bluuebunny/crossref_metadata_2025 huggingface dataset:
17-Allylamino-17-Demethoxygeldanamycin and MEK1/2 Inhibitors Kill GI Tumor Cells via Ca2+-Dependent Suppression of GRP78/BiP and Induction of Ceramide and Reactive Oxygen Species
Authors: Walker Teneille , Mitchell Clint , Park Margaret A. , Yacoub Adly , Rahmani Mohamed , Häussinger Dieter , Reinehr Roland , Voelkel-Johnson Christina , Fisher Paul B. , Grant Steven , Dent Paul
Published: May 2010

The present studies determine in greater detail the molecular mechanisms upstream of the CD95 death receptor by which geldanamycin heat shock protein 90 inhibitors and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) inhibitors interact to kill carcinoma cells. MEK1/2 inhibition enhanced 17-allylamino-17-demethoxygeldanamycin (17AAG) toxicity that was suppressed in cells deleted for mutant active RAS that were nontumorigenic but was magnified in isogenic tumorigenic cells expressing Harvey RAS V12 or Kirsten RAS D13. MEK1/2 inhibitor and 17AAG treatment increased intracellular Ca2+ levels and reduced GRP78/BiP expression in a Ca2+-dependent manner. GRP78/BiP overexpression, however, also suppressed drug-induced intracellular Ca2+ levels. MEK1/2 inhibitor and 17AAG treatment increased reactive oxygen species (ROS) levels that were blocked by quenching Ca2+ or overexpression of GRP78/BiP. MEK1/2 inhibitor and 17AAG treatment activated CD95 and inhibition of ceramide synthesis; ROS or Ca2+ quenching blocked CD95 activation. In SW620 cells that are patient matched to SW480 cells, MEK1/2 inhibitor and 17AAG toxicity was significantly reduced, which correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and enhanced tumor cell killing. Inhibition of ceramide signaling abolished drug-induced ROS generation but not drug-induced cytosolic Ca2+ levels. Thus, treatment of tumor cells with MEK1/2 inhibitor and 17AAG induces cytosolic Ca2+ and loss of GRP78/BiP function, leading to de novo ceramide synthesis pathway activation that plays a key role in ROS generation and CD95 activation. Mol Cancer Ther; 9(5); 1378–95. ©2010 AACR.
Randomized Controlled Trial of Hyaluronic Acid/Carboxymethylcellulose Dressing after Endoscopic Sinus Surgery
Authors: Woodworth Bradford A. , Chandra Rakesh K. , Hoy Mark J. , Lee Fu-shing , Schlosser Rodney J. , Gillespie M. Boyd
Published: May 2010

Objective: To determine if a hyaluronic acid/carboxymethylcellulose (HA/CMC) sinus dressing reduces the rate of postoperative scarring. Methods: In a randomized, matched-controlled, single-blinded study, following the completion of surgery, an HA/CMC dressing was randomly assigned to one side with the opposite unpacked side serving as a control. Results: Fifty-three patients underwent surgery for chronic rhinosinusitis (CRS; 39 patients) or CRS with nasal polyposis (14 patients). At the 8-week follow-up, there was no difference in synechiae on the HA/CMC side compared to the control (p = 0.09). HA/CMC-treated sinuses, however, demonstrated fewer synechiae in the first 2 weeks postoperatively compared to the control (p = 0.01), and were associated with significantly less nasal congestion at the 4-week (p = 0.02) and 8-week follow-up visits (0.03). Conclusion: There was no long-term difference in the rate of synechiae in the HA/CMC-treated sinus compared to the control. However, less severe nasal congestion and synechiae in the initial postoperative period may reduce the need for aggressive sinus debridement.
Effects of Natalizumab on Circulating B Cells, T Regulatory Cells and Natural Killer Cells
Authors: Putzki Norman , Baranwal Manoj Kumar , Tettenborn Barbara , Limmroth Volker , Kreuzfelder Ernst
Published: May 2010

Background: Natalizumab is a humanized monoclonal antibody directed against very late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple sclerosis. Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance. Methods: Longitudinal ex vivo and in vitro study to determine the effect of natalizumab on the frequency of distinct immune cells and on the frequency and suppressive function of natural CD4+CD25+ regulatory T cells (Tregs). Results: Natalizumab binding to VLA-4 was more marked for B cells than for T cells (49% reduction in VLA-4-expressing B cells compared to 24.5% reduction of T cells). There was an increase in circulating B cells over T cells (2.6 vs. 1.5 fold, p < 0.001). Natural killer cells increased 1.5-fold (p = 0.01). Natalizumab led to a relative decrease in CD4+CD25+ Tregs from 18.9 to 14.1% (p = 0.04). The impaired suppressive capacity of Tregs was not restored. Conclusion: Natalizumab reduces VLA-4 expression on all investigated immune cells, but changes were most marked for B cells. Further differential effects on immune cells may be relevant to opportunistic central nervous system infections during treatment with natalizumab.
Ventriculoperitoneal Shunt Complications: A Three-Year Retrospective Study in a Kenyan National Teaching and Referral Hospital
Authors: Mwachaka Philip M. , Obonyo Nchafatso G. , Mutiso Ben K. , Ranketi Simeon , Mwang’ombe Nimrod
Published: May 2010

Background/Aims: Ventriculoperitoneal shunt complications have scarcely been reported in sub-Saharan Africa. This study aimed at determining the frequency of these complications and their associated risk factors in a Kenyan National Teaching and Referral Hospital. Methods: This cross-sectional study retrospectively covered 117 patients admitted to the Kenyatta National Hospital neurosurgical ward between January 2005 and December 2007 with ventriculoperitoneal shunt complications. The data obtained were analysed using the Statistical Package for the Social Sciences. Results: The most common complication was obstruction in 63 patients (53.8%), followed by migration in 25 (21.4%) and infection in 23 (19.7%) of the patients. Up to 49.6% of the complications occurred in patients younger than 6 months. Multiple complications were seen in 23.9% of the cases. The mean shunt duration was 18.05 months. Positive correlations existed between the presence of a shunt complication and patient age, shunt duration and the number of complications developed. These correlations were, however, neither strong nor statistically significant. Conclusion: This study reports the highest frequencies of shunt obstruction and migration ever recorded in the literature. The high rate of development of multiple shunt failures coupled with a short shunt duration calls for a closer monitoring of patients with ventriculoperitoneal shunts.
Prognostic Factors in Patients with Occipital Encephalocele
Authors: Kıymaz Nejmi , Yılmaz Nebi , Demir İsmail , Keskin Sıddık
Published: May 2010

Background: An encephalocele is a herniation of the brain and the meninges through a skull defect protruding towards the exterior. The condition is not rare when compared to spinal dysraphisms, but the worldwide incidence is not precisely known. The cases involving occipital encephaloceles which we have diagnosed in our clinic and the surgical approaches for this rare condition are presented herein. Methods: Thirty patients who were diagnosed with occipital encephaloceles and referred to our Neurosurgery Clinic at the Yuzuncu Yil University, Faculty of Medicine Research Hospital between 2000 and 2009 were enrolled in this study. The age of the patient, size of the sac, pathologies that accompanied the condition, and treatments applied were assessed. Results: In the present study, 30 patients (22 girls and 8 boys), whose ages varied between newborn and 14 months, were evaluated. The encephalocele sac was located in the occipital region in 27 patients (90%) and in the occipitocervical region in 3 patients (3%). Nine (30%) of the 30 patients died; 2 in the preoperative period, 2 in the postoperative early period (0–7 days) and 5 in the late postoperative period (first week to 3 months). With the exception of the 2 patients who died preoperatively, surgery was performed on all of the patients. The mortality rate in our study was 29%. Conclusions: Our study demonstrated that factors which determine the prognosis of patients diagnosed with occipital encephaloceles include the size of the sac, the contents of the neural tissue, hydrocephaly, infections, and pathologies that accompany the condition. An occipital encephalocele is a congenital neurologic condition with an extremely high morbidity and mortality in spite of the treatments rendered pre- and postoperatively.
Variability of Two Plaque Sampling Methods in Quantitation of Streptococcus mutans
Authors: Hsu K.-L.C. , Osgood R.C. , Cutter G.R. , Childers N.K.
Published: May 2010

The aim of this study was to determine the reproducibility of individual versus pooled plaque sampling of permanent first molars (PFM) to quantitate Streptococcus mutans (SM)/total streptococci (TS). Ten individual and pooled plaque samples were collected from 35 subjects, randomly assigned to individual-first or pooled-first group. Plaque samples were processed and quantified for SM and TS. SM/TS ratio was used to determine the reproducibility within two group samples. Mean percentage of SM/TS in both methods were not significantly different. However, within subject detection of SM was found to be significantly more sensitive for individual sampling method. Despite the lack of a difference between both methods for SM/TS quantitation, the difference in SM detection suggests that individual sampling is more sensitive.
Prevalence and Risk Indicators of Erosion in Thirteen- to Fourteen-Year-Olds on the Isle of Man
Authors: Bardolia P. , Burnside G. , Ashcroft A. , Milosevic A. , Goodfellow S.A. , Rolfe E.A. , Pine C.M.
Published: May 2010

Aims: The aim was to determine the prevalence of erosion in 13- to 14-year-old children on the Isle of Man and to investigate the strength of association with dietary risk factors. Methods: Exposed dentine was assessed on smooth surfaces of incisors/canines and occlusal surfaces of first molars. A questionnaire assessed the consumption frequency of foodstuffs. Results: Of 629 children examined, 124 (20%) had dentine exposed labially, palatally or occlusally. More males had dentine exposed on these surfaces (OR = 1.7, 95% CI = 1.2–2.6). Palatal dentine exposure was present in 3% of the children and occlusal dentine exposure in 18%. In bivariate analyses, drinking fizzy drinks more than once a day was associated with erosion (OR = 1.6, 95% CI = 1.1–2.3). The mean DMFT scores were not statistically different for the children with smooth surface/occlusally exposed dentine (1.37) compared to those without (1.58). Multiple regression analysis showed age, gender and toothbrushing to be significant predictors of erosion. Conclusion: This study has found a higher proportion of 13- to 14-year-old children with exposed dentine in molars than previous studies. The results corroborate previous reports that males have more erosion than females.
Prevalence of Allelic Loss at TP53 in Endometrial Carcinomas
Authors: Semczuk Andrzej , Schneider-Stock Regine , Szewczuk Wiktor
Published: May 2010

Alterations within the TP53 tumor suppressor belong to the most common genetic features reported in various human neoplasms, including endometrial cancer. In this article, the prevalence of allelic loss at the TP53 locus in primary human endometrial carcinomas (ECs) is discussed. Furthermore, we reviewed the role of allelic imbalance at 17p13.1 in metastatic human ECs on the basis of a literature review and on recently published data ascertained by our laboratory staff.
Comparison of the Long-Term Safety and Efficacy of Drug-Eluting and Bare-Metal Stent Implantation in Saphenous Vein Grafts
Authors: Latib Azeem , Ferri Luca , Ielasi Alfonso , Cosgrave John , Godino Cosmo , Bonizzoni Erminio , Romagnoli Enrico , Chieffo Alaide , Valgimigli Marco , Penzo Carlo , Carlino Mauro , Michev Iassen , Sangiorgi Giuseppe M. , Montorfano Matteo , Airoldi Flavio , Colombo Antonio
Published: May 2010

Background—

Concerns about the long-term safety of drug-eluting stents (DES) in saphenous vein grafts has become an area of controversy and uncertainty.

Methods and Results—

In this retrospective registry, we compared the outcomes in 127 patients (143 lesions) treated with DES from April 2002 to June 2006 (DES group) with 131 patients (160 lesions) treated with bare-metal stents in the preceding 36 months (bare-metal stent group). End points analyzed were cumulative death, myocardial infarction, and target vessel revascularization at 2 years after stent implantation. The DES group was significantly (
P
<0.05) more complex with a greater frequency of diabetes (33.1%versus 15.3%), older grafts (11.6±5.3 years versus 9.6±5.2 years), restenotic lesions (23.8% versus 4.4%), total occlusions (7.7% versus 1.2%), and smaller grafts (3.16±0.66 mm versus 3.44±0.76 mm) treated with longer stents (34.1±25.1 mm versus 22.7±11.6 mm). At 2 years, there was no statistical difference in death (8.7% versus 7.8%), myocardial infarction (6.3% versus 9.4%), or target vessel revascularization (19.7% versus 24.2%) between DES and bare-metal stents, respectively. A propensity analysis to adjust for baseline differences suggested that there was no observed association between DES and increased mortality (hazard ratio, 0.72; 95% CI, 0.21 to 2.44;
P
=0.60) but possibly an association with a reduction in target vessel revascularization (hazard ratio, 0.31; 95% CI, 0.14 to 0.66;
P
=0.002).

Conclusions—

Despite being implanted in patients and lesions more complex than the bare-metal stent group, there was no observed association between DES implantation in saphenous vein grafts and an increase in late mortality. DES may maintain their efficacy in reducing revascularization rates in diseased saphenous vein grafts over a 2-year follow-up period.
Elaboration on Specialization in Crime
Authors: Yonai Shachar , Levine Stephen Z. , Glicksohn Joseph
Published: May 2010

To elaborate past research, this study examines the course of specialization and versatility with maturation and contends that specialization develops in a nonrandom manner, as suggested by the orthogenic principle of human development. To examine the development of specialization and versatility, forward specialization coefficients were disaggregated for three age cohorts over a 20-year follow-up period in a sample of high-risk youth ( n = 3,652) with 54,175 arrests. Results show that forward specialization coefficients were generally of moderate magnitude and, across age cohorts, developed modestly in an age-graded manner for the youngest cohort. In conclusion, the results provide preliminary support for the orthogenic theory among early first-admission youth.
The feasibility of assessing alcohol use among college students using wireless mobile devices: Implications for health education and behavioural research
Authors: Mays Darren , Cremeens Jennifer , Usdan Stuart , Martin Ryan J , Arriola Kimberly J , Bernhardt Jay M
Published: May 2010

Objective: This study examined the feasibility of using wireless mobile devices (MDs) to collect daily alcohol information among college students, in particular examining feasibility in the context of costs associated with the use of wireless MDs. This study reports on practical aspects of using MDs to collect alcohol data, including compliance, technical success, user preferences for completing MD-based assessments, and cost.

Setting: The study took place at a large, public university in the south-eastern United States.

Design: A two-group, randomized design was used. A daily assessment of alcohol use administered using wireless MDs was completed by a group of college students ( n=86) for 30 days and compared to a paper-based (PB) daily assessment of alcohol use completed by a second group of college students ( n=83) over the same time period.

Results: Completion rates for the MD assessment (85.8 per cent) were comparable to the PB assessment (97.6 per cent) given the differences in mode of administration. Participants found the MDs easy to use (83.7 per cent), easy to read (94.2 per cent), and on average liked completing the daily MD assessment ( M 4.47, SD 1.16) significantly more than respondents liked completing the PB assessment ( M 3.88, SD 1.08; t [164] 3.84, p < 0.001). Few participants in the MD group reported that they were uncomfortable (9.3 per cent) or nervous (2.3 per cent) completing daily assessments using the MDs.

Conclusion: Results indicate that the feasibility of using MDs for data collection may be influenced by user preferences and should be tested on different health behaviours in more diverse populations.
Randomized controlled trial to increase physical activity among insufficiently active women following their participation in a mass event
Authors: Lane Aoife , Murphy Niamh , Bauman Adrian , Chey Tien
Published: May 2010

Objective: To assess the impact of a community based, low-contact intervention on the physical activity habits of insufficiently active women.

Design: Randomized controlled trial.

Participants: Inactive Irish women.

Method: A population sample of women participating in a mass 10 km event were up followed at 2 and 6 months, and those who had relapsed to insufficient levels of physical activity were recruited to this trial and randomly allocated to an intervention or control group. A tailored physical activity booklet was mailed to participants in the intervention group; a placebo booklet was administered to the control group. Three weeks after the dissemination of materials, members of the intervention group were contacted by phone to check the receipt and use of the booklets. Six weeks post baseline, questionnaires were administered to all participants.

Results: Receipt and use of materials and an increase in self-efficacy was significantly greater in the intervention group. Mean total physical activity increased significantly between baseline and follow-up in both the intervention (+ 109 min) and control groups (+ 139 min), with increases most apparent among the least active participants of both groups. There was also a significant increase in the number of respondents meeting minimum physical activity guidelines at follow-up.

Conclusion: There was no difference in the increases in physical activity, which were greatest among least active participants, between intervention and control groups, suggesting that the tailored materials used in this trial did not have a greater impact than standard health information and contact alone.
Adolescents’ preferences regarding sex education and relationship education
Authors: Turnbull Triece , van Schaik Paul , van Wersch Anna
Published: May 2010

Objective: The aim of the current study was to examine adolescents’ perceptions of the quality of a Sex and Relationship Education (SRE) intervention, their preferences for sources of SRE and how these vary as a function of gender, school’s faith and school type.

Design: A non-experimental design was used.

Setting: The participants ( N = 759 adolescent girls [ n = 448] and boys [ n = 326]), who had attended an SRE intervention and had previously been given formal SRE within the school they attended, completed a survey questionnaire.

Method: A questionnaire was designed to assess perceptions and preference of the intervention. The data were analysed using logistic regression.

Results: Adolescents judged the sex education intervention to be of high quality and enjoyed being taught by sexual-health workers. Preferred sources of SRE included sexual-health workers, parents and peers as well as the media. Gender, school’s faith (Church of England or Catholic) and school type (mainstream, special needs) were predictors of preference for various aspects of SRE.

Conclusion: The results highlight the crucial role of experienced qualified SRE educators, but also the supplementary role of parents and peers as well as the auxiliary role of Internet sites, magazines, phone lines and schools. Stereotypical preferences of boys and girls outside SRE seem to be perpetuated in SRE, and special needs and mainstream adolescents’ preferences are consistent with their communication and education outside SRE.
Organizational Learning and Reform at the New York City Police Department
Authors: Sugarman Barry
Published: May 2010

This article offers two contributions to the literature of organizational learning (OL): (a) a multifaceted case study of the New York City Police Department (NYPD) and (b) a framework for future research in OL. The NYPD case is analyzed using two of the four alternative definitions of OL that are highlighted here. One is sharply focused on bottom line results; the other is more inclusive and more suitable for assessing an organization’s capacity for renewal and hence for sustainable success. Nine examples from the case illustrate nine different forms of OL, which are mapped onto the four alternative definitions. This article has major implications for how OL should be defined.
What is optimal flow using a mini-bypass system?
Authors: Fernandes P. , MacDonald J. , Cleland A. , Walsh G. , Mayer R.
Published: May 2010

The purpose of this study is to determine the appropriate arterial pump flow /cardiac index (CI) utilizing a mini-bypass system. The unique feature of most mini-bypass systems is that the centrifugal pump combines the function of kinetic venous drainage with arterial pump flow. Therefore, if drainage is reduced, arterial pump flow is also reduced. Managing this system can present challenges to the clinical perfusionist. We reviewed fifteen cases, using the Medtronic Resting Heart System (RHS). This retrospective study examined the arterial pump flow, measured as cardiac index (CI), mean arterial pressure, inlet venous saturation, urine output, vasopressor use, and lactate production during routine cardiac surgery. The mean cardiac index for all patients was 1.90 +/- 0.14, range 1.63-2.08 L/min/m2. The mean hemoglobin on cardiopulmonary bypass (CPB) was 10.6 +/- 1.2, with a range of 9.2-13.3 g/dL. The lactate produced on CPB was 2.03 +/-0.67 with a range of 1.5-3.5 mmol/L. The mean change in lactate measured from pre CPB to post CPB was 0.85 +/- 0.71 with a median lactate of 0.6 mmol/L. The venous saturation was 65.53 +/- 6.03% with a median of 65% and a range of 57-82%. The mean arterial pressure was 67.04 +/- 10.45 mmHg with a median of 62.5 mmHg. The median urine output was 125 mls. The vasopressor median was 2200 µg. All patients were maintained on CPB with a mean nasopharyngeal temperature of 35.43° Celsius. Despite using lower than predicted flows, it would appear that adequate perfusion is provided. The higher hemoglobin content achieved through reduced hemodilution and reduced inflammation appears to enable this system to deliver adequate flow and perfusion at reduced cardiac indices. This research provides evidence which challenges longstanding beliefs that a cardiac index of 2.4 L/min/m2 is required for all cases.
Quantitative Magnetic Resonance Imaging Detects Changes in Meniscal Volume In Vivo After Partial Meniscectomy
Authors: Bowers Megan E. , Tung Glenn A. , Oksendahl Heidi L. , Hulstyn Michael J. , Fadale Paul D. , Machan Jason T. , Fleming Braden C.
Published: May 2010

Background: Quantifying changes in meniscal volume in vivo before and after partial meniscectomy (PM) could help elucidate the mechanisms involved in osteoarthritis development after meniscal injury and its surgical treatment.

Purpose/Hypothesis: To determine whether quantitative magnetic resonance imaging (qMRI) can detect the immediate reduction in meniscal volume created by PM, while ruling out changes in unresected structures. We hypothesized that qMRI would be reliable for determining meniscal volume within the repeated images of unresected menisci. Additionally, we expected no significant difference in volume between the uninjured menisci of the injured knees and the same menisci of the uninjured knees.

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

Methods: Ten subjects with meniscal tears were evaluated with 3-T MRI before and after arthroscopic PM. Manual segmentation was used to create models of the menisci and to determine the preoperative and postoperative meniscal volumes for each subject. The responsiveness and reliability of qMRI for determining meniscal volume in vivo were evaluated using these measurements. We expected a decrease in volume of the resected menisci, but not in the uninjured menisci, after surgery.

Results: The mean preoperative volume of the injured menisci was significantly greater than the mean postoperative volume (2896 ± 277 vs 2480 ± 277 mm3; P = .000). There was no significant difference between the mean preoperative and postoperative volumes of the uninjured menisci (2687 ± 256 vs 2694 ± 256 mm3; P = 1.000).

Conclusion: Manual segmentation demonstrated a significant reduction in the volume of the surgically resected menisci after PM, but no significant change in the volume of unresected meniscal tissue, indicating that the manual segmentation method is responsive.

Clinical Relevance: This approach offers a novel, reliable method to study the relationship between the volume of meniscal tissue removed during PM and subsequent patient outcomes during long-term clinical studies.
Statistical models for the control phase of clinical monitoring
Authors: Stevens Richard J , Oke Jason , Perera Rafael
Published: May 2010

The rise in the prevalence of chronic conditions means that these are now the leading causes of death and disability worldwide, accounting for almost 60% of all deaths and 43% of the global burden of disease. Management of chronic conditions requires both effective treatment and ongoing monitoring. Although costs related to monitoring are substantial, there is relatively little evidence on its effectiveness. Monitoring is inherently different to diagnosis in its use of regularly repeated tests, and increasing frequency can result in poorer rather than better statistical properties because of multiple testing in the presence of high variability. We present here a general framework for modelling the control phase of a monitoring programme, and for the estimation of quantities of potential clinical interest such as the ratio of false to true positive tests. We show how four recent clinical studies of monitoring cardiovascular disease, hypertension, diabetes and HIV infection can be thought as special cases of this framework; as well as using this framework to clarify the choice of estimation and calculation methods available. Noticeably, in each of the presented examples over-frequent monitoring appears to be a greater problem than under-frequent monitoring. We also present recalculations of results under alternative conditions, illustrating conceptual decisions about modelling the true or observed value of a clinical measure.
Effectiveness of end-of-life education among community-dwelling older adults
Authors: Matsui Miho
Published: May 2010

The purpose of this study was to evaluate the effectiveness of an educational intervention regarding end-of-life discussion directed at older Japanese adults and their attitude to and acceptance of this intervention. A quasi-experimental design was used. A total of 121 older adults, aged 65 years and over, consented to participate. Data from 55 intervention and 57 control participants were used for the analysis. The intervention consisted of an education program comprising a video, a lecture using a handout, and discussion among participants. The control group received only the handout. Both groups were followed up after one month. The intervention group’s attitude became more favorable towards advance directives, especially living wills (P = 0.024). In addition, their expression of preference for life-sustaining treatment by means of artificial nutrition was less at follow up, demonstrating that these older adults had become more autonomous (P = 0.008). There was greater acceptance of the intervention as a whole by the intervention group compared with the control group (P = 0.011). Although few participants overall completed living wills, at follow up twice as many in the intervention group had discussed end-of-life matters with family members and/or their physician.
The Stories of Young People Living With a Liver Transplant
Authors: Taylor Rachel M. , Franck Linda S. , Dhawan Anil , Gibson Faith
Published: May 2010

Adolescence is a difficult time for those with chronic illness because of the constraints of the illness on developmental tasks. Little is known about the impact liver transplantation has during adolescence. In this study we aimed to explore, in their own words, young people’s lived experience of life after transplantation. We used semistructured interviews to collect narrative data, and used a purposive sample of 14 young people in early, middle, and late adolescence, transplanted for a range of chronic, acute, and metabolic liver diseases. We analyzed the transcripts using a framework in which analysis progresses through a five-stage process of matrices. Six main themes emerged, related to relationships, affect on schooling, tiredness and fatigue, acceptance of the burden of medication, communication with health professionals, and view of the future. These findings add new insight into the transplantation experience, which might lead to improvements in care and help direct further research in this important aspect of clinical care.
Opinion Networks Among Long-Term Care Specialists
Authors: Clark Melissa A. , Linkletter Crystal D. , Xiaozhong Wen  , Miller Edward Alan , Mor Vincent
Published: May 2010

A challenge in the adoption of long-term care (LTC) policy reform is the number of constituency groups active in LTC and historical antagonism among these groups regarding critical issues such as LTC financing and regulation. As part of a national survey of LTC specialists, the authors asked previously identified specialists to nominate other “experts” with known or demonstrable experience in LTC. As a proxy for potential information exchange, data about nominations were used to construct and describe the networks of LTC specialists representing consumer advocates, provider representatives, public officials, policy experts, and others. Associations between network characteristics and attitudes about LTC policy reform were also examined. Individuals tended to nominate other people within their same constituency group as experts. Academic and research-based policy experts were most likely to be classified as prominent network members. Network structure was associated with attitudes toward LTC financing but not the regulation of nursing homes.
Beliefs About Wife Beating: An Exploratory Study With Lebanese Students
Authors: Obeid Nadine , Chang Doris F. , Ginges Jeremy
Published: May 2010

In recent years, there has been a growing interest in understanding the sociocultural contexts and risk factors for domestic violence in the Arab world. This study provides an analysis of the religious, legal, and familial contexts of domestic violence in Lebanon and assesses contemporary attitudes toward women and wife beating in a sample of 206 Lebanese university students. Gender, patriarchal attitudes, religion, childhood experiences with family violence, and mother’s employment status were investigated as predictors of attitudes toward wife beating. Consistent with feminist theories of wife abuse, gender and attitudes toward women’s roles emerged as the strongest predictors of beliefs about wife beating.
Actor-Network Theory, organizations and critique: towards a politics of organizing
Authors: Alcadipani Rafael , Hassard John
Published: May 2010

In recent years the approach to social theory known as Actor-Network Theory (ANT) has been adopted within a range of social science fields. Despite its popularity, ANT is considered a controversial approach in that it appears to promote a sociological perspective that lacks substantive political critique. This is argued to be particularly true in ANT’s ‘translations’ in management and organization studies (MOS). In this article, we argue that the ‘ANT and After’ literature offers the potential to develop such a political critique. In particular we suggest it presents the opportunity to develop an approach that de-naturalizes organization(s), has the ability to deliver critical performativity, and at the same time offer a reflexive approach to management and organizational knowledge. Using organizational examples, we argue that ANT and After can offer insights relevant to the development of a critical perspective on MOS, notably through its advocacy of a ‘political ontology’ of organizing.
Public images of leaders of anti-immigration parties: Perceptions of legitimacy and effectiveness
Authors: Bos Linda , van der Brug Wouter
Published: May 2010

In the last two decades several anti-immigration parties have risen in Western Europe. Some of these parties have been very successful in elections, whereas others have been rather unsuccessful. Some scholars have argued that this success depends in part on the extent to which voters perceive these parties (and their leaders) as legitimate (not violent or undemocratic) and as effective. However, no studies exist that test the effect of these public perceptions on electoral support. We fill this void by proposing operationalizations of voters’ perceptions of parties in terms of legitimacy and effectiveness. These operationalizations were employed to measure public perceptions of leaders of two anti-immigration parties and leaders of four established parties that participated in the Dutch national parliamentary elections of 2006. The analyses of these data (n = 382) demonstrate the significance of measuring public images directly and show that legitimacy and effectiveness are important predictors of support for anti-immigration parties. Prior research showed that voters evaluate anti-immigration parties largely by the same criteria as they use to evaluate other parties. Our study demonstrates that this is only true when voters consider an anti-immigration party as effective and legitimate.
Emerging personal media genres
Authors: Lüders Marika , Prøitz Lin , Rasmussen Terje
Published: May 2010

In this article we argue that the concept of genre has a valuable function within sociological theory, particularly for understanding emerging communicative practices within social and personal media. Genres span the whole range of recognizable forms of communication, play a crucial role in overcoming contingency and facilitate communication. Their function is to enhance composing and understanding of communication by offering interpretative, recognizable and flexible frames of reference. As such, genres generate a sense of stability in modern complex societies. Genres ought to be seen as an intermediary level between the levels of media and text, however influenced by both. They operate as interaction between two interdependent dimensions, conventions and expectations, both of which are afforded by media and specific texts. In this article these relationships are illustrated through two cases of emerging personal media genres: the online diary and the camphone self-portrait.
Podologues: conversations created by science podcasts
Authors: Birch Hayley , Weitkamp Emma
Published: May 2010

Podcasts are media files that can be automatically aggregated and downloaded via the internet, and transferred to portable media players. Combined with online discussion facilities, podcasts represent flexible and potentially valuable tools for communicating about science. This pilot project aimed to assess the role of science podcasts in stimulating discussions, or ‘podologues’, about science through detailed analyses of a sample of five popular science podcasts. Two main methods were used: content analysis of online discussion forums and blogs associated with the five podcasts and interviews with listeners. The results show that podcasts are regarded as valuable sources of scientific information by listeners and that blogs and forums can act as public spaces for audience members to share knowledge, develop their own ideas about science and provide feedback to media producers. Larger, more detailed studies are required to further understand the value of podcasts for stimulating public discourse about science.
Distributed Curriculum Leadership in Action: A Hong Kong Case Study
Authors: Law Edmond , Galton Maurice , Wan Sally
Published: May 2010

This study was designed primarily to investigate the impact of school-based curriculum development teams on teacher development within the tradition of school-based curriculum development. The results are expected to provide valuable insights for teachers, school management and policy making. Teacher interviews in a primary school in Hong Kong were conducted to evaluate the extent to which teacher engagement in curriculum decision-making processes, which are within two school-based curriculum development teams, led to teacher professional development; these were triangulated with video-taped meetings and tryout lessons. Qualitative evidence showed that participating teachers have each undergone professional development through the processes involved in the planning, experimenting and reflecting (PER) model, which is also upon curriculum practice and innovation under certain conditions. However, the complex structures and processes that have been established to involve teachers in curriculum decision making need further empirical and theoretical work. While previous papers on the studies focused on teacher development and pupil learning, this paper, based on interview data, aims to focus on the functions of distributed leadership, and how the leadership styles of consultants and panel heads mediate the interactional patterns and therefore the discourses in the Mathematics and Chinese development teams in the second action cycle of the innovation project.
Endothelial protein C receptor–expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver
Authors: Iwasaki Hiroko , Arai Fumio , Kubota Yoshiaki , Dahl Maria , Suda Toshio
Published: May 2010

Hematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR+ HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR+ cells were localized adjacent to, or integrated in, the Lyve-1+ sinusoidal network, where APC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR+ HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR+ HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1+ cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR+ HSCs resided in the perisinusoidal niche in mouse FL.
Influence of bone marrow stromal microenvironment on forodesine-induced responses in CLL primary cells
Authors: Balakrishnan Kumudha , Burger Jan A. , Quiroga Maite P. , Henneberg Marina , Ayres Mary L. , Wierda William G. , Gandhi Varsha
Published: May 2010

Forodesine, a purine nucleoside phosphorylase inhibitor, displays in vitro activity in chronic lymphocytic leukemia (CLL) cells in presence of dGuo, which is the basis for an ongoing clinical trial in patients with fludarabine-refractory CLL. Initial clinical data indicate forodesine has significant activity on circulating CLL cells, but less activity in clearing CLL cells from tissues such as marrow. In tissue microenvironments, lymphocytes interact with accessory stromal cells that provide survival and drug-resistance signals, which may account for residual disease. Therefore, we investigated the impact of marrow stromal cells (MSCs) on forodesine-induced response in CLL lymphocytes. We demonstrate that spontaneous and forodesine-induced apoptosis of CLL cells was significantly inhibited by human and murine MSCs. Forodesine-promoted dGuo triphosphate (dGTP) accumulation and GTP and ATP depletion in CLL cells was inhibited by MSCs, providing a mechanism for resistance. Also, MSCs rescued CLL cells from forodesine-induced RNA- and protein-synthesis inhibition and stabilized and increased Mcl-1 transcript and protein levels. Conversely, MSC viability was not affected by forodesine and dGuo. Collectively, MSC-induced biochemical changes antagonized forodesine-induced CLL cell apoptosis. This provides a biochemical mechanism for MSC-derived resistance to forodesine and emphasizes the need to move toward combinations with agents that interfere with the microenvironment's protective role for improving current therapeutic efforts.
Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
Authors: Becker Heiko , Marcucci Guido , Maharry Kati , Radmacher Michael D. , Mrózek Krzysztof , Margeson Dean , Whitman Susan P. , Paschka Peter , Holland Kelsi B. , Schwind Sebastian , Wu Yue-Zhong , Powell Bayard L. , Carter Thomas H. , Kolitz Jonathan E. , Wetzler Meir , Carroll Andrew J. , Baer Maria R. , Moore Joseph O. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D.
Published: May 2010

We previously reported the adverse prognostic impact of Wilms tumor 1 gene (WT1) mutations in younger adult cytogenetically normal acute myeloid leukemia (CN-AML). Here, we investigated 243 older (≥ 60 years) primary CN-AML patients. WT1 mutated (WT1mut) patients (7%) had FLT3-ITD more frequently (P < .001), lower hemoglobin (P = .01), higher white blood cell count (P = .03) and percentage blood blasts (P = .03), and a shorter overall survival (P = .08) than WT1 wild-type (WT1wt) patients. Comparing older and younger WT1mut patients, they had similar pretreatment characteristics and outcome. By contrast, among WT1wt CN-AML, younger patients had a significantly better outcome. A WT1 mutation-associated gene-expression signature, reported here for the first time, included CD96, a leukemia stem cell-specific marker, and genes involved in gene regulation (eg, MLL, PML, and SNRPN) and in proliferative and metabolic processes (eg, INSR, IRS2, and PRKAA1), supporting the role of mutated WT1 in deregulating multiple homeostatic processes. Our results indicate that WT1mut CN-AML represents a distinct entity with poor treatment response across age groups. This study has been registered at www.clinicaltrials.gov as #NCT00900224.
Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals
Authors: Quesada Víctor , Velasco Gloria , Puente Xose S , Warren Wesley C , López-Otín Carlos
Published: May 2010

Background

The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch.

Results

A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.

Conclusions

We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.
Carbon monoxide-Releasing Molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats
Authors: Wei Yunwei , Chen Ping , de Bruyn Marco , Zhang Weihui , Bremer Edwin , Helfrich Wijnand
Published: May 2010

Background

Hepatic ischemia-reperfusion injury (I/Ri) is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO) by application of so-called CO-releasing molecules (CORMs). Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model.

Methods

Forty male Wistar rats were randomly assigned into four groups (n = 10). Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg), which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration.

Results

A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in nuclear extracts of liver homogenates. Moreover, CORM-2 treatment resulted in reduced serum levels of pro-inflammatory cytokines TNF-α and IL-6 and down-regulation of the adhesion molecule ICAM-1 in the endothelial cells of liver. In line with these findings, CORM-2 treatment reduced the accumulation of neutrophils in the liver upon I/Ri. Similar treatment with an inactive variant of CORM-2 (iCORM-2) did not have any beneficial effect on the extent of liver I/Ri.

Conclusions

CORM-2 treatment at the time of reperfusion had several distinct beneficial effects on severity of hepatic I/Ri that may be of therapeutic value for the prevention of tissue damage as a result of I/Ri during hepatic surgery.