bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Engineering
Authors: VanderSteen Jonathan
Published: February 2011

Engineers today cannot meet their professional obligation to the welfare of society if they do not have a broad, multidisciplinary vision, and yet a multidisciplinary vision is becoming enormously difficult to obtain. A new curriculum must emerge that can integrate a focused, discipline-based scientific approach with an integrated approach. To do this, we must recognize that there is already a structure that is deeply embedded into the current pedagogy, which values performance ratios such as efficiency as paramount. Current trends indicate a call for a broader, reflexive, and preventative curriculum, but like many other calls for change, these will fail if the focus continues to be on wrong values. A model for an adaptive engineering curriculum is developed that strives to maintain a scientific approach as well as a broad “culture-based approach.” A new way of thinking about engineering curriculum must involve a “resymbolization” in which experience, context, community, and certain nonmeasurable principles are valued.
Sensitivity and Specificity of Subacute Computerized Neurocognitive Testing and Symptom Evaluation in Predicting Outcomes After Sports-Related Concussion
Authors: Lau Brian C. , Collins Michael W. , Lovell Mark R.
Published: February 2011

Background: Concussions affect an estimated 136 000 high school athletes yearly. Computerized neurocognitive testing has been shown to be appropriately sensitive and specific in diagnosing concussions, but no studies have assessed its utility to predict length of recovery. Determining prognosis during subacute recovery after sports concussion will help clinicians more confidently address return-to-play and academic decisions.

Purpose: To quantify the prognostic ability of computerized neurocognitive testing in combination with symptoms during the subacute recovery phase from sports-related concussion.

Study Design: Cohort study (prognosis); Level of evidence, 2.

Methods: In sum, 108 male high school football athletes completed a computer-based neurocognitive test battery within 2.23 days of injury and were followed until returned to play as set by international guidelines. Athletes were grouped into protracted recovery (>14 days; n = 50) or short-recovery (≤14 days; n = 58). Separate discriminant function analyses were performed using total symptom score on Post-Concussion Symptom Scale, symptom clusters (migraine, cognitive, sleep, neuropsychiatric), and Immediate Postconcussion Assessment and Cognitive Testing neurocognitive scores (verbal memory, visual memory, reaction time, processing speed).

Results: Multiple discriminant function analyses revealed that the combination of 4 symptom clusters and 4 neurocognitive composite scores had the highest sensitivity (65.22%), specificity (80.36%), positive predictive value (73.17%), and negative predictive value (73.80%) in predicting protracted recovery. Discriminant function analyses of total symptoms on the Post-Concussion Symptom Scale alone had a sensitivity of 40.81%; specificity, 79.31%; positive predictive value, 62.50%; and negative predictive value, 61.33%. The 4 symptom clusters alone discriminant function analyses had a sensitivity of 46.94%; specificity, 77.20%; positive predictive value, 63.90%; and negative predictive value, 62.86%. Discriminant function analyses of the 4 computerized neurocognitive scores alone had a sensitivity of 53.20%; specificity, 75.44%; positive predictive value, 64.10%; and negative predictive value, 66.15%.

Conclusion: The use of computerized neurocognitive testing in conjunction with symptom clusters results improves sensitivity, specificity, positive predictive value, and negative predictive value of predicting protracted recovery compared with each used alone. There is also a net increase in sensitivity of 24.41% when using neurocognitive testing and symptom clusters together compared with using total symptoms on Post-Concussion Symptom Scale alone.
No Effect of Extracorporeal Shockwave Therapy on Patellar Tendinopathy in Jumping Athletes During the Competitive Season
Authors: Zwerver Johannes , Hartgens Fred , Verhagen Evert , van der Worp Henk , van den Akker-Scheek Inge , Diercks Ron L.
Published: February 2011

Background: Patellar tendinopathy is a common overuse injury among jumping athletes. No evidence-based treatment guidelines exist. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment but its effectiveness has not been studied in athletes with patellar tendinopathy who have symptoms for 3 to 12 months and are still playing.

Purpose: The TOPGAME study was created to determine the effectiveness of ESWT on pain, symptoms, and function in athletes with early symptomatic patellar tendinopathy who are still in training and competition.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: Athletes playing volleyball, basketball, or handball with patellar tendinopathy for 3 to 12 months were randomized into the ESWT or placebo group during the first half of the season. The ESWT group received 3 ESWT treatments while the placebo group received sham ESWT. In-season follow-up measurements were 1, 12, and 22 weeks after treatment. The primary outcome was severity of patellar tendinopathy determined with the Victorian Institute of Sport Assessment–Patella (VISA-P) questionnaire. Secondary outcome measures were pain during activities of daily living and sports and after functional knee-loading tests rated on a visual analog scale and subjective improvement. Multilevel analyses were performed to determine differences between groups over time.

Results: Of the 127 symptomatic athletes invited to participate, 62 were eligible, gave consent, and were randomized into the ESWT (n = 31) or placebo group (n = 31). Mean VISA-P scores before and 1, 12, and 22 weeks after treatment were 59.4 (±11.7), 66.8 (±16.2), 66.7 (±17.5), and 70.5 (±18.9) for the ESWT group and 62.4 (±13.4), 66.3 (±19.0), 68.9 (±20.3), and 72.7 (±18.0) for the placebo group. For the VISA-P, there was a significant effect for time ( P < .01) but no treatment × time interaction effect ( P = .82). The same pattern was seen in visual analog scale pain scores. One week after final treatment, significantly more athletes in the ESWT group reported subjective improvement (65% vs 32%; χ2 = 6.46, P = .01). This was the only difference noted between the 2 groups.

Conclusion: Extracorporeal shockwave therapy as a solitary treatment during the competitive season has no benefit over placebo treatment in the management of actively competing jumping athletes with patellar tendinopathy who have symptoms for less than 12 months.
Examination of the Psychometric Properties of the Test Anxiety Scale for Elementary Students (TAS-E) Scores
Authors: Lowe Patricia A. , Grumbein Matthew J. , Raad Jennifer M.
Published: February 2011

The psychometric properties of the Test Anxiety Scale for Elementary Students (TAS-E) scores were examined. In Study 1, an exploratory factor analysis (EFA) was performed on the responses of 997 students in Grades 2 to 6 on the TAS-E. The results of the EFA produced a four-factor solution: Physiological Hyperarousal, Social Concerns, Task Irrelevant Behavior, and Worry. Gender differences were also found on each factor, except the Social Concerns factor. In Study 2, a confirmatory factor analysis (CFA) was performed on the TAS-E scores with a sample of 421 elementary students. The CFA results provided support for the four-factor solution in Study 1. The results also indicated that the TAS-E scores had adequate internal consistency reliability and test score stability. Evidence for convergent and discriminant validity of the TAS-E scores was found.
Prenatal Brain Disruption in Molybdenum Cofactor Deficiency
Authors: Carmi-Nawi Nirit , Malinger Gustavo , Mandel Hanna , Ichida Kimiyoshi , Lerman-Sagie Tally , Lev Dorit
Published: February 2011

Molybdenum cofactor deficiency is a rare autosomal recessive disorder that may present during the neonatal period with intractable seizures and be mistaken for ischemic encephalopathy. We describe a patient whose prenatal sonography at 35 weeks’ gestation revealed diffuse brain damage with multiple subcortical cavities, ventriculomegaly, dysgenesis of the corpus callosum, and a hypoplastic cerebellum with an enlarged cisterna magna. Magnetic resonance imaging (MRI) later revealed brain atrophy, and multicystic encephalomalacia with hypoplastic vermis and cerebellum. Neurological examination at 10 months showed microcephaly, profound mental retardation, and spasticity. Uric acid was low, and taurine and xanthine were increased in the urine. A sulfite test was positive. The diagnosis of molybdenum cofactor deficiency was made. Sulfite oxidase activity in fibroblasts was undetectable. The patient was found to be homozygous for the 251-418del in the MOCS1 gene. This is the first description of the prenatal development of severe brain disruption in molybdenum cofactor deficiency.
Carpal Tunnel Syndrome Secondary to Ganglion Cyst in a Child
Authors: Mohamed Ahmad , Rosalie Sarah , Taylor Kim , Fink Michelle , Coombs Christopher , Ryan Monique , Kornberg Andrew
Published: February 2011

Carpal tunnel syndrome is uncommon in children and is associated with an underlying etiology in the majority of cases. The diagnosis of the condition in childhood is dependent on a high degree of clinical suspicion, careful clinical examination, and judicious use of confirmatory investigations. The authors report a novel cause of carpal tunnel syndrome in a child, and discuss the investigation and management strategies in childhood carpal tunnel syndrome.
On Being and Calling Oneself a Feminist Social Worker
Authors: Valentich Mary
Published: February 2011

This article examines the nature of identity as a feminist social worker in an era when feminism is no longer the driving force for social work that it was from the 1970s to the 1990s. What does it mean to be a feminist practitioner in a period of conservatism? How can identity be fostered? What are the implications for social work education and practice? When social work students and social workers are mostly hesitant to call themselves feminist social workers, perhaps, it would be wiser to focus on the application of feminist principles. What is lost and what may be gained by giving up on identity and pursuing feminist principles in education, research, practice, and administration?
Managing in the Contemporary World
Authors: Muganyizi Projestine S. , Nyström Lennarth , Axemo Pia , Emmelin Maria
Published: February 2011

Grounded theory guided the analysis of 30 in-depth interviews with raped women and community members who had supported raped women in their contact with the police and health care services in Tanzania. The aim of this study was to understand and conceptualize the experiences of the informants by creating a theoretical model focusing on barriers, strategies, and responses during the help seeking process. The results illustrate a process of managing in the contemporary world characterized as walking a path of anger and humiliation. The barriers are illustrated by painful experiences of realizing it’s all about money, meeting unprofessionalism and irresponsibility, subjected to unreliable services, and by being caught in a messed-up system. Negotiating truths and knowing what to do capture the informants’ coping strategies. The study indicates an urgent need for improvement in the formal procedures of handling rape cases, improved collaboration between the police and the health care system, as well as specific training for professionals to improve their communication and caring skills.
Violation of ethical principles in institutional care for older people
Authors: Bužgová Radka , Ivanová Kateřina
Published: February 2011

This study focuses on issues of elder abuse in residential settings. Violation of ethical principles is shown in the results of this quantitative study aimed at defining the extent, nature and causes of such abuse by employees’ unethical conduct towards clients in senior homes (i.e. residential nursing homes) in the Moravian-Silesian region of the Czech Republic. The research sample comprised 454 employees and 488 clients from 12 residential homes for older people. The data were collected from interviews with clients, who also received a questionnaire concerning their satisfaction with the institution. Two questionnaires were administered to the employees, one based on a pilot qualitative study and a second to investigate burnout. Outcomes were assessed according to the extent and form of elder abuse, the causes of elder abuse and the violation of basic ethical principles. The responses, in particular those of employees, revealed both psychological and physical abuse of older clients, and thus violation of two basic principles: respect for the person and non-maleficence. The group at risk of elder abuse comprised aggressive and dissatisfied clients, as well as those with mental problems and dementia. The employees most at risk of being abusers were those who had been employed in institutional care for more than five years, had inadequate knowledge about social services and suffered from burnout. The prevention of elder abuse is recommended to be through education focused on ethical principles, increasing employees’ satisfaction by promoting a friendly and safe organizational culture, and providing adequate working conditions.
Clinical ethical conflicts of nurses and physicians
Authors: Gaudine Alice , LeFort Sandra M , Lamb Marianne , Thorne Linda
Published: February 2011

Much of the literature on clinical ethical conflict has been specific to a specialty area or a particular patient group, as well as to a single profession. This study identifies themes of hospital nurses’ and physicians’ clinical ethical conflicts that cut across the spectrum of clinical specialty areas, and compares the themes identified by nurses with those identified by physicians. We interviewed 34 clinical nurses, 10 nurse managers and 31 physicians working at four different Canadian hospitals as part of a larger study on clinical ethics committees and nurses’ and physicians’ use of these committees. We describe nine themes of clinical ethical conflict that were common to both hospital nurses and physicians, and three themes that were specific to physicians. Following this, we suggest reasons for differences in nurses’ and physicians’ ethical conflicts and discuss implications for practice and research.
Script proposals: A device for empowering clients in counselling
Authors: Emmison Michael , Butler Carly W. , Danby Susan
Published: February 2011

Much of the research on the delivery of advice by professionals such as physicians, health workers and counsellors, both on the telephone and in face-to-face interaction more generally, has focused on the theme of client resistance and the consequent need for professionals to adopt particular formats to assist in the uptake of the advice. In this article we consider one setting, Kid’s Helpline, the national Australian counselling service for children and young people, where there is an institutional mandate not to give explicit advice in accordance with the values of self-direction and empowerment. The article examines one practice, the use of script proposals by counsellors, which appears to offer a way of providing support which is consistent with these values. Script proposals entail the counsellors packaging their advice as something that the caller might say — at some future time — to a third party such as a friend, teacher, parent or partner, and involve the counsellor adopting the speaking position of the caller in what appears as a rehearsal of a forthcoming strip of interaction. Although the core feature of a script proposal is the counsellor’s use of direct reported speech, they appear to be delivered not so much as exact words to be followed, but as the type of conversation that the client needs to have with the third party. Script proposals, in short, provide models of what to say as well as alluding to how these could be emulated by the client. In their design, script proposals invariably incorporate one or more of the most common rhetorical formats for maximizing the persuasive force of an utterance such as a three-part list or a contrastive pair. Script proposals, moreover, stand in a complex relation to the prior talk and one of their functions appears to be to summarize, respecify or expand upon the client’s own ideas or suggestions for problem solving that have emerged in these preceding sequences.
Identifying interpersonal stance in threatening discourse: An appraisal analysis
Authors: Gales Tammy
Published: February 2011

Ideologies about threatening language from scholarly and practitioner communities of practice reflect a genre replete with stances of violence and threatener control, wherein authorial intent is more strongly attributed to threats possessing characteristics that strengthen a threatener’s role in or commitment to the act (e.g. commitment modals, certainty adverbs) (Gales, 2010). Using the resources of Appraisal analysis (Martin and White, 2005), this article examines the ways in which interpersonal stances, or a speaker or writer’s commitment to or attitudes about a person or proposition (Biber et al., 1999), are manifested and function in a realized threat of violence. The analysis reveals that threateners use myriad rhetorical strategies to convey interpersonal meaning (Martin and Rose, 2003) and take stances that both strengthen and weaken their apparent level of commitment, thus contradicting the one-sidedness of threatening language ideologies and demonstrating the need for further research on stancetaking in threatening discourse.
Mundane whistleblowing: Social drama in assessment talk
Authors: Tholander Michael
Published: February 2011

Based on recordings of naturalistic interaction, this study explores how a case of mundane whistleblowing unfolds in real time. In the analyzed recordings, a teacher instructs five students to engage in self- and peer-assessment. A few minutes into the session, one of the students indirectly accuses his peers of staging a cover-up. This whistleblowing action is analyzed in detail, but the main analytical focus is on the conversational strategies employed in response to it. These strategies — for example, emotional displays, the undermining of credibility, fabricated accusatory detailing, covert silencing, puzzle work, and threats — were used both to repair the potential damage of the whistleblowing and to punish the whistleblower. More overt and hostile strategies were used after the formal assessment was over and the teacher had left the students to themselves. Students’ participation in the studied type of activities can be seen to develop their capacity to transform social relationships, to broaden their notions of peer loyalty, and to enhance their sense of social structure.
On the value of political legitimacy
Authors: Coakley Mathew
Published: February 2011

Theories of political legitimacy normally stipulate certain conditions of legitimacy: the features a state must possess in order to be legitimate. Yet there is obviously a second question as to the value of legitimacy: the normative features a state has by virtue of it being legitimate (such as it being owed obedience, having a right to use coercion, or enjoying a general justification in the use of force). I argue that it is difficult to demonstrate that affording these to legitimate states is morally desirable, and that obvious alternative conceptions of the value of legitimacy (notably epistemic and instrumental) are not without problems of their own. The intuitive triviality of establishing the value of normative legitimacy may mask a serious problem.
Contract Length and Salaries Compensating Wage Differentials in Major League Baseball
Authors: Link Charles R. , Yosifov Martin
Published: February 2011

This study investigates the relationship between free agent salaries and contract length in Major League Baseball (MLB) to examine whether players trade-off returns to performance for additional job security. This study is the first to conduct a comprehensive, multiperiod study of salary determination for all MLB position players who were free agents and signed contracts between 1984-1994 and 2003-2006. The authors use the same technique and variables in all models so that comparisons across time are possible. The empirical results of this study indicate that free agent position players appear willing to trade monetary returns to performance for the security of a longer guaranteed contract. The results are not sensitive to the definition of salary used but are sensitive to the productivity measure employed. The results are least compelling for 1990-1994, a result that is different from the finding of Krautmann and Oppenheimer.
The Impact of Educational Reforms on the Work of the School Principal in the United Arab Emirates
Authors: Thorne Christine
Published: February 2011

Although much has been written about the complexity of educational change and reform elsewhere, the educational reform movement in the United Arab Emirates (UAE) is a relatively recent phenomenon with little systematic documentation as yet; educators are still searching for a clear understanding of their roles. However, it is clear that the leadership of the country is exerting great pressure for reform in schools and there is a sense of urgency about the need for large-scale change. This article examines the impact of these reforms on the work of one school principal at this time of radical transformation. It begins with a brief review of some of the specific changes taking place in the emirate of Abu Dhabi including the introduction of a public private partnership model in public schools and a brief discussion of the role of school principals in the management of change. This is followed by a description of the study and the methodological design underpinning it. The findings of the study are presented and discussed and the article concludes with some recommendations for further research.
A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD
Authors: Sasaki Takahiko , Nakayama Katsutoshi , Yasuda Hiroyasu , Yamaya Mutsuo
Published: February 2011

Acute exacerbations of chronic obstructive pulmonary disease (COPD), an acute worsening of respiratory symptoms, generally result in a poor prognosis. Successful prevention and management of such exacerbations is thus important for patient care. Viral infection, primarily with rhinovirus (RV), is the foremost cause of exacerbations in COPD patients. Proton pump inhibitors (PPIs) have been reported to inhibit RV infection in human airway epithelial cells in vitro. Furthermore, clinical trials of PPIs in patients with COPD resulted in a reduction in rates of both common cold and COPD exacerbations. In this review, we discuss the significance of COPD exacerbations, summarize a published trial of the effect of low-dose PPIs on COPD exacerbations, and postulate a mechanism for this effect.
In vitro requirement for periostin in B lymphopoiesis
Authors: Siewe Basile T. , Kalis Susan L. , Le Phong T. , Witte Pamela L. , Choi Sangdun , Conway Simon J. , Druschitz Laurel , Knight Katherine L.
Published: February 2011

B lymphopoiesis arrests in rabbits by 4 months of age. To identify molecules that contribute to this arrest, cDNA–representational difference analysis on BM stromal cells from young and adult rabbits showed that expression of Postn that encodes for the extracellular matrix protein periostin dramatically reduced with age. Postn–small interfering RNA OP9 cells lost their capacity to support B-cell development from rabbit or murine BM cells, and reexpression of periostin restored this potential, indicating an in vitro requirement for periostin in B lymphopoiesis. In our system, we determined that periostin deficiency leads to increased cell death and decreased proliferation of B-lineage progenitors. Further, RGD peptide inhibition of periostin/αvβ3 interaction resulted in a marked decrease in B lymphopoiesis in vitro. Microarray analysis of the Postn–small interfering RNA OP9 cells showed decreased expression of key B-lymphopoietic factors, including IL-7 and CXCL12. In vivo, unidentified molecule(s) probably compensate periostin loss because Postn−/− mice had normal numbers of B-cell progenitors in BM. We conclude that the decline in periostin expression in adult rabbit BM does not solely explain the arrest of B lymphopoiesis. However, the interaction of periostin with αvβ3 on lymphoid progenitors probably provides both proliferative and survival signals for cells in the B-cell development pathway.
Improving adherence to NICE guidance for bipolar illness: valproate use in women of childbearing potential
Authors: Mace Shubhra , Taylor David
Published: February 2011

Aims and method

To assess the impact in the South London and Maudsley NHS Foundation Trust of a 20-month quality improvement programme on adherence with National Institute for Health and Clinical Excellence (NICE) recommendations for the use of valproate for bipolar illness in women of childbearing potential.

Results

Significant improvement was noted between baseline and final audit in rates of information provision (10% v. 63%, P < 0.0001), contraceptive use (15% v. 38%, P = 0.0003) and folate prescription (3% v. 35%, P < 0.0001).

Clinical implications

Adherence to guidance can be usefully improved by a sustained intervention programme.
Automated Symptom Alerts Reduce Postoperative Symptom Severity After Cancer Surgery: A Randomized Controlled Clinical Trial
Authors: Cleeland Charles S. , Wang Xin Shelley , Shi Qiuling , Mendoza Tito R. , Wright Sherry L. , Berry Madonna D. , Malveaux Donna , Shah Pankil K. , Gning Ibrahima , Hofstetter Wayne L. , Putnam Joe B. , Vaporciyan Ara A.
Published: February 2011

Purpose

Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control.

Patients and Methods

We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patient's clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling.

Results

The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was −0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control.

Conclusion

Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.
Pre-Enucleation Chemotherapy for Eyes Severely Affected by Retinoblastoma Masks Risk of Tumor Extension and Increases Death From Metastasis
Authors: Zhao Junyang , Dimaras Helen , Massey Christine , Xu Xiaolin , Huang Dongsheng , Li Bin , Chan Helen S.L. , Gallie Brenda L.
Published: February 2011

Purpose

Initial response of intraocular retinoblastoma to chemotherapy has encouraged primary chemotherapy instead of primary enucleation for eyes with clinical features suggesting high risk of extraocular extension or metastasis. Upfront enucleation of such high-risk eyes allows pathologic evaluation of extraocular extension, key to management with appropriate surveillance and adjuvant therapy. Does chemotherapy before enucleation mask histologic features of extraocular extension, potentially endangering the child's life by subsequent undertreatment?

Methods

We performed retrospective analysis of 100 eyes with advanced retinoblastoma enucleated with, or without, primary chemotherapy, in Beijing Tongren Hospital, retrospectively, from October 31, 2008. The extent of retinoblastoma invasion into optic nerve, uvea, and anterior chamber on histopathology was staged by pTNM classification. The treatment groups were compared for pathologic stage (Cochran-Armitage trend test) and disease-specific mortality (competing risks methods).

Results

Children who received chemotherapy before enucleation had lower pTNM stage than primarily enucleated children (P = .01). Five patients who received pre-enucleation chemotherapy died as a result of extension into brain or metastasis. No patients who had primary enucleation died. For children with group E eyes, disease-specific survival (DSS) was lower with pre-enucleation chemotherapy (n = 45) than with primary enucleation (n = 37; P = .01). Enucleation longer than 3 months after diagnosis was also associated with lower DSS (P < .001).

Conclusion

Chemotherapy before enucleation of group E eyes with advanced retinoblastoma downstaged pathologic evidence of extraocular extension, and increased the risk of metastatic death from reduced surveillance and inappropriate management of high-risk disease, if enucleation was performed longer than 3 months after diagnosis.
Glucose-Dependent Changes in SNARE Protein Levels in Pancreatic β-Cells
Authors: Torrejón-Escribano Benjamín , Escoriza Jessica , Montanya Eduard , Blasi Juan
Published: February 2011

Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic β-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule-associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal-associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucose-induced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.
KISS1R Intracellular Trafficking and Degradation: Effect of the Arg386Pro Disease-Associated Mutation
Authors: Bianco Suzy D. C. , Vandepas Lauren , Correa-Medina Mayrin , Gereben Balázs , Mukherjee Abir , Kuohung Wendy , Carroll Rona , Teles Milena G. , Latronico Ana Claudia , Kaiser Ursula B.
Published: February 2011

The goal of this study was to investigate how the Arg386Pro mutation prolongs KiSS-1 receptor (KISS1R) responsiveness to kisspeptin, contributing to human central precocious puberty. Confocal imaging showed colocalization of wild-type (WT) KISS1R with a membrane marker, which persisted for up to 5 h of stimulation. Conversely, no colocalization with a lysosome marker was detected. Also, overnight treatment with a lysosome inhibitor did not affect WT KISS1R protein, whereas overnight treatment with a proteasome inhibitor increased protein levels by 24-fold. WT and Arg386Pro KISS1R showed time-dependent internalization upon stimulation. However, both receptors were recycled back to the membrane. The Arg386Pro mutation did not affect the relative distribution of KISS1R in membrane and internalized fractions when compared to WT KISS1R for up to 120 min of stimulation, demonstrating that this mutation does not affect KISS1R trafficking rate. Nonetheless, total Arg386Pro KISS1R was substantially increased compared with WT after 120 min of kisspeptin stimulation. This net increase was eliminated by blockade of detection of recycled receptors, demonstrating that recycled receptors account for the increased responsiveness of this mutant to kisspeptin. We therefore conclude the following: 1) WT KISS1R is degraded by proteasomes rather than lysosomes; 2) WT and Arg386Pro KISS1R are internalized upon stimulation, but most of the internalized receptors are recycled back to the membrane rather than degraded; 3) the Arg386Pro mutation does not affect the rate of KISS1R trafficking—instead, it prolongs responsiveness to kisspeptin by decreasing KISS1R degradation, resulting in the net increase on mutant receptor recycled back to the plasma membrane.
Sexually Dimorphic Diet-Induced Insulin Resistance in Obese Tissue Inhibitor of Metalloproteinase-2 (TIMP-2)-Deficient Mice
Authors: Jaworski Diane M. , Sideleva Olga , Stradecki Holly M. , Langlois Garret D. , Habibovic Aida , Satish Basanthi , Tharp William G. , Lausier James , LaRock Kyla , Jetton Thomas L. , Peshavaria Mina , Pratley Richard E.
Published: February 2011

Circulating levels of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are altered in human obesity and may contribute to its pathology. TIMP-2 exerts MMP-dependent (MMP inhibition and pro-MMP-2 activation) and MMP-independent functions. To assess the role of TIMP-2 in a murine model of nutritionally induced obesity, weight gain in wild-type and TIMP-2 deficient [knockout (KO)] mice fed a chow or high-fat diet (HFD) was determined. The effects of diet on glucose tolerance and insulin sensitivity, as well as pancreatic β-cell and adipocyte physiology, were assessed. Chow-fed TIMP-2 KO mice of both sexes became obese but maintained relatively normal glucose tolerance and insulin sensitivity. Obesity was exacerbated on the HFD. However, HFD-fed male, but not female, TIMP-2 KO mice developed insulin resistance with reduced glucose transporter 2 and pancreatic and duodenal homeobox 1 levels, despite increased β-cell mass and hyperplasia. Thus, although β-cell mass was increased, HFD-fed male TIMP-2 KO mice develop diabetes likely due to β-cell exhaustion and failure. TIMP-2 mRNA, whose expression was greatest in sc adipose tissue, was down-regulated in HFD-fed wild-type males, but not females. Furthermore, HFD increased membrane type 1-MMP (MMP-14) expression and activity in male, but not female, sc adipose tissue. Strikingly, MMP-14 expression increased to a greater extent in TIMP-2 KO males and was associated with decreased adipocyte collagen. Taken together, these findings demonstrate a role for TIMP-2 in maintaining extracellular matrix integrity necessary for normal β-cell and adipocyte physiology and that loss of extracellular matrix integrity may underlie diabetic and obesogenic phenotypes.
Guinea Pig Kisspeptin Neurons Are Depolarized by Leptin via Activation of TRPC Channels
Authors: Qiu Jian , Fang Yuan , Bosch Martha A. , Rønnekleiv Oline K. , Kelly Martin J.
Published: February 2011

Hypothalamic kisspeptin neurons are critical for driving reproductive function, but virtually nothing is known about their endogenous electrophysiological properties and the effects of leptin on their excitability. Therefore, we used the slice preparation from female guinea pigs to study the endogenous conductances and the effects of leptin on kisspeptin neurons. We targeted the arcuate kisspeptin neurons using visualized-patch whole-cell recording and identified kisspeptin neurons using immuocytochemical staining for kisspeptin or single cell RT-PCR. We also harvested dispersed arcuate neurons for analysis of expression of channel transcripts. Kisspeptin neurons exhibited a relatively negative resting membrane potential, and eighty percent of the neurons expressed a pacemaker current (h-current) and a T-type Ca2+ current. Furthermore, the glutamate receptor agonist N-methyl D-aspartic acid depolarized and induced burst firing in kisspeptin neurons. Leptin activated an inward current that depolarized kisspeptin neurons and increased (burst) firing, but leptin hyperpolarized NPY neurons. Lanthanum, a TRPC-4,-5 channel activator, potentiated the leptin-induced inward current by 170%. The leptin-activated current reversed near −15 mV and was abrogated by the relatively selective TRPC channel blocker 2-APB. The leptin effects were also blocked by a Janus kinase inhibitor, a phosphatidylinositol 3 kinase inhibitor, and a phospholipase Cγ inhibitor. In addition, the majority of these neurons expressed TRPC1 and -5 and phospholipase Cγ1 based on single cell RT-PCR. Therefore, guinea pig kisspeptin neurons express endogenous pacemaker currents, and leptin excites these neurons via activation of TRPC channels. The leptin excitatory effects on kisspeptin neurons may be critical for governing the excitatory drive to GnRH neurons during different nutritional states.
DrosophilaUNC-45 accumulates in embryonic blastoderm and in muscles, and is essential for muscle myosin stability
Authors: Lee Chi F. , Melkani Girish C. , Yu Qin , Suggs Jennifer A. , Kronert William A. , Suzuki Yoko , Hipolito Lori , Price Maureen G. , Epstein Henry F. , Bernstein Sanford I.
Published: February 2011

UNC-45 is a chaperone that facilitates folding of myosin motor domains. We have used Drosophila melanogaster to investigate the role of UNC-45 in muscle development and function. Drosophila UNC-45 (dUNC-45) is expressed at all developmental stages. It colocalizes with non-muscle myosin in embryonic blastoderm of 2-hour-old embryos. At 14 hours, it accumulates most strongly in embryonic striated muscles, similarly to muscle myosin. dUNC-45 localizes to the Z-discs of sarcomeres in third instar larval body-wall muscles. We produced a dunc-45 mutant in which zygotic expression is disrupted. This results in nearly undetectable dUNC-45 levels in maturing embryos as well as late embryonic lethality. Muscle myosin accumulation is robust in dunc-45 mutant embryos at 14 hours. However, myosin is dramatically decreased in the body-wall muscles of 22-hour-old mutant embryos. Furthermore, electron microscopy showed only a few thick filaments and irregular thick–thin filament lattice spacing. The lethality, defective protein accumulation, and ultrastructural abnormalities are rescued with a wild-type dunc-45 transgene, indicating that the mutant phenotypes arise from the dUNC-45 deficiency. Overall, our data indicate that dUNC-45 is important for myosin accumulation and muscle function. Furthermore, our results suggest that dUNC-45 acts post-translationally for proper myosin folding and maturation.
Elastic intramedullary nailing of paediatric fractures of the forearm
Authors: Kang S.-N. , Mangwani J. , Ramachandran M. , Paterson J. M. H. , Barry M.
Published: February 2011

We present the results of 90 consecutive children with displaced fractures of the forearm treated by elastic stable intramedullary nailing with a mean follow-up of 6.6 months (2.0 to 17.6). Eight (9%) had open fractures and 77 (86%) had sustained a fracture of both bones. The operations were performed by orthopaedic trainees in 78 patients (86%). All fractures healed at a mean of 2.9 months (1.1 to 8.7). There was one case of delayed union of an ulnar fracture. An excellent or good functional outcome was achieved in 76 patients (84%). There was no statistical difference detected when the grade of operating surgeon, age of the patient and the diaphyseal level of the fracture were correlated with the outcome. A limited open reduction was required in 40 fractures (44%).

Complications included seven cases of problematic wounds, two transient palsies of the superficial radial nerve and one case each of malunion and a post-operative compartment syndrome. At final follow-up, all children were pain-free and without limitation of sport and play activities.

Our findings indicate that the functional outcome following paediatric fractures of the forearm treated by elastic stable intramedullary nailing is good, without the need for anatomical restoration of the radial bow.
Minimally invasive Oxford phase 3 unicompartmental knee replacement
Authors: Pandit H. , Jenkins C. , Gill H. S. , Barker K. , Dodd C. A. F. , Murray D. W.
Published: February 2011

This prospective study describes the outcome of the first 1000 phase 3 Oxford medial unicompartmental knee replacements (UKRs) implanted using a minimally invasive surgical approach for the recommended indications by two surgeons and followed up independently. The mean follow-up was 5.6 years (1 to 11) with 547 knees having a minimum follow-up of five years. At five years their mean Oxford knee score was 41.3 (sd 7.2), the mean American Knee Society Objective Score 86.4 (sd 13.4), mean American Knee Society Functional Score 86.1 (sd 16.6), mean Tegner activity score 2.8 (sd 1.1). For the entire cohort, the mean maximum flexion was 130° at the time of final review.

The incidence of implant-related re-operations was 2.9%; of these 29 re-operations two were revisions requiring revision knee replacement components with stems and wedges, 17 were conversions to a primary total knee replacement, six were open reductions for dislocation of the bearing, three were secondary lateral UKRs and one was revision of a tibial component. The most common reason for further surgical intervention was progression of arthritis in the lateral compartment (0.9%), followed by dislocation of the bearing (0.6%) and revision for unexplained pain (0.6%). If all implant-related re-operations are considered failures, the ten-year survival rate was 96% (95% confidence interval, 92.5 to 99.5). If only revisions requiring revision components are considered failures the ten-year survival rate is 99.8% (confidence interval 99 to 100).

This is the largest published series of UKRs implanted through a minimally invasive surgical approach and with ten-year survival data. The survival rates are similar to those obtained with a standard open approach whereas the function is better. This demonstrates the effectiveness and safety of a minimally invasive surgical approach for implanting the Oxford UKR.
Entrapment of the sciatic nerve following closed reduction of a dislocated revision total hip replacement
Authors: Chan J. H. H. , Ballal M. S. , Dheerendra S. , Sanchez-Ballester J. , Pydisetty R. V.
Published: February 2011

Injury to the sciatic nerve following closed manipulation of a dislocated total hip replacement is rare. We present such a case in an elderly patient with partial recovery following exploration and release of the nerve.
Combined pelvic osteotomy for the bipartite acetabulum in late developmental dysplasia of the hip
Authors: Rejholec M.
Published: February 2011

In late developmental dysplasia of the hip in childhood, the deformed dysplastic acetabulum is malaligned and has lost its shape due to pressure from the subluxed femoral head. The outer part of the acetabulum involves the upper part of the original acetabulum, thereby giving a bipartite appearance. A clear edge separates the outer from inner part which represents the lower part of the original acetabulum and has no direct contact with the femoral head.

Combined pelvic osteotomy (CPO) using a Lance acetabuloplasty with either a Salter or a Pemberton procedure restores the original shape and realigns the acetabulum. A total of 20 children (22 hips), with a mean age of 46 months (28 to 94) at primary operation underwent CPO with follow-up for between 12 and 132 months.

In each case concentric stable reduction with good acetabular cover was achieved and maintained throughout the period of follow-up.
New methods for the synthesis of certain alkaloids and terpenoids
Authors: Banwell Martin G. , Lehmann Anna L. , Menon Rajeev S. , Willis Anthony C.
Published: February 2011

The use of ring-fused gem-dihalocyclopropanes, Au(I)-catalyzed cyclization reactions, and chemoenzymatic techniques in the synthesis of natural products is described.
Different Expression Patterns of Ngb and EPOR in the Cerebral Cortex and Hippocampus Revealed Distinctive Therapeutic Effects of Intranasal Delivery of Neuro-EPO for Ischemic Insults to the Gerbil Brain
Authors: Gao Yan , Mengana Yuneidis , Cruz Yamila Rodríguez , Muñoz Adriana , Testé Iliana Sosa , García Jorge Daniel , Wu Yonghong , Rodríguez Julio César García , Zhang Chenggang
Published: February 2011

The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the “golden hour” of about 60 min and the “silver day” of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus.
Vehicle Emissions and Fuel Economy Effects of 16 % Butanol and Various Ethanol Blended Fuels (E10, E20, and E85)
Authors: Schulz Melissa , Clark Shaleen
Published: February 2011

Due to various concerns involving conventional gasoline, there has been a growing interest in the study of alternative fuels and their use in the automotive industry. There has been particular interest in the fuel effects of varying levels of ethanol blends and other alternative fuels on vehicle emissions and fuel economy. This paper will examine and compare both exhaust emissions and fuel economy for various ethanol blended fuels, and a 16 % butanol blended fuel. The results were generated using the U.S. Federal Test Procedure. Vehicles that are certified to U.S., European, and Brazilian government standards were tested. These vehicles include a flex fuel capable (FFV) 2007 Chevrolet Zafira (E100-FFV), 2007 Chevrolet Suburban (E85-FFV), 2007 Saab 9-5 BioPower (E85-FFV), 2007 Chevrolet Suburban, 2007 Pontiac G5, and a 2006 Pontiac G6. The fuels examined were E10, E20, E85, and Bu16. Each fuel was splash blended to make up the proper finished fuel blend. Fuel economy and emissions results from these fuels were compared with those from Tier 2 Emissions Certification fuel.