bluuebunny/crossref_metadata_2025 huggingface dataset:
Using ‘‘Dominetrics’’ to Impose Greater Discipline on Performance Rankings
Authors: Beaulier Scott , Elder Robert
Published: May 2010

Importing the methodology of Cherchye and Vermeulen (2006), the authors discuss the many ways ‘‘dominetrics’’ can measure performance. They then apply the approach to National Collegiate Athletic Association (NCAA) Division I men’s basketball rankings. The ordinal approach they take removes some subjectivity from the Rating Percentage Index (RPI). Just as Pareto relationships are obtained without subjective cardinal weighting schemes, the dominance relationships applied here eliminate the subjectivity of cardinal weighting. Because heated debate inevitably ensues after the NCAA Selection Committee’s announcement of at-large invitees to the NCAA tournament, the subjectivity-minimizing dominetric provides a barometer for evaluating the relative qualities of college basketball teams.
Acupuncture as Palliative Therapy for Physical Symptoms and Quality of Life for Advanced Cancer Patients
Authors: Dean-Clower Elizabeth , Doherty-Gilman Anne M. , Keshaviah Aparna , Baker Frank , Kaw Chiewkwei , Weidong Lu  , Manola Judith , Penson Richard T. , Matulonis Ursula A. , Rosenthal David S.
Published: May 2010

Background. Acupuncture is underutilized as an adjunct cancer therapy. The main study objectives were to determine the feasibility of administering acupuncture as palliative therapy to patients with advanced ovarian or breast cancer and to assess the effect on symptoms and quality of life (QOL). Methods. This study was a pilot, single-armed prospective clinical trial for patients with advanced cancer to receive 12 acupuncture sessions over 8 weeks with follow-up at weeks 9 and 12. Ambulatory patients with advanced ovarian or breast cancer were enrolled to receive treatments at an outpatient academic oncology center. Symptom severity was measured before and after each acupuncture session. A composite QOL assessment tool, consisting of validated instruments, was completed at 5 time points. Results. Forty patients enrolled in the study. Twenty-eight patients (70%; 95% confidence interval [CI] = 53%-83%) completed 4 weeks of treatment, and 26 patients (65%; 95% CI = 48%-79%) completed 8 weeks. Eight patients (20%) withdrew before receiving acupuncture, and 6 patients (15%) discontinued treatment early because of disease progression or scheduling demands. Among all 32 assessed patients, there was self-reported improvement immediately post-treatment in anxiety, fatigue, pain, and depression and significant improvement over time for patients with anxiety ( P = .001) and depression ( P = .02). Among patients experiencing baseline symptoms, there was improvement in anxiety ( P = .001), fatigue ( P = .0002), pain ( P = .0002), and depression ( P = .003). QOL measures of pain severity and interference, physical and psychological distress, life satisfaction, and mood states showed improved scores during treatment, with sustained benefit at 12 weeks. Conclusions. This pilot study demonstrates that an 8-week outpatient acupuncture course is feasible for advanced cancer patients and produces a measurable benefit that should be evaluated in controlled trials.
Venous Duplex Scanning for Suspected Deep Vein Thrombosis: Results Before and After Elimination of After-Hours Studies
Authors: Arnaoutakis George J , Pirrucello James , Brooke Benjamin S , Reifsnyder Thomas
Published: May 2010

Objective: A 24-hour venous duplex ultrasound (VDU) for suspected deep vein thrombosis (DVT) imposes significant resource burdens on a hospital. We hypothesize that termination of after-hours services increases empiric therapy without affecting clinical outcomes. Methods: A retrospective review of patients evaluated by the emergency department (ED) for suspected DVT in 2005 and 2007. Demographics, empiric treatment, and complications were compared using propensity scores and multivariate regression models. Results: In 2005 and 2007, 318 and 365 patients, respectively, had VDU after referral by the ED. In all, 49 (16%) tests during 2005 were after-hours, with 31 and 25 acute DVTs in 2005 and 2007, respectively. More patients received empiric treatment in 2007: 51 (14%) vs 26 ([8%]; P = .019) and tended to be more likely to have acute DVT: 7 (28%) vs 3 ([10%]; P = .08). We detected no complications from empiric anticoagulation and no difference in outcome. Estimated annual savings were $11 864. Conclusions: Elimination of around-the-clock VDU can render substantial savings to hospitals without adverse consequence in the management of acute DVT.
Retrograde Superior Mesenteric Artery Stenting for Acute Mesenteric Arterial Thrombosis
Authors: Do Natalie , Wisniewski Paul , Sarmiento Jose , Vo Trung , Aka Paul K. , Hsu Jeffrey H. , Tayyarah Majid
Published: May 2010

Retrograde superior mesenteric artery stenting (ROMS) represents a significant development in the treatment of acute mesenteric ischemia. Compared to traditional surgical mesenteric bypass, ROMS is a less invasive technique that avoids many complications associated with emergent mesenteric bypass. This case report illustrates that retrograde superior mesenteric artery (SMA) stenting is an option for the treatment of acute mesenteric ischemia for patients in extremis.
Late-Term Complication of Endograft Repair for Aortoenteric Fistula
Authors: Lee Burm , Gutherz Neschis David
Published: May 2010

Aortoenteric fistula is a devastating complication of aortic aneurysm repair. Traditional repair carries a high risk of mortality and significant morbidity. While endograft repair can be effective at mitigating the immediate life-threatening bleed, the temptation to consider endograft repair as definitive treatment should be resisted. We present a case of a 72 year old male who developed an aortoenteric fistula four years following surgical repair of a ruptured aortic aneurysm. Four years thereafter the patient developed infection of the graft and required extra-anatomic bypass and excision of the infected graft. Endograft repair of aortoenteric fistula is associated with persistent infection and should be viewed as a temporizing measure. Here we present the case and review the literature regarding the treatment and outcome of this condition.
Colonic Ischemia After Endovascular Exclusion of an Aortoiliac Aneurysm Using an Iliac Branch Device
Authors: Sfyroeras Giorgos S. , Koutsias Stylianos , Karathanos Christos , Stamoulis Konstantinos , Giannoukas Athanassios D.
Published: May 2010

Purpose: To present the first case of colonic ischemia (CI) after endovascular exclusion of an aortoiliac aneurysm using an iliac branch device (IBD). Case report: A 69-year-old male patient with an abdominal aortic and right common iliac artery aneurysm underwent endovascular repair with an IBD. Completion angiography demonstrated good patency in 2 of the 3 main branches of the right internal iliac artery (IIA) whereas the left IIA patency was preserved. Preoperatively, the inferior mesenteric artery (IMA) was patent. Postoperatively, the patient presented moderate CI. He was treated conservatively and discharged 15 days later with recession of the symptoms. Conclusion: Although preservation of bilateral iliac artery patency is considered to diminish the incidence of pelvic ischemia, in case of an exclusion of a patent IMA, collaterals may not be adequate to ensure blood supply to the left colon.
Latent Congenital Defect: Interrupted Aortic Arch in an Adult—Case Report and Literature Review
Authors: Sakellaridis Timothy , Argiriou Mihalis , Panagiotakopoulos Victor , Krassas Athanasios , Argiriou Orestis , Charitos Christos
Published: May 2010

Interrupted aortic arch (IAA) is rare congenital cardiac defect defined as a complete loss of luminal and anatomical continuity between ascending and descending segments of the aorta. Usually it is detected in the perinatal period or during the first hours or days of infancy. If not treated surgically, it usually is lethal. Nevertheless, diagnosis can be made in adults but is a very rare entity. Extremely few cases in adults are reported in the pertinent medical literature. We present an asymptomatic 62-year-old patient who was found to have IAA after examination for hypertension. The patient underwent a successful anatomical repair, with an uneventful postoperative course, and follow-up examinations reveal regression of hypertension and excellent health condition.
Retrograde Open Mesenteric Stenting for Acute Mesenteric Ischemia is a Viable Alternative for Emergent Revascularization
Authors: Stout Christopher L. , Messerschmidt Cory A. , Leake Andrew E. , Veale William N. , Stokes Gordon K. , Panneton Jean M.
Published: May 2010

Objectives: Significant comorbidities and an exhausted physiologic reserve lead to high mortality rates during operations for acute mesenteric ischemia. We present our experience with retrograde open mesenteric stenting. Methods/Results: A total of 3 female patients (mean age = 74.1 years) with acute mesenteric ischemia underwent exploratory laparotomy. Operative technique included isolating the superior mesenteric artery for cannulation and retrograde endovascular angioplasty and stenting. One required small bowel resection. All 3 patients survived. Mean follow-up was 8.4 months (range: 1.2-16.6). All remain with a 100% primary patency rate. Conclusion: Retrograde open mesenteric stenting for acute mesenteric ischemia is a viable alternative to bypass.
Endovascular Treatment in Postthrombotic Syndrome
Authors: Wahlgren Carl-Magnus , Wahlberg Eric , Olofsson Pär
Published: May 2010

Background: The postthrombotic syndrome is a chronic complication of deep venous thrombosis that leads to considerable pain and suffering to patients. We evaluated our experience of endovascular treatment for patients with chronic postthrombotic femoroiliocaval venous disease. Materials and Methods: From January 2003 through December 2007, 50 patients (51 limbs; 60% women; mean age 45 years; range: 24-74 years) with chronic postthrombotic venous disease were referred to our institution for interventional assessment. All patients underwent duplex ultrasonography as well as ascending and descending venography. The CEAP (clinical, etiologic, anatomic, and pathophysiologic classification) clinical scores were class 0 (no signs) in 2% of limbs, class 3 (edema) in 63%, class 4a (pigmentation or eczema) in 18%, class 5 (healed venous ulcer) in 14%, and class 6 (active venous ulcer) in 4%. The etiology was secondary (postthrombotic) in all patients. The anatomical distribution of reflux and obstruction were deep veins in 63% and a combination of deep and superficial veins in 37%. The underlying pathophysiology due to obstruction of the deep venous outflow with no reflux was found in 25% of limbs, only reflux was found in 14%, and a combination of obstruction and reflux was found in 61%. Results: There were 21 limbs in 20 (38%) patients that underwent endovascular and/or surgical treatment. One limb underwent femoral endovenectomy and 1 limb superficial femoral vein to deep femoral vein transposition. In all, 19 limbs were scheduled for endovascular treatment. The technical success rate was 84%, 3 limbs with iliac vein occlusions could not be recanalized. A total of 11 patients (11 limbs) underwent solely endovascular intervention and 4 patients (5 limbs) underwent endovascular intervention combined with femoral endovenectomy. The endovascular and surgical procedures were performed with no perioperative or postoperative mortality as well as no major bleeding or cardiac, pulmonary, or renal 30-day complications. Early thrombosis (<30 days) of the stented iliac veins occurred in 3 limbs which were lysed and restented successfully. The mean follow-up time was 23 months (range: 1-69 months). Primary and assisted-primary/secondary patency rates at 12 months were 61% and 81%, respectively. The Venous Clinical Severity score was 9.1 (range: 5-15) before endovascular treatment and 6.0 (range: 3-13) after the treatment (P < .0001). There were 30 patients (62%) with symptoms attributable to venous dysfunction or with deep venous pathology that did not undergo interventional treatment after workup. These patients continued with appropriate thromboprophylaxis and elastic compression stockings. Conclusion: Endovascular treatment of chronic postthrombotic femoroiliocaval venous disease is a safe technique that can be performed with acceptable patency rates in this challenging patient population.
Remote Ischemic Preconditioning for Renal Protection During Elective Open Infrarenal Abdominal Aortic Aneurysm Repair: Randomized Controlled Trial
Authors: Walsh Stewart R. , Sadat Umar , Boyle Jonathan R. , Tang Tjun Y. , Lapsley Marta , Norden Anthony G. , Gaunt Michael E.
Published: May 2010

We aimed to determine whether remote ischemic preconditioning (IP) reduces renal damage following elective open infrarenal abdominal aortic aneurysm (AAA) repair. Sequential common iliac clamping was used to induce remote IP in randomized patients. Urinary retinol binding protein (RBP) and albumin-creatinine ratio (ACR) were measured following induction and 3, 24, and 48 hours postoperatively. In controls (n = 22), median urinary RBP increased from 112 µg/mL (interquartile range [IQR] 96-173 µg/mL) preoperatively to 5919 µg/mL (IQR 283-17 788 µg/mL) at 3 hours. Preoperative urinary RBP in preconditioned patients was 96 µg/mL (IQR 50 to 229 µg/mL) preoperatively, rising to 1243 µg/mL (IQR 540 to 15400 µg/mL) at 3 hours. Although control patients’ median urinary RBP level was 5 times greater at 3 hours, there were no statistically significant differences in renal outcome indices. This trial could not confirm that remote IP reduces renal injury following elective open aneurysm surgery.
Developing Diverse, Collaborative Leaders: An Empirical Program Evaluation
Authors: Leigh Jennifer M. , Shapiro Ester R. , Penney Sherry H.
Published: May 2010

Recent work in leadership studies emphasizes the importance of developing leaders who can foster collaboration within diverse workgroups. However, leadership development programs are rarely evaluated using measures that link (a) the program’s theoretical framework, (b) its pedagogical practice, and (c) participants’ changes in specific relevant domains, in comparison to those of a peer group. This study used a quasi-experimental design to empirically evaluate the University of Massachusetts at Boston’s Emerging Leaders Program for its impact on diverse participants coming from corporate and nonprofit sectors in Greater Boston.The program promoted collaborative and inclusive leadership practices among diverse leaders, conceptualized and operationalized using Kouzes and Posner’s Leadership Practices Inventory with instructional methods based in an action learning model. In comparison to a control group, program participants reported greater changes in the frequency of their collaborative leadership behaviors. A critical incident in the program is described using participant observation to illustrate how the program’s reflection-in-action pedagogy promoted collaborative learning in addressing diversity. Implications for research and practice are discussed.
Mediating Role of Creative Identity in the Influence of Transformational Leadership on Creativity: Is There a Multilevel Effect?
Authors: Peng Wang  , Weichun Zhu
Published: May 2010

In this study, the authors examined the relationships among transformational leadership, creative identity, and creativity from a multilevel perspective. They found that individual-level transformational leadership positively affected employees’ individual creativity indirectly through individual creative identity. Group creative identity instead mediated the relationship between group-level transformational leadership and group creativity. In addition, group creative identity mediated the relationship between group-level transformational leadership and individual creative identity. Theoretical and practical implications are discussed.
Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support
Authors: Free Caroline , Hoile Elizabeth , Robertson Steven , Knight Rosemary
Published: May 2010

Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial.

Purpose To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending £5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants.

Methods Single blind controlled trials with allocation concealment. Interventions: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with £5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures.

Results Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6—4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference —0.2 (95% CI —0.6—0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4—6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7—5.2).

Limitations There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic.

Conclusion Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a £5 reimbursement for participants’ time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265—273. http://ctj.sagepub.com
What Happened to Self-Actualization?
Authors: Peterson Christopher , Park Nansook
Published: May 2010

Abraham Maslow’s hierarchy of needs is one of psychology’s genuinely good ideas and has had a sustained impact in and out of psychology. The revision of the hierarchy by Kenrick, Griskevicius, Neuberg, and Schaller (2010 , this issue) is overdue and makes an important contribution by grounding the hierarchy in modern evolutionary thought. However, we suggest that it may be premature to remove self-actualization from the hierarchy by reducing it to other needs associated with status and reproduction.
Ann Saunders: A Bibliography
Authors: Poppy Pat
Published: May 2010

The following bibliography is arranged by date, starting with Ann's publications as Ann Cox-Johnson, and continuing after her marriage as Ann Saunders.
Richard Whittington and His Sales to the Great Wardrobe in the Years 1392 to 1394
Authors: Staniland Kay
Published: May 2010

The list of goods supplied to the Great Wardrobe by Richard Whittington provides a starting point for a better understanding of the early career of this famous merchant of medieval London, one who made his initial fortune by selling large quantities of fine mercery to Richard II and the aristocracy. It demonstrates the range of textiles a medieval mercer like Whittington dealt in, shows how — in the absence of supporting documentation — these may have been used within the royal household, and prompts a consideration of the increased royal spending which has branded the king as extravagant.
An Enigmatic Bourgeois: Jean Revel Dons a Nightgown for His Portrait
Authors: Miller Lesley Ellis
Published: May 2010

This article focuses on the only surviving portrait of Jean Revel (1684–1751), the most eminent French silk designer of the first half of the eighteenth century. It investigates the message created by the artist and the sitter through the dress depicted, setting it firmly within its cultural and social context.
Bespoke Versus Ready-Made: The Work of the Tailor in Eighteenth-Century Britain
Authors: Lambert Miles
Published: May 2010

By the beginning of the eighteenth century, tailors had, for centuries, made bespoke clothing in wool for men, and outer garments for women. As the century developed, a number of tailors drew on a range of commercial opportunities and strengthening popular consumption to expand their businesses and increase their profits. The most dramatic development saw some tailoring establishments offering ready-made garments alongside bespoke, whilst other large-scale 'wholesale tailors' specialized exclusively in made-up clothing. This paper will briefly explore some of the evidence to suggest that tailors turned to the ready-made market during the eighteenth century.
The Versailles Sash
Authors: Ehrman Edwina
Published: May 2010

An object-based analysis of a silk sash printed with neoclassical medallions and several inscriptions, dated 1788 and manufactured by Clay & Hunt, a Coventry ribbon weavers with premises in London.
The Arrival of the Country Relations: Alexander Carse's Painting of 1812
Authors: Tarrant Naomi E. A.
Published: May 2010

The dress in this Scottish painting is discussed in the light of rural and city life styles of the period. This paper is published as a mark of respect for, and appreciation of, Ann Saunders, a friend and colleague within the Society for many years.
Margot Fonteyn and Fashion Designers in the 1940s
Authors: Harden Rosemary
Published: May 2010

This paper examines the role that ballerina Dame Margot Fonteyn played as an advocate for British fashion in the 1940s, with particular reference to the Sadler's Wells tour of the USA after the Second World War. The article draws on surviving ensembles from Dame Margot's wardrobe in the collection at the Fashion Museum (formerly the Museum of Costume) in Bath as well as material in the Theatre Museum Archive in London.
c-Myb, Menin, GATA-3, and MLL form a dynamic transcription complex that plays a pivotal role in human T helper type 2 cell development
Authors: Nakata Yuji , Brignier Anne C. , Jin Shenghao , Shen Yuan , Rudnick Stephen I. , Sugita Mayumi , Gewirtz Alan M.
Published: May 2010

GATA-3 and c-Myb are core elements of a transcriptionally active complex essential for human Th2 cell development and maintenance. We report herein mechanistic details concerning the role of these transcription factors in human peripheral blood Th2 cell development. Silencing c-Myb in normal human naive CD4+ cells under Th2 cell-promoting conditions blocked up-regulation of GATA-3 and interleukin-4, and in effector/memory CD4+ T cells, decreased expression of GATA-3 and Th2 cytokines. In primary T cells, c-Myb allows GATA-3 to autoactivate its own expression, an event that requires the direct interaction of c-Myb and GATA-3 on their respective binding sites in promoter of GATA-3. Immunoprecipitation revealed that the c-Myb/GATA-3 complex contained Menin and mixed lineage leukemia (MLL). MLL recruitment into the c-Myb-GATA-3-Menin complex was associated with the formation Th2 memory cells. That MLL-driven epigenetic changes were mechanistically important for this transition was suggested by the fact that silencing c-Myb significantly decreased the methylation of histone H3K4 and the acetylation of histone H3K9 at the GATA-3 locus in developing Th2 and CD4+ effector/memory cells. Therefore, c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression and, with the recruitment of MLL, Th2 cell maturation in primary human peripheral blood T cells.
Lineage-specific T-cell reconstitution following in vivo CD4+ and CD8+ lymphocyte depletion in nonhuman primates
Authors: Engram Jessica C. , Cervasi Barbara , Borghans Jose A. M. , Klatt Nichole R. , Gordon Shari N. , Chahroudi Ann , Else James G. , Mittler Robert S. , Sodora Donald L. , de Boer Rob J. , Brenchley Jason M. , Silvestri Guido , Paiardini Mirko
Published: May 2010

Many features of T-cell homeostasis in primates are still unclear, thus limiting our understanding of AIDS pathogenesis, in which T-cell homeostasis is lost. Here, we performed experiments of in vivo CD4+ or CD8+ lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (RMs) and sooty mangabeys (SMs). Whereas RMs develop AIDS after infection with simian immunodeficiency virus (SIV), SIV-infected SMs are typically AIDS-resistant. We found that, in both species, most CD4+ or CD8+ T cells in blood and lymph nodes were depleted after treatment with their respective antibodies. These CD4+ and CD8+ lymphocyte depletions were followed by a largely lineage-specific CD4+ and CD8+ T-cell proliferation, involving mainly memory T cells, which correlated with interleukin-7 plasma levels. Interestingly, SMs showed a faster repopulation of naive CD4+ T cells than RMs. In addition, in both species CD8+ T-cell repopulation was faster than that of CD4+ T cells, with CD8+ T cells reconstituting a normal pool within 60 days and CD4+ T cells remaining below baseline levels up to day 180 after depletion. While this study revealed subtle differences in CD4+ T-cell repopulation in an AIDS-sensitive versus an AIDS-resistant species, such differences may have particular relevance in the presence of active SIV repli cation, where CD4+ T-cell destruction is chronic.
Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel
Authors: Yi Hee , Cho Hee-Jung , Cho Soo-Min , Lee Dong-Goo , Abd El-Aty AM , Yoon So-Jeong , Bae Gun-Won , Nho Kwang , Kim Bokyung , Lee Chi-Ho , Kim Jin-Suk , Bartlett Michael G , Shin Ho-Chul
Published: May 2010

Background

We have studied the in vitro and in vivo utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system.

Methods

A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 × 106. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study.

Results

In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group.

Conclusion

We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.
Estrogen regulation of TRPM8 expression in breast cancer cells
Authors: Chodon Dechen , Guilbert Arnaud , Dhennin-Duthille Isabelle , Gautier Mathieu , Telliez Marie-Sophie , Sevestre Henri , Ouadid-Ahidouch Halima
Published: May 2010

Background

The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer.

Methods

RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques.

Results

TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E2, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER+) status of the tumours.

Conclusion

Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.
Traumatic vertebral artery dissection presenting with incomplete congruous homonymous quadrantanopia
Authors: Matti Albert I , Lee Andrew W , Chen Celia S
Published: May 2010

Background

To describe a rare presentation of vertebral artery dissection (VAD) as a small but congruous incomplete homonymous hemianopia demonstrating use of visual field testing in the diagnosis.

Case presentation

A 30 year old woman had been unwell for 4 months with difficulty focusing, vertigo, dizziness and a feeling of falling to the right. A small but congruous right inferior homonymous quadrantanopia was found on examination leading to further investigation that uncovered a vertebral artery dissection and multiple posterior circulation infarctions including a left occipital stroke matching the field defect.

Conclusions

We describe an atypical case of VAD presenting with a small congruous quadrantanopia. This is a rare but significant condition that predisposes to multiple thromboembolic infarction that may be easily misdiagnosed and a high index of suspicion is required to make the diagnosis.
Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats
Authors: Lu Xiao , Guo Xiaomei , Karathanasis Sotirios K , Zimmerman Karen M , Onyia Jude E , Peterson Richard G , Kassab Ghassan S
Published: May 2010

Objectives

Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF) rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi) on endothelial function and mechanical remodeling.

Methods

The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using anex-vivoisovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS), α-adrenoceptor, matrix metalloproteinase 9 (MMP9), and elastase were evaluated.

Results

Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats.

Conclusion

The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.
Glutathione deficiency down-regulates hepatic lipogenesis in rats
Authors: Brandsch Corinna , Schmidt Tobias , Behn Diana , Weiße Kristin , Mueller Andreas S , Stangl Gabriele I
Published: May 2010

Background

Oxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed to investigate the role of glutathione in the regulation of this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase, for 7 days and compared with untreated control rats.

Results

BSO treatment caused a significant reduction of total glutathione in liver (-70%), which was attributable to diminished levels of reduced glutathione (GSH, -71%). Glutathione-deficient rats had lower triglyceride concentrations in their livers than the control rats (-23%), whereas the circulating triglycerides and the cholesterol concentrations in plasma and liver were not different between the two groups of rats. Livers of glutathione-deficient rats had lower mRNA abundance of sterol regulatory element-binding protein (SREBP)-1c (-47%), Spot (S)14 (-29%) and diacylglycerol acyltransferase 2 (DGAT-2, -27%) and a lower enzyme activity of fatty acid synthase (FAS, -26%) than livers of the control rats. Glutathione-deficient rats had also a lower hepatic activity of the redox-sensitive protein-tyrosine phosphatase (PTP)1B, and a higher concentration of irreversible oxidized PTP1B than control rats. No differences were observed in protein expression of total PTP1B and the mature mRNA encoding active XBP1s, a key regulator of unfolded protein and ER stress response.

Conclusion

This study shows that glutathione deficiency lowers hepatic triglyceride concentrations via influencing lipogenesis. The reduced activity of PTP1B and the higher concentration of irreversible oxidized PTP1B could be, at least in part, responsible for this effect.
Validation of the "World Health Organization Disability Assessment Schedule, WHODAS-2" in patients with chronic diseases
Authors: Garin Olatz , Ayuso-Mateos Jose Luis , Almansa Josué , Nieto Marta , Chatterji Somnath , Vilagut Gemma , Alonso Jordi , Cieza Alarcos , Svetskova Olga , Burger Helena , Racca Vittorio , Francescutti Carlo , Vieta Eduard , Kostanjsek Nenad , Raggi Alberto , Leonardi Matilde , Ferrer Montse ,   the MHADIE consortium
Published: May 2010

Background

The WHODAS-2 is a disability assessment instrument based on the conceptual framework of the International Classification of Functioning, Disability, and Health (ICF). It provides a global measure of disability and 7 domain-specific scores. The aim of this study was to assess WHODAS-2 conceptual model and metric properties in a set of chronic and prevalent clinical conditions accounting for a wide scope of disability in Europe.

Methods

1,119 patients with one of 13 chronic conditions were recruited in 7 European centres. Participants were clinically evaluated and administered the WHODAS-2 and the SF-36 at baseline, 6 weeks and 3 months of follow-up. The latent structure was explored and confirmed by factor analysis (FA). Reliability was assessed in terms of internal consistency (Cronbach's alpha) and reproducibility (intra-class correlation coefficients, ICC). Construct validity was evaluated by correlating the WHODAS-2 and SF-36 domains, and comparing known groups based on the clinical-severity and work status. Effect size (ES) coefficient was used to assess responsiveness. To assess reproducibility and responsiveness, subsamples of stable (at 6 weeks) and improved (after 3 moths) patients were defined, respectively, according to changes in their clinical-severity.

Results

The satisfactory FA goodness of fit indexes confirmed a second order factor structure with 7 dimensions, and a global score for the WHODAS-2. Cronbach's alpha ranged from 0.77 (self care) to 0.98 (life activities: work or school), and the ICC was lower, but achieved the recommended standard of 0.7 for four domains. Correlations between global WHODAS-2 score and the different domains of the SF-36 ranged from -0.29 to -0.65. Most of the WHODAS-2 scores showed statistically significant differences among clinical-severity groups for all pathologies, and between working patients and those not working due to ill health (p < 0.001). Among the subsample of patients who had improved, responsiveness coefficients were small to moderate (ES = 0.3-0.7), but higher than those of the SF-36.

Conclusions

The latent structure originally designed by WHODAS-2 developers has been confirmed for the first time, and it has shown good metric properties in clinic and rehabilitation samples. Therefore, considerable support is provided to the WHODAS-2 utilization as an international instrument to measure disability based on the ICF model.
The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells
Authors: Zheng Yihu , Zhou Mengtao , Ye Aifang , Li Qiu , Bai Yongheng , Zhang Qiyu
Published: May 2010

Background

Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. The precise mechanisms of action of arsenic trioxide have though not been elucidated. As the role of Bcl-2 in arsenic trioxide-mediated cell apoptosis and conformation change of Bcl-2 in response to arsenic trioxide treatment has not been studied. The aim of the present study was to determine whether conformation change of Bcl-2 is involved in the action of arsenic trioxide.

Methods

Human gastric cancer SGC7901 cells were exposed to different concentrations of arsenic trioxide. Proliferation was measured by using the Kit-8 cell counting assay. Analysis of nuclear morphology was observed by DAPI staining. The apoptosis rates of cells treated with arsenic trioxide were analyzed by flow cytometry using Annexin V-FITC staining. The conformation change of Bcl-2 and Bax activation were detected by immunostaining and Western blot analysis. Total expression of Bcl-2 and Bax were examined by Western blot analysis.

Results

Arsenic trioxide inhibited the growth of human gastric cancer SGC7901 cells and induced apoptosis. There were two Bcl-2 phenotypes coexisting in SGC7901 cells and the Bcl-2 cytoprotective phenotype could change into a cytodestructive phenotype following conformational change of Bcl-2, triggered by arsenic trioxide exposure. Bax activation might also be involved in arsenic trioxide-induced Bcl-2 conformational change. Arsenic trioxide did not change levels of total Bcl-2 expression, but up-regulated total Bax expression for the treatment time ranging from 3 to 24 hours.

Conclusion

Arsenic trioxide induces apoptosis through induction of Bcl-2 conformational change, Bax activation and up-regulation of total Bax expression rather than affecting total Bcl-2 expression in human gastric cancer SGC7901 cells. The conformational change of Bcl-2 may be a novel described mechanism of arsenic trioxide-induced apoptosis in cancer cells.
Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village
Authors: van der Loeff Maarten F Schim , Larke Natasha , Kaye Steve , Berry Neil , Ariyoshi Koya , Alabi Abraham , van Tienen Carla , Leligdowicz Aleksandra , Sarge-Njie Ramu , da Silva Zacharias , Jaye Assan , Ricard Dominique , Vincent Tim , Jones Sarah Rowland , Aaby Peter , Jaffar Shabbar , Whittle Hilton
Published: May 2010

Background

There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects.

Methods

133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load.

Results

Median age (interquartile range [IQR]) of HIV-2 infected subjects at time of enrollment was 47 (36, 60) years, similar to that of HIV-uninfected control subjects, 49 (38, 62) (p = 0.4). Median (IQR) plasma viral load and CD4 percentage were 347 (50, 4,300) copies/ml and 29 (22, 35) respectively.

Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8%) and 16 (10.1%) of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI) was 4.5 (3.6, 5.8) among HIV-2 infected subjects compared to 2.1 (1.6, 2.9) among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p < 0.001) representing a 2-fold excess mortality rate associated with HIV-2 infection.

Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml) (IQR) did not change significantly over time, being 150 (50, 1,554; n = 77) in 1996, 203 (50, 2,837; n = 47) in 2003 and 171 (50, 497; n = 31) in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia (<100 copies/ml) at baseline: strikingly, mortality in this group was similar to that of the general population.

Conclusions

A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37%) at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given the number of individuals who could not be re-examined.
Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report
Authors: Oertelt-Prigione Sabine , Crosignani Andrea , Gallieni Maurizio , Vassallo Emanuela , Podda Mauro , Zuin Massimo
Published: May 2010

Introduction

A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension.

Case presentation

We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy.

Conclusion

We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.
The role of small non-coding RNAs in genome stability and chromatin organization
Authors: van Wolfswinkel Josien C. , Ketting René F.
Published: May 2010

Small non-coding RNAs make up much of the RNA content of a cell and have the potential to regulate gene expression on many different levels. Initial discoveries in the 1990s and early 21st century focused on determining mechanisms of post-transcriptional regulation mediated by small-interfering RNAs (siRNAs) and microRNAs (miRNAs). More recent research, however, has identified new classes of RNAs and new regulatory mechanisms, expanding the known regulatory potential of small non-coding RNAs to encompass chromatin regulation. In this Commentary, we provide an overview of these chromatin-related mechanisms and speculate on the extent to which they are conserved among eukaryotes.
TRPV1 acts as a synaptic protein and regulates vesicle recycling
Authors: Goswami Chandan , Rademacher Nils , Smalla Karl-Heinz , Kalscheuer Vera , Ropers Hans-Hilger , Gundelfinger Eckart D. , Hucho Tim
Published: May 2010

Electrophysiological studies demonstrate that transient receptor potential vanilloid subtype 1 (TRPV1) is involved in neuronal transmission. Although it is expressed in the peripheral as well as the central nervous system, the questions remain whether TRPV1 is present in synaptic structures and whether it is involved in synaptic processes. In the present study we gathered evidence that TRPV1 can be detected in spines of cortical neurons, that it colocalizes with both pre- and postsynaptic proteins, and that it regulates spine morphology. Moreover, TRPV1 is also present in biochemically prepared synaptosomes endogenously. In F11 cells, a cell line derived from dorsal-root-ganglion neurons, TRPV1 is enriched in the tips of elongated filopodia and also at sites of cell-cell contact. In addition, we also detected TRPV1 in synaptic transport vesicles, and in transport packets within filopodia and neurites. Using FM4-64 dye, we demonstrate that recycling and/or fusion of these vesicles can be rapidly modulated by TRPV1 activation, leading to rapid reorganization of filopodial structure. These data suggest that TRPV1 is involved in processes such as neuronal network formation, synapse modulation and release of synaptic transmitters.
The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity
Authors: Cheng You-Liang , Chen Rey-Huei
Published: May 2010

The assembly, disassembly and dynamic movement of macromolecules are integral to cell physiology. The ubiquitin-selective chaperone Cdc48 (p97 in Metazoa), an AAA-ATPase, might facilitate such processes in the cell cycle. Cdc48 in budding yeast was initially isolated from a mitotic mutant. However, its function in mitosis remained elusive. Here we show that the temperature-sensitive cdc48-3 mutant and depletion of cofactor Shp1 (p47 in Metazoa) cause cell-cycle arrest at metaphase. The arrest is due to a defect in bipolar attachment of the kinetochore that activates the spindle checkpoint. Furthermore, Cdc48-Shp1 positively regulates Glc7/protein phosphatase 1 by facilitating nuclear localization of Glc7, whereas it opposes Ipl1/Aurora B kinase activity. Thus, we propose that Cdc48-Shp1 promotes nuclear accumulation of Glc7 to counteract Ipl1 activity. Our results identify Cdc48 and Shp1 as critical components that balance the kinase and phosphatase activities at the kinetochore in order to achieve stable bipolar attachment.