bluuebunny/crossref_metadata_2025 huggingface dataset:
The Coevolution of Institutional Entrepreneurship: A Tale of Two Theories
Authors: Pacheco Desirée F. , York Jeffrey G. , Dean Thomas J. , Sarasvathy Saras D.
Published: March 2010

This article provides a review and analysis of institutional entrepreneurship research with a focus on the emergence of this literature within two largely divergent streams: sociology-based institutional theory and economics-based institutional economics. The authors completed a review of 141 articles from these concurrent, but unlinked, research streams to understand how their integration might contribute to the further understanding of institutional entrepreneurship. Each stream is reviewed on its respective approaches to the following topics: the nature of the institutional entrepreneur, the types of institutions addressed, the determinants of institutional entrepreneurship, the mechanisms used in the process, and the empirical focus of each stream. The article recommends greater assimilation of the two streams and discusses specific opportunities for conceptual integration. Finally, the article offers an agenda for incorporating entrepreneurship research into the study of institutional entrepreneurship. Findings from this review suggest that while institutional economics focuses mostly on the antecedents and outcomes of institutional entrepreneurship, the institutional theory perspective is more concerned with the process and mechanisms that drive such change. The authors also suggest that entrepreneurship theory can greatly advance our understanding of institutional entrepreneurship by informing whether and how opportunities for institutional change are recognized, discovered, and created, as well as by providing insights on the antecedents and mechanisms of such activity. Most important, integrating the unique perspectives and domains of institutional theory, institutional economics, and entrepreneurship research in the study of institutional entrepreneurship provides substantial opportunity for expanding our understanding of the concept and its implications.
Shoe-Surface Friction Influences Movement Strategies during a Sidestep Cutting Task
Authors: Dowling Ariel V. , Corazza Stefano , Chaudhari Ajit M. W. , Andriacchi Thomas P.
Published: March 2010

Background

Increasing the coefficient of friction of the shoe-surface interaction has been shown to lead to increased incidence of anterior cruciate ligament (ACL) injuries, but the causes for this increase are unknown. Previous studies indicate that specific biomechanical measures during landing are associated with an increased risk for ACL injury.

Hypothesis

At foot contact during a sidestep cutting task, subjects use different movement strategies for shoe-surface conditions with a high coefficient of friction (COF) relative to a low friction condition. Specifically, the study tested for significant differences in knee kinematics, external knee moments, and the position of the center of mass for different COFs.

Study Design

Controlled laboratory study.

Methods

Twenty-two healthy subjects (11 male) were evaluated performing a 30° sidestep cutting task on a low friction surface (0.38) and a high friction surface (0.87) at a constant speed. An 8-camera markerless motion capture system combined with 2 force plates was used to measure full-body kinematics, kinetics, and center of mass.

Results

At foot contact, subjects had a lower knee flexion angle (P = .01), lower external knee flexion moment (P < .001), higher external knee valgus moment (P < .001), and greater medial distance of the center of mass from the support limb (P < .001) on the high friction surface relative to the low friction surface.

Conclusion

The high COF shoe-surface condition was associated with biomechanical conditions that can increase the risk of ACL injury. The higher incidence of ACL injury observed on high friction surfaces could be a result of these biomechanical changes. The differences in the biomechanical variables were the result of an anticipated stimulus due to different surface friction, with other conditions remaining constant.

Clinical Relevance

The risk analysis of ACL injury should consider the biomechanical movement changes that occur for a shoe-surface condition with high friction.
Early versus Late Start of Isokinetic Hamstring-Strengthening Exercise after Anterior Cruciate Ligament Reconstruction with Patellar Tendon Graft
Authors: Sekir Ufuk , Gur Hakan , Akova Bedrettin
Published: March 2010

Backgound

Hamstring strengthening after anterior cruciate ligament reconstruction is a vital component of the rehabilitation program.

Purpose

The objective of this trial was to investigate the effects of hamstring isokinetic training used in the early phase of the rehabilitation program on the stability, strength, symptoms, and functional outcomes of patients throughout 12 months after anterior cruciate ligament surgery.

Study Design

Randomized controlled clinical trial; Level of evidence, 2.

Methods

Forty-eight men underwent anterior cruciate ligament reconstruction with an ipsilateral bone—patellar tendon—bone autograft. The patients were randomly assigned to perform daily isokinetic hamstring exercises at postoperative 3 weeks (group I) or to perform daily isokinetic hamstring exercises at postoperative 9 weeks (group II). The patients were evaluated monthly for the first 4 months and at the 12th month for postoperative hamstring and quadriceps strength, as well as for knee function via the Cincinnati Knee Rating Scale and International Knee Documentation Committee form.

Results

Hamstring isometric strength at 30° of knee flexion (at the first and second months) and concentric isokinetic strength (at 2, 3, 4, and 12 months) at the angular velocity of 60 deg/s were significantly (P < .05-.01) greater in group I compared with group II. Average scores of the Cincinnati Knee Rating Scale for symptoms were significantly (P < .05-.001) higher in group I compared with group II at all evaluation periods. Walking and stair-climbing scores at 1, 2, 3, and 4 months and squatting score at all evaluation periods were also better (P < .05-.01) in group I compared with group II. In addition, group I exhibited better (P < .01-.001) Lachman test results compared with group II for all postoperative evaluation periods. The International Knee Documentation Committee final rating scores were significantly (P < .01) greater at 2, 3, and 4 months in group I compared with group II.

Conclusion

The results of this study suggest that hamstring as well as quadriceps strength can be increased via early hamstring strengthening after anterior cruciate ligament reconstruction with no negative impact on knee function.
Motion Control Shoe Delays Fatigue of Shank Muscles in Runners with Overpronating Feet
Authors: Cheung Roy T. H. , Ng Gabriel Y. F.
Published: March 2010

Background

The motion control shoe is a well-developed technology in running shoe design for controlling excessive rearfoot pronation and plantar force distribution. However, there is little information on the leg muscle activation with different shoe conditions.

Hypothesis

The motion control shoe can prevent excessive shank muscle activation and delay fatigue.

Study Design

Controlled laboratory study.

Methods

Twenty female recreational runners with excessive rearfoot pronation were tested with running 10 km on a treadmill on 2 days. Participants wore either a motion control running shoe or neutral running shoe on each day. Activities of their right tibialis anterior and peroneus longus were recorded with surface electromyography. The normalized root-mean-square electromyography and median frequency were compared between the 2 shoe conditions.

Results

Significant positive correlations were found between the root-mean-square eletromyography and running mileage in both the tibialis anterior and peroneus longus in the neutral shoe condition (P < .001). The median frequency dropped in both shoe conditions with mileage, but paired t tests revealed a significantly larger drop in the neutral shoe (P < .001 for peroneus longus, P = .074 for tibialis anterior).

Conclusion

The motion control shoe may facilitate a more stable activation pattern and higher fatigue resistance of the tibialis anterior and peroneus longus in individuals with excessive rearfoot pronation during running.

Clinical Relevance

The motion control shoe may increase the running endurance, thus reduce overuse injuries, in athletes with unstable feet during long-distance running.
Beyond Expulsion
Authors: Gerlach David
Published: March 2010

This article examines how the complexities of the Sudeten German expulsion and resettlement of the former Sudetenland spawned the notion that certain groups of people were unreliable or suspicious and, therefore, unwanted inhabitants. The intolerance and suspicion that setters, local and central officials, and others voiced toward different groups and actions directly related to the expulsion of Germans. The rapid influx of new settlers in search of German property and social mobility had a destabilizing effect on the region as well. The category of unwanted elements changed over time and reflected not necessarily the arrival of particular people but the problems unleashed by expulsion and settlement. The emergence of this category demonstrates how ethnic cleansing affected not only the targeted ethnic group but also how that process transformed people and places. This article offers new insights into the increasing body of literature on this topic in Central and Eastern European history by expanding the focus beyond Czechs and Germans. By examining a range of different sources, it also demonstrates that local actors as much as central ones created and sustained repressive attitudes in the borderlands.
Performance and haematological indices in rats exposed to monocrotophos contamination
Authors: Sunmonu TO , Oloyede OB
Published: March 2010

Monocrotophos is an organophosphate pesticide used in agriculture to control insect pests. Changes in performance and haematological parameters (such as packed cell volume, white blood cells, neutrophils, eosinophils and lymphocytes) were used to assess the effect of the pesticide on rats chronically exposed to 12.5 parts per million (ppm), 25 ppm, 50 ppm, 100 ppm and 200 ppm for 10 days, while the control rats were placed on borehole water. Administration of the pesticide to the animals resulted in several physical deteriorations including appearance and agility. A significant reduction (p < .05) was observed in the weight gained by rats while the liver-to-body weight ratio increased significantly (p < .05) as the level of exposure to monocrotophos increased. Whereas packed cell volume, white blood cells and lymphocytes increased significantly (p < .05), neutrophils and eosinophils counts reduced significantly (p < .05) as the concentration of monocrotophos in the drinking water increased. Overall, the data indicated that exposure to monocrotophos portends serious consequences on the performance and haematological parameters of rats.
Assessing Aggression Using Conditional Reasoning
Authors: James Lawrence R. , LeBreton James M.
Published: March 2010

In a time characterized by wars, students and employees being shot at their desks, and corporate executives raiding pension funds, aggression has taken on considerable prominence in our society. Aggressive people capture our interest because they are the ones who desire to harm others. Considerable progress has been made in recent years in understanding the aggressive personality. Psychology now has a much better idea of the defensive cognitive processes that aggressive people use to create a false sense of rationality for their aggressive acts. This knowledge of defensive processes was used to design a new measurement system to identify aggressive individuals. The new measurement system is based on a “cover” task in the form of an inductive reasoning problem. The use of reasoning to cover the measurement of aggression is made possible because aggressive people use the illusion of rational analyses to create defenses for their harming of others. The measurement system builds on this process by constructing answers to inductive reasoning problems that are grounded in the same defensive, self-illusionary thinking that aggressive people use to rationalize harming others. Aggressive people tend to be drawn to these answers (the answers in the previous sentence). This is because people who habitually engage in creating falsely rational defenses find reasoning based on the same types of protective thinking to be logically compelling.
More Than Happy
Authors: Sauter Disa
Published: March 2010

Despite great advances in scientific understanding of emotional processes in the last decades, research into the communication of emotions has been constrained by a strong bias toward negative affective states. Typically, studies distinguish between different negative emotions, such as disgust, sadness, anger, and fear. In contrast, most research uses only one category of positive affect, “happiness,” which is assumed to encompass all positive emotional states. This article reviews recent research showing that a number of positive affective states have discrete, recognizable signals. An increased focus on cues other than facial expressions is necessary to understand these positive states and how they are communicated; vocalizations, touch, and postural information offer promising avenues for investigating signals of positive affect. A full scientific understanding of the functions, signals, and mechanisms of emotions requires abandoning the unitary concept of happiness and instead disentangling positive emotions.
Energy Harvesting Devices Using Macro-fiber Composite Materials
Authors: Hyun Jeong Song  , Choi Young-Tai , Wereley Norman M. , Purekar Ashish S.
Published: March 2010

This study addresses the experimental validation of a design methodology for an energy harvesting device utilizing macro-fiber composite (MFC) materials. The energy harvesting device is composed of a cantilever beam with MFC elements, a tip mass, a rectifier, and an electrical resistance. A theoretical model of the energy harvesting device was developed for the estimation of generated power, voltage, and current under sinusoidal base excitation at its first natural frequency, and its performance verified via experiment. A parametric study was performed to gain insight into methods to maximize generated power and current based on perturbations to beam thickness, length, width, and density. Performance characteristics of the energy harvesting device utilizing two types of MFC patches (d31- and d33-types) were experimentally evaluated under different acceleration levels. In addition, the effects of beam thickness, natural frequency, and electrical resistance were experimentally investigated.
‘Flooding’ of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma
Authors: Keizer Ron J , Beijnen Jos H , Baas Paul
Published: March 2010

In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of ‘drowning’. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.
The language of anger in Chinese and English narratives
Authors: Woon Yee Ho Judy
Published: March 2010

This article analyses the language of anger used by the bilinguals in Hong Kong, and examines how the functions of L1 and L2 and users’ language proficiency may affect emotional expression. Thirty-three university students in Hong Kong participated in the research. Each was asked to write two stories about ‘an experience in which you were made angry’ and ‘an experience in which you made someone angry’, one in Chinese and the other in English. A total of 66 narrative texts were collected. The subjects also provided written comments on their feelings and language preferences in writing life stories. The narrative length, lexical and syntactic richness, and the use of metaphorical expressions in the Chinese and English texts were compared and triangulated with the subjects’ perceptions of bilinguality and emotionality. Both the linguistic data and the written comments suggest that to a very large extent language competence affects how emotionally expressive bilinguals can be. The ability to communicate and share one’s emotions is an integral part of one’s personal life but the language of emotions seems to be an under-developed area in second language education programmes. Measures are suggested to address this problem and help bilinguals to develop their competence in emotional expression.
Language alternation and choice in a formal register: Spanish and English in bilingual Catholic services
Authors: Alfaraz Gabriela G.
Published: March 2010

Language alternation tends to be proscribed in formal speech situations and registers; in bilingual communities, however, the use of two languages may be observed in formal speech events and registers. This article investigates the use of Spanish and English in a formal speech event, the religious ceremony performed in the Catholic mass, which is governed by prescribed rules of linguistic conduct, in order to examine the factors that constrain language alternation and choice. A quantitative analysis of six 60-minute services was used to determine the frequency of the two languages, both overall and in ritual versus non-ritual talk, and establish an empirical basis for describing the markedness of the two languages (Myers-Scotton, 2000, 2002). Patterns of language alternation are examined both at the macro level of the mass, from section to section, and at the micro level, within sections, and languages choices are explained using the Rational Choice model described by Myers-Scotton and Bolonyai (2001).
Examination of HA230 turbine transition duct
Authors: Veverková J. , Atkinson H. V. , Strang A. , Marchant G. R.
Published: March 2010

The present paper reports the results of an examination of a service run transition duct from one of Siemens’ industrial gas turbines and the correlation between the findings for this, and those from the studies undertaken on laboratory exposed Haynes alloy 230 material. The studies have shown that there are changes in the microstructure and hardness of the material that can be related to temperature and time of exposure, and the information gained can lead to estimations of the average component operating temperature. Metallographic studies revealed a high level of heterogeneity of the grains in this transition duct.
Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity
Authors: Mössner Ekkehard , Brünker Peter , Moser Samuel , Püntener Ursula , Schmidt Carla , Herter Sylvia , Grau Roger , Gerdes Christian , Nopora Adam , van Puijenbroek Erwin , Ferrara Claudia , Sondermann Peter , Jäger Christiane , Strein Pamela , Fertig Georg , Friess Thomas , Schüll Christine , Bauer Sabine , Dal Porto Joseph , Del Nagro Christopher , Dabbagh Karim , Dyer Martin J. S. , Poppema Sibrand , Klein Christian , Umaña Pablo
Published: March 2010

CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell–depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders.
The AF4·MLL fusion protein is capable of inducing ALL in mice without requirement of MLL·AF4
Authors: Bursen Adelheid , Schwabe Karen , Rüster Brigitte , Henschler Reinhard , Ruthardt Martin , Dingermann Theo , Marschalek Rolf
Published: March 2010

The chromosomal translocation t(4;11)(q21;q23) is the most frequent genetic aberration of the human MLL gene, resulting in high-risk acute lymphoblastic leukemia (ALL). To elucidate the leukemogenic potential of the fusion proteins MLL·AF4 and AF4·MLL, Lin−/Sca1+ purified cells (LSPCs) were retrovirally transduced with either both fusion genes or with MLL·AF4 or AF4·MLL alone. Recipients of AF4·MLL- or double-transduced LSPCs developed pro-B ALL, B/T biphenotypic acute leukemia, or mixed lineage leukemia. Transplantation of MLL·AF4- or mock-transduced LSPCs did not result in disease development during an observation period of 13 months. These findings indicate that the expression of the AF4·MLL fusion protein is capable of inducing acute lymphoblastic leukemia even in the absence of the MLL·AF4 fusion protein. In view of recent findings, these results may imply that t(4;11) leukemia is based on 2 oncoproteins, providing an explanation for the very early onset of disease in humans.
Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis
Authors: Huls Gerwin , Mulder André B. , Rosati Stefano , van de Loosdrecht Arjan A. , Vellenga Edo , de Wolf Joost T. M.
Published: March 2010

Patients with refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) are difficult to treat because the cytoreductive treatment might be beneficial for the thrombocytosis component but harmful for the RARS component. As lenalidomide has shown to be efficacious in both myelodysplastic syndromes and myeloproliferative neoplasms, we have treated 2 RARS-T patients, who were transfusion dependent, with lenalidomide. We report the results of lenalidomide treatment in these patients and show that lenalidomide has clinical activity in this rare disorder. Both patients became transfusion independent, and 1 of the patients attained indeed a complete molecular remission.
A 47-year-old female with shortness of breath and “reversed halo sign”
Authors: Maimon N.
Published: March 2010

A 47-yr-old female was referred to a tertiary centre for further evaluation of chronic cough, fever, progressive exertional dyspnoea and fatigue. From a respiratory point of view she had been well until 7 months previously when she had started to experience systemic fatigue, low-grade fever and chronic dry cough. A computed tomography scan of the chest demonstrated diffuse bilateral ground-glass, ill-defined pulmonary opacities affecting all lobes. Some had central ground-glass hazy density with peripheral areas of increased opacity, which is consistent with “reversed halo sign”.

Cryptogenic organising pneumonia (COP) is a clinical, radiological and pathological diagnosis which is made when no definite cause, such as infection or connective tissue disease, is found. It is characterised histopathologically by the presence of patchy distribution of granulation tissue, which consists of fibroblasts and myofibroblasts embedded in a loose connective matrix, present in the lumen of the distal airspaces including alveoli, alveolar ducts and bronchioles.

This case report illustrates the association of the reversed halo sign with COP. Although only seen in one fifth of patients with the disease, it appears to suggest the diagnosis of COP and, with proper clinical correlation, it may be another diagnostic adjunct.
Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology
Authors: Humbert M.
Published: March 2010

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker.

The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH.

However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy.
Exercise training and pulmonary rehabilitation: new insights and remaining challenges
Authors: Troosters T. , Gosselink R. , Janssens W. , Decramer M.
Published: March 2010

Pulmonary rehabilitation is now regarded as an evidence-based treatment for symptomatic patients with chronic obstructive pulmonary disease. It has been shown to enhance exercise tolerance, improve symptoms and health-related quality of life, and reduce exacerbations in patients with recurrent exacerbations. In this article we review the mechanisms through which exercise training results in beneficial effects. We also review three challenges that currently remain: 1) the fine tuning of exercise training and multidisciplinary programmes; 2) the timing of rehabilitation; and 3) efforts to enhance the accessibility and adherence to pulmonary rehabilitation programmes. Further research is needed in order to apply the now well-established principles of pulmonary rehabilitation to unusual patient populations, or patient populations that are unlikely to participate in conventional outpatient programmes.
Altered expression of microRNAs in the myocardium of rats with acute myocardial infarction
Authors: Shi Bing , Guo Yanhong , Wang Juan , Gao Wei
Published: March 2010

Background

MicroRNAs(miRNAs) are important cellular components and their dysfunction is associated with various diseases. Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases. Although several miRNAs are reported to be associated with AMI, more novel miRNAs are needed to further investigate and improve certainty

Methods

We applied a well-established acute myocardial infarction rat model and performed miRNAs microarray experiments upon the myocardium tissue of rats with AMI and under sham control. We identified the differentially expressed miRNAs and analyzed the function of miRNA targets, transcription factors, and host genes based on bioinformatics.

Results

As a result, the levels of expression of seventeen miRNAs significantly deregulated, of which four miRNAs were further validated by qRT-PCR. In addition, we observed that the transcription factors, targets, and host genes of these deregulated miRNAs are enriched in cardiovascular-related functions.

Conclusion

We found that the miRNAs expression level altered in rats with AMI and differentially expressed miRNAs may be novel biomarkers of AMI.
Gene expression profiles of lung adenocarcinoma linked to histopathological grading and survival but not to EGF-R status: a microarray study
Authors: Neumann Jens , Feuerhake Friedrich , Kayser Gian , Wiech Thorsten , Aumann Konrad , Passlick Bernward , Fisch Paul , Werner Martin , zur Hausen Axel
Published: March 2010

Background

Several different gene expression signatures have been proposed to predict response to therapy and clinical outcome in lung adenocarcinoma. Herein, we investigate if elements of published gene sets can be reproduced in a small dataset, and how gene expression profiles based on limited sample size relate to clinical parameters including histopathological grade and EGFR protein expression.

Methods

Affymetrix Human Genome U133A platform was used to obtain gene expression profiles of 28 pathologically and clinically annotated adenocarcinomas of the lung. EGFR status was determined by fluorescent in situ hybridization and immunohistochemistry.

Results

Using unsupervised clustering algorithms, the predominant gene expression signatures correlated with the histopathological grade but not with EGFR protein expression as detected by immunohistochemistry. In a supervised analysis, the signature of high grade tumors but not of EGFR overexpressing cases showed significant enrichment of gene sets reflecting MAPK activation and other potential signaling cascades downstream of EGFR. Out of four different previously published gene sets that had been linked to prognosis, three showed enrichment in the gene expression signature associated with favorable prognosis.

Conclusions

In this dataset, histopathological tumor grades but not EGFR status were associated with dominant gene expression signatures and gene set enrichment reflecting oncogenic pathway activation, suggesting that high immunohistochemistry EGFR scores may not necessarily be linked to downstream effects that cause major changes in gene expression patterns. Published gene sets showed association with patient survival; however, the small sample size of this study limited the options for a comprehensive validation of previously reported prognostic gene expression signatures.
Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells
Authors: Bryant Christopher S , Kumar Sanjeev , Chamala Sreedhar , Shah Jay , Pal Jagannath , Haider Mahdi , Seward Shelly , Qazi Aamer M , Morris Robert , Semaan Assaad , Shammas Masood A , Steffes Christopher , Potti Ravindra B , Prasad Madhu , Weaver Donald W , Batchu Ramesh B
Published: March 2010

Background

Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

Results

SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.

Conclusions

SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.
Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review
Authors: Kuhlmann Inga , Minihane Anne Marie , Huebbe Patricia , Nebel Almut , Rimbach Gerald
Published: March 2010

Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex.

ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.
Predicting progression of Alzheimer's disease
Authors: Doody Rachelle S , Pavlik Valory , Massman Paul , Rountree Susan , Darby Eveleen , Chan Wenyaw
Published: March 2010

Introduction

Clinicians need to predict prognosis of Alzheimer's disease (AD), and researchers need models of progression to develop biomarkers and clinical trials designs. We tested a calculated initial progression rate to see whether it predicted performance on cognition, function and behavior over time, and to see whether it predicted survival.

Methods

We used standardized approaches to assess baseline characteristics and to estimate disease duration, and calculated the initial (pre-progression) rate in 597 AD patients followed for up to 15 years. We designated slow, intermediate and rapidly progressing groups. Using mixed effects regression analysis, we examined the predictive value of a pre-progression group for longitudinal performance on standardized measures. We used Cox survival analysis to compare survival time by progression group.

Results

Patients in the slow and intermediate groups maintained better performance on the cognitive (ADAScog and VSAT), global (CDR-SB) and complex activities of daily living measures (IADL) (P values < 0.001 slow versus fast; P values < 0.003 to 0.03 intermediate versus fast). Interaction terms indicated that slopes of ADAScog and PSMS change for the slow group were smaller than for the fast group, and that rates of change on the ADAScog were also slower for the intermediate group, but that CDR-SB rates increased in this group relative to the fast group. Slow progressors survived longer than fast progressors (P = 0.024).

Conclusions

A simple, calculated progression rate at the initial visit gives reliable information regarding performance over time on cognition, global performance and activities of daily living. The slowest progression group also survives longer. This baseline measure should be considered in the design of long duration Alzheimer's disease clinical trials.
Different but Equal? How Nonmajors and Majors Approach and Learn Genetics
Authors: Knight Jennifer K. , Smith Michelle K.
Published: March 2010

Introductory biology courses are frequently offered separately to biology majors and nonbiology majors, with the assumption that the two groups of students are different enough to merit different courses. To assess the evidence behind this assumption, we compared students in two different genetics classes at the University of Colorado–Boulder, one class for nonscience majors (nonmajors) and the other class for biology majors and students planning a biology-related career (majors), to see whether these two groups of students were fundamentally different in performance and attitudes. To measure content knowledge, we administered identical assessments to both groups of students during the semester: a validated pre- and postcontent assessment (Genetics Concept Assessment), ungraded quizzes after problem-solving sessions, and questions on each exam. We measured attitudes, study time, and study techniques through online surveys. Majors outperformed nonmajors on content assessments, finishing with significantly higher learning gains. Nonmajors and majors also differed in their motivation, interest, study time, and expert-level of beliefs. We suggest that focusing on the process of science and its connection to students' lives will better engage and motivate nonmajors while still helping them learn the fundamental concepts of genetics.
Maritza Macdonald
Authors: Mays Hoopes Laura L.
Published: March 2010

Note from the Editor

Educator Highlights for CBE—Life Sciences Education show how professors at different kinds of institutions educate students in life sciences with inspiration and panache. If you have a particularly creative teaching portfolio yourself, or if you wish to nominate an inspiring colleague to be profiled, please e-mail Laura Hoopes at lhoopes@pomona.edu .
Editorial: T cells, not “immune” from HIF
Authors: Melillo Giovanni
Published: March 2010

Commentary on the article by Naldini et al. and new data on hypoxic T cells, HIF, and angiogenesis.
Attention-deficit hyperactivity disorder in adults
Authors: Janakiraman Raguraman , Benning Tony
Published: March 2010

Attention-deficit hyperactivity disorder (ADHD) is an established diagnosis in children but there is a lack of agreement about its validity as a distinct entity in adults. Literature suggests that between one-third and two-thirds of children diagnosed with ADHD continue to manifest symptoms into adulthood. An adult diagnosis should be done on the basis of a thorough assessment, structured and semi-structured clinical interview, and with a complete understanding of the symptoms that manifest in adults. This may be supplemented by the use of rating scales. We present a review of the literature covering aetiology, clinical presentations, diagnostic evaluation and management of ADHD in adults.
Mentally disordered detainees in the police station: the role of the psychiatrist
Authors: Kent John , Gunasekaran Santhana
Published: March 2010

A significant number of people who come into contact with the police have a mental disorder. Attending the police station to assess detainees forms a significant part of most psychiatrists' work. The role of the psychiatrist includes assessing for the presence of mental disorder, advising on diversion from custody and assessing detainees' fitness to be interviewed. This article, based on data primarily from the UK, looks at issues involved for psychiatrists attending police stations, including pathways to care, epidemiology, assessment of detainees under the Mental Health Act 1983, fitness of detainees to be interviewed and aspects of training.
Resolution and remission in schizophrenia: getting well and staying well
Authors: Yeomans David , Taylor Mark , Currie Alan , Whale Richard , Ford Keith , Fear Chris , Hynes Joanne , Sullivan Gary , Moore Bruce , Burns Tom
Published: March 2010

Remission is a new research outcome indicating long-term wellness. Remission not only sets a standard for minimal severity of symptoms and signs (resolution); it also sets a standard for how long symptoms and signs need to remain at this minimal level (6 months). Individuals who achieve remission from schizophrenia have better subjective well-being and better functional outcomes than those who do not. Research suggests that remission can be achieved in 20–60% of people with schizophrenia. There is some evidence of the usefulness of remission as an outcome indicator for clinicians, service users and their carers. This article reviews the literature on remission in schizophrenia and asks whether it could be a useful clinical standard of well-being and a foundation for functional improvement and recovery.
Partner alcohol use, violence and women's mental health: population-based survey in India
Authors: Nayak Madhabika B. , Patel Vikram , Bond Jason C. , Greenfield Thomas K.
Published: March 2010

Background

The relationship between partner alcohol use and violence as risk factors for poor mental health in women is unclear.

Aims

To describe partner-related and other psychosocial risk factors for common mental disorders in women and examine interrelationships between these factors.

Method

Data are reported on 821 women aged 18–49 years from a larger population study in north Goa, India. Logistic regression models evaluated the risks for women's common mental disorders and tested for mediation effects in the relationship between partner alcohol use and these disorders.

Results

Excessive partner alcohol use increased the risk for common mental disorders two- to threefold. Partner violence and alcohol-related problems each partially mediated the association between partner excessive alcohol use and these mental disorders. Women's own violence-related attitudes were also independently associated with them.

Conclusions

Partner alcohol use, partner violence and women's violence-related attitudes must be addressed to prevent and treat common mental disorders in women.
Patients' views of involuntary hospital admission after 1 and 3
months: prospective study in 11 European countries
Authors: Priebe Stefan , Katsakou Christina , Glöckner Matthias , Dembinskas Algirdas , Fiorillo Andrea , Karastergiou Anastasia , Kiejna Andrzej , Kjellin Lars , Nawka Pìtr , Onchev George , Raboch Jiri , Schuetzwohl Matthias , Solomon Zahava , Torres-González Francisco , Wang Duolao , Kallert Thomas
Published: March 2010

Background

Legislation and practice of involuntary hospital admission vary
substantially among European countries, but differences in outcomes have
not been studied.

Aims

To explore patients' views following involuntary hospitalisation in
different European countries.

Method

In a prospective study in 11 countries, 2326 consecutive involuntary
patients admitted to psychiatric hospital departments were interviewed
within 1 week of admission; 1809 were followed up 1 month and 1613 3
months later. Patients' views as to whether the admission was right were
the outcome criterion.

Results

In the different countries, between 39 and 71% felt the admission was
right after 1 month, and between 46 and 86% after 3 months. Females,
those living alone and those with a diagnosis of schizophrenia had more
negative views. Adjusting for confounding factors, differences between
countries were significant.

Conclusions

International differences in legislation and practice may be relevant to
outcomes and inform improvements in policies, particularly in countries
with poorer outcomes.
‘I want to be bipolar’…a new phenomenon
Authors: Chan Diana , Sireling Lester
Published: March 2010

There has been renewed interest in the concept and diagnosis of bipolar affective disorder in recent years. Previous epidemiological studies have reported the prevalence of the disorder in the USA at 1–2% but further studies have shown that the disorder is underdiagnosed and the true prevalence may be as high as 11%. Despite the stigma attached to mental illness, we have noticed in our clinical practice a new and unusual phenomenon, where patients present to psychiatrists with self-diagnosed bipolar disorder. Here, we explore the background to this phenomenon, the diagnostic challenges and the implications for our patients and practice.
Long-term follow-up of individuals on assertive outreach teams
Authors: Rana Tanvir , Commander Martin
Published: March 2010

Aims and method

To describe the long-term outcome of 165 people taken onto assertive outreach teams.

Results

After a mean follow-up of 6 years and 8 months, 130 people remained in contact with local services of whom 100 were still under the care of an assertive outreach team. Admission rates remained around half those at inception. However, 16 individuals had died, 10 spent time in prison, 12 were homeless and 14 had protracted stays in hospital during the follow-up period.

Clinical implications

Although assertive outreach teams are successful in engaging individuals and reducing admission rates, these benefits plateau after the first few years and could possibly be sustained by other services that may in addition focus more on those areas where teams have proven less effective including physical health, housing and employment.
Comparable Survival Between pN0 Breast Cancer Patients Undergoing Sentinel Node Biopsy and Extensive Axillary Dissection: A Report From the Korean Breast Cancer Society
Authors: Moon Hyeong-Gon , Han Wonshik , Noh Dong-Young
Published: March 2010

Purpose

Recent studies showing survival benefit of extensive axillary lymph node dissection (ALND) in pN0 breast cancer have challenged the concept of sentinel node biopsy (SNB). In this study, the survival and recurrence after SNB alone and ALND in pN0 Korean breast cancer patients were investigated.

Patients and Methods

Using information from two large databases, including a Korean nationwide registry, we assessed survival relative to the extent of ALND in pN0 breast cancer patients. We also compared the survival of pN0 patients who underwent SNB alone with survival in those who underwent varying degrees of ALND.

Results

In an analysis of 1,607 pN0 patients from a single institution, less extensive ALND significantly increased the risks of breast cancer death and systemic recurrence but not of locoregional recurrence. These findings were validated by an analysis of nationwide registry data on 17,672 pN0 patients; patients with > 20 dissected lymph nodes had significantly better overall survival (OS) and breast cancer–specific survival (BCSS) than those with 10 to 20 or < 10 dissected lymph nodes. Patients who underwent SNB alone showed OS (hazard ratio [HR], 1.03; 9% CI, 0.08 to 1.56) and BCSS (HR, 1.15; 95% CI, 0.75 to 1.78) similar to those of patients who underwent extensive ALND (> 20 dissected lymph nodes), despite the small number of lymph nodes removed.

Conclusion

Extensive ALND is associated with better survival and less systemic recurrence than less extensive ALND in patients with pN0 breast cancer. However, SNB alone showed excellent survival results, similar to those of extensive ALND, supporting the long-term oncologic safety of SNB.