations (NCOs), envisioned for future command and control systems in military and civilian settings, must be supported by sophisticated automated systems, so human-computer interactions are an important aspect of overall system performance. This chapter identifies 10 human supervisory control challenges that could significantly impact operator performance in NCOs: information overload, attention allocation, decision biases, supervisory monitoring of operators, distributed decision making through team coordination, trust and reliability, the role of automation, adaptive automation, multimodal technologies, and accountability. NCOs will bring increases in the number of information sources, volume of information, and operational tempo with significant uncertainty, all of which will place higher cognitive demands on operators. Thus, it is critical that NCO research focuses not only on technological innovations but also on the strengths and limitations of human-automation interaction in a complex system.
From Intention to Input: Motor Cognition, Motor Performance, and the Control of Technology
Authors: McLaughlin Anne Collins , Simon Dominic A. , Gillan Douglas J.
Published: November 2010

Fundamental knowledge of motor cognition is an important component in a human factors repertoire, and this chapter serves as a guide to the history, theory, and application of motor cognition research.“From intention to input” captures the scope of this chapter in that cognitive theories of motor control, neural control of movement, and the effects of feedback on movement are all discussed. The chapter progresses from an overview and history of motor cognition theories down to the neural basis for movement, then to an application of these theories via the study of specific actions. From there, rooted in the scientist-practitioner paradigm of human factors, the chapter covers applied considerations for designing control tasks and their associated inputs, taking into account individual differences in motor cognition and control and identifying critical issues in designing for input. General, applied guidelines are provided for use with current and future systems that have a motor cognition component.
Human Performance in Space
Authors: Jones Patricia M.
Published: November 2010

Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration-from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of longduration spaceflight) affects crew performance and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculoskeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from the National Aeronautics and Space Administration.