bluuebunny/crossref_metadata_2025 huggingface dataset:
SCF
Authors: Aggarwal Vikas , Stitt Greg , George Alan , Yoon Changil
Published: June 2012

Heterogeneous computing systems comprised of accelerators such as FPGAs, GPUs, and manycore processors coupled with standard microprocessors are becoming an increasingly popular solution for future computing systems due to their higher performance and energy efficiency. Although programming languages and tools are evolving to simplify device-level design, programming such systems is still difficult and time-consuming largely due to system-wide challenges involving communication between heterogeneous devices, which currently require ad hoc solutions. Most communication frameworks and APIs which have dominated parallel application development for decades were developed for homogeneous systems, and hence cannot be directly employed for hybrid systems. To solve this problem, this article presents the System Coordination Framework (SCF), which employs message passing to transparently enable communication between tasks described using different programming tools (and languages), and running on heterogeneous processing devices of systems from domains ranging from embedded systems to High-Performance Computing (HPC) systems. By hiding low-level architectural details of the underlying communication from an application designer, SCF can improve application development productivity, provide higher levels of application portability, and offer rapid design-space exploration of different task/device mappings. In addition, SCF enables custom communication synthesis that exploits mechanisms specific to different devices and platforms, which can provide performance improvements over generic solutions employed previously. Our results indicate a performance improvement of 28× and 682× by employing FPGA devices for two applications presented in this article, while simultaneously improving the developer productivity by approximately 2.5 to 5 times by using SCF.
Dynamic Defragmentation of Reconfigurable Devices
Authors: Fekete Sándor P. , Kamphans Tom , Schweer Nils , Tessars Christopher , van der Veen Jan C. , Angermeier Josef , Koch Dirk , Teich Jürgen
Published: June 2012

We propose a new method for defragmenting the module layout of a reconfigurable device, enabled by a novel approach for dealing with communication needs between relocated modules and with inhomogeneities found in commonly used FPGAs. Our method is based on dynamic relocation of module positions during runtime, with only very little reconfiguration overhead; the objective is to maximize the length of contiguous free space that is available for new modules. We describe a number of algorithmic aspects of good defragmentation, and present an optimization method based on tabu search. Experimental results indicate that we can improve the quality of module layout by roughly 50% over the static layout. Among other benefits, this improvement avoids unnecessary rejections of modules.
Statistical Timing and Power Optimization of Architecture and Device for FPGAs
Authors: Cheng Lerong , Xu Wenyao , Gong Fang , Lin Yan , Wong Ho-Yan , He Lei
Published: June 2012

Process variation in nanometer technology is becoming an important issue for cutting-edge FPGAs with a multimillion gate capacity. Considering both die-to-die and within-die variations in effective channel length, threshold voltage, and gate oxide thickness, we first develop closed-form models of chip-level FPGA leakage and timing variations. Experiments show that the mean and standard deviation computed by our models are within 3% from those computed by Monte Carlo simulation. We also observe that the leakage and timing variations can be up to 3X and 1.9X, respectively. We then derive analytical yield models considering both leakage and timing variations, and use such models to evaluate the performance of FPGA device and architecture considering process variations. Compared to the baseline, which uses the VPR architecture and device setup based on the ITRS roadmap, device and architecture tuning improves leakage yield by 10.4%, timing yield by 5.7%, and leakage and timing combined yield by 9.4%. We also observe that LUT size of 4 gives the highest leakage yield, LUT size of 7 gives the highest timing yield, but LUT size of 5 achieves the maximum leakage and timing combined yield. To the best of our knowledge, this is the first in-depth study on FPGA architecture and device coevaluation considering process variation.
Automatic inference of memory fences
Authors: Kuperstein Michael , Vechev Martin , Yahav Eran
Published: June 2012

We addresses the problem of automatic verification and fence inference in concurrent programs running under relaxed memory models. Modern architectures implement relaxed memory models in which memory operations may be reordered and executed non-atomically. Instructions called
memory fences
are provided to the programmer, allowing control of this behavior. To ensure correctness of many algorithms, the programmer is often required to explicitly insert memory fences into her program. However, she must use as few fences as possible, or the benefits of the relaxed architecture may be lost. It is our goal to help automate the fence insertion process.

We present an algorithm for automatic inference of memory fences in concurrent programs, relieving the programmer from this complex task. Given a finite-state program, a safety specification and a description of the memory model our algorithm computes a set of ordering constraints that guarantee the correctness of the program under the memory model. The computed constraints are maximally permissive: removing any constraint from the solution would permit an execution violating the specification. These constraints are then realized as additional fences in the input program.

We implemented our approach in a pair of tools called fender and blender and used them to infer correct and efficient placements of fences for several non-trivial algorithms, including practical mutual exclusion primitives and concurrent data structures.
Gαq/11-mediated intracellular calcium responses to retrograde flow in endothelial cells
Authors: Melchior Benoît , Frangos John A.
Published: June 2012

Disturbed flow patterns, including reversal in flow direction, are key factors in the development of dysfunctional endothelial cells (ECs) and atherosclerotic lesions. An almost immediate response of ECs to fluid shear stress is the increase in cytosolic calcium concentration ([Ca2+]i). Whether the source of [Ca2+]i is extracellular, released from Ca2+ intracellular stores, or both is still undefined, though it is likely dependent on the nature of forces involved. We have previously shown that a change in flow direction (retrograde flow) on a flow-adapted endothelial monolayer induces the remodeling of the cell-cell junction along with a dramatic [Ca2+]i burst compared with cells exposed to unidirectional or orthograde flow. The heterotrimeric G protein-α q and 11 subunit (Gαq/11) is a likely candidate in effecting shear-induced increases in [Ca2+]i since its expression is enriched at the junction and has been previously shown to be activated within seconds after onset of flow. In flow-adapted human ECs, we have investigated to what extent the Gαq/11 pathway mediates calcium dynamics after reversal in flow direction. We observed that the elapsed time to peak [Ca2+]i response to a 10 dyn/cm2 retrograde shear stress was increased by 11 s in cells silenced with small interfering RNA directed against Gαq/11. A similar lag in [Ca2+]i transient was observed after cells were treated with the phospholipase C (PLC)-βγ inhibitor, U-73122, or the phosphatidylinositol-specific PLC inhibitor, edelfosine, compared with controls. Lower levels of inositol 1,4,5-trisphosphate accumulation seconds after the onset of flow correlated with the increased lag in [Ca2+]i responses observed with the different treatments. In addition, inhibition of the inositol 1,4,5-trisphosphate receptor entirely abrogated flow-induced [Ca2+]i. Taken together, our results identify the Gαq/11-PLC pathway as the initial trigger for retrograde flow-induced endoplasmic reticulum calcium store release, thereby offering a novel approach to regulating EC dysfunctions in regions subjected to the reversal of blood flow.
Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C
Authors: Schoultz Ida , McKay Catherine M. , Graepel Rabea , Phan Van C. , Wang Arthur , Söderholm Johan , McKay Derek M.
Published: June 2012

The enteric epithelium must absorb nutrients and water and act as a barrier to the entry of luminal material into the body; this barrier function is a key component of innate immunity. Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy occurs via inhibition of prostaglandin synthesis and perturbed epithelial mitochondrial activity. Here, the direct effect of NSAIDs [indomethacin, piroxicam (cyclooxygenase 1 and 2 inhibitors), and SC-560 (a cyclooxygenase 1 inhibitor)] on the barrier function of human T84 epithelial cell line monolayers was assessed by transepithelial electrical resistance (TER) and internalization and translocation of a commensal Escherichia coli . Exposure to E. coli in the presence and absence of drugs for 16 h reduced TER; however, monolayers cotreated with E. coli and indomethacin, but not piroxicam or SC-560, displayed significant increases in internalization and translocation of the bacteria. This was accompanied by increased reactive oxygen species (ROS) production, which was also increased in epithelia treated with E. coli only. Colocalization revealed upregulation of superoxide synthesis by mitochondria in epithelia treated with E. coli + indomethacin. Addition of antioxidants (vitamin C or a green tea polyphenol, epigallocathechin gallate) quenched the ROS and prevented the increase in E. coli internalization and translocation evoked by indomethacin, but not the drop in TER. Evidence of increased apoptosis was not observed in this model. The data implicate epithelial-derived ROS in indomethacin-induced barrier dysfunction and show that a portion of the bacteria likely cross the epithelium via a transcellular pathway. We speculate that addition of antioxidants as dietary supplements to NSAID treatment regimens would reduce the magnitude of decreased barrier function, specifically the transepithelial passage of bacteria.
Cellular mechanism of mechanotranscription in colonic smooth muscle cells
Authors: Li Feng , Lin You-Min , Sarna Sushil K. , Shi Xuan-Zheng
Published: June 2012

Mechanical stretch in obstruction induces expression of cyclooxygenase-2 (COX-2) in gut smooth muscle cells (SMCs). The stretch-induced COX-2 plays a critical role in motility dysfunction in obstructive bowel disorders (OBDs). The aims of the present study were to investigate the intracellular mechanism of mechanotranscription of COX-2 in colonic SMCs and to determine whether inhibition of mechanotranscription has therapeutic benefits in OBDs. Static stretch was mimicked in vitro in primary culture of rat colonic circular SMCs (RCCSMCs) and in colonic circular muscle strips. Partial obstruction was surgically induced with a silicon band in the distal colon of rats and COX-2-deficient mice. Static stretch of RCCSMCs significantly induced expression of COX-2 mRNA and protein and activated MAP kinases ERKs, p38, and JNKs. ERKs inhibitor PD98059, p38 inhibitor SB203580, and JNKs inhibitor SP600125 significantly blocked stretch-induced COX-2 expression. Pharmacological and molecular inhibition of stretch-activated ion channels (SACs) and integrins significantly suppressed stretch-induced expression of COX-2. SAC blockers inhibited stretch-activated ERKs, p38, and JNKs, but inhibition of integrins attenuated p38 activation only. In colonic circular muscle strips, stretch led to activation of MAPKs, induction of COX-2, and suppression of contractility. Inhibition of p38 with SB203580 blocked COX-2 expression and restored muscle contractility. Administration of SB203580 in vivo inhibited obstruction-induced COX-2 and improved motility function. Stretch-induced expression of COX-2 in RCCSMCs depends on mechanosensors, SACs, and integrins and an intracellular signaling mechanism involving MAPKs ERKs, p38, and JNKs. Inhibitors of the mechanotranscription pathway have therapeutic potentials for OBDs.
Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell trait
Authors: Vincent Lucile , Oyono-Enguéllé Samuel , Féasson Léonard , Banimbek Viviane , Dohbobga Macias , Martin Cyril , Thiriet Patrice , Francina Alain , Dubouchaud Hervé , Sanchez Hervé , Chapot Rachel , Denis Christian , Geyssant André , Messonnier Laurent
Published: June 2012

To assess the effects of regular physical activity on muscle functional characteristics of carriers of sickle cell trait (SCT), 39 untrained (U) and trained (T) hemoglobin (Hb)AA (CON) and SCT subjects (U-CON, n = 12; U-SCT, n = 8; T-CON, n = 10; and T-SCT, n = 9) performed a graded exercise and a time to exhaustion (Tex) test, and were subjected to a muscle biopsy. Maximal power, total work performed during Tex, citrate synthase and cytochrome c oxidase (COX) activities, respiratory chain complexes I and IV content, and capillary density (CD), diameter (COD), and surface area (CSA) were upregulated by the same proportion in T-CON and T-SCT compared with their untrained counterparts. These proportionally similar differences imply that the observed discrepancies between U-SCT and U-CON remained in the trained subjects. Specifically, both CD and COX remained and tended to remain lower, and both COD and CSA remained and tended to remain higher in T-SCT than in T-CON. Besides, carriers of SCT displayed specific adaptations with regular physical activity: creatine kinase activity; complexes II, III, and V content; and type I fiber surface area and capillary tortuosity were lower or unchanged in T-SCT than in U-SCT. In summary, our results show that 1) carriers of SCT adapted almost similarly to CON to regular physical activity for most of the studied muscle characteristics, 2) oxidative potential remains altered in physically active carriers of SCT compared with HbAA counterparts, and 3) the specific remodeling of muscle microvascular network persists in the trained state.
Alternate Splicing of the p53 Inhibitor HDMX Offers a Superior Prognostic Biomarker than p53 Mutation in Human Cancer
Authors: Lenos Kristiaan , Grawenda Anna M. , Lodder Kirsten , Kuijjer Marieke L. , Teunisse Amina F.A.S. , Repapi Emmanouela , Grochola Lukasz F. , Bartel Frank , Hogendoorn Pancras C.W. , Wuerl Peter , Taubert Helge , Cleton-Jansen Anne-Marie , Bond Gareth L. , Jochemsen Aart G.
Published: June 2012

Conventional high-grade osteosarcoma is the most common primary bone malignancy. Although altered expression of the p53 inhibitor HDMX (Mdmx/Mdm4) is associated with cancer risk, progression, and outcome in other tumor types, little is known about its role in osteosarcoma. High expression of the Hdmx splice variant HDMX-S relative to the full-length transcript (the HDMX-S/HDMX-FL ratio) correlates with reduced HDMX protein expression, faster progression, and poorer survival in several cancers. Here, we show that the HDMX-S/HDMX-FL ratio positively correlates with less HDMX protein expression, faster metastatic progression, and a trend to worse overall survival in osteosarcomas. We found that the HDMX-S/HDMX-FL ratio associated with common somatic genetic lesions connected with p53 inhibition, such as p53 mutation and HDM2 overexpression in osteosarcoma cell lines. Interestingly, this finding was not limited to osteosarcomas as we observed similar associations in breast cancer and a variety of other cancer cell lines, as well as in tumors from patients with soft tissue sarcoma. The HDMX-S/HDMX-FL ratio better defined patients with sarcoma with worse survival rates than p53 mutational status. We propose a novel role for alternative splicing of HDMX, whereby it serves as a mechanism by which HDMX protein levels are reduced in cancer cells that have already inhibited p53 activity. Alternative splicing of HDMX could, therefore, serve as a more effective biomarker for p53 pathway attenuation in cancers than p53 gene mutation. Cancer Res; 72(16); 4074–84. ©2012 AACR.
Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism
Authors: Karoor Vijaya , Le Mysan , Merrick Daniel , Fagan Karen A. , Dempsey Edward C. , Miller York E.
Published: June 2012

Patients with chronic obstructive pulmonary disease (COPD) are at an increased risk for the development of lung cancer, the mechanisms for which are incompletely understood. We hypothesized that the hypoxic pulmonary microenvironment present in COPD would augment lung carcinogenesis. Mice were subjected to chemical carcinogenesis protocols and placed in either hypoxia or normoxia. Mice exposed to chronic hypoxia developed tumors with increased volume compared with normoxic controls. Both lungs and tumors from hypoxic mice showed a preferential stabilization of HIF-2α and increased expression of VEGF-A, FGF2, and their receptors as well as other survival, proliferation, and angiogenic signaling pathways regulated by HIF-2α. We showed that tumors arising in hypoxic animals have increased sensitivity to VEGFR-2/EGFR inhibition, as chemoprevention with vandetanib showed markedly increased activity in hypoxic mice. These studies showed that lung tumors arising in a hypoxic microenvironment express increased growth, angiogenic, and survival signaling that could contribute to the increased lung cancer risk in COPD. Furthermore, the differential sensitivity of tumors arising in hypoxia to VEGFR-2/EGFR inhibition suggests that the altered signaling present in tumors arising in hypoxic lung might be therapeutically exploited in patients with underlying COPD. Cancer Prev Res; 5(8); 1061–71. ©2012 AACR.
EGFR/TGFα and TGFβ/CTGF Signaling in Neuroendocrine Neoplasia: Theoretical Therapeutic Targets
Authors: Kidd M. , Schimmack S. , Lawrence B. , Alaimo D. , Modlin I.M.
Published: June 2012

Neuroendocrine neoplasms (NENs) are a heterogeneous family of malignancies whose proliferation is partially dependent on growth factors secreted by the microenvironment and the tumor itself. Growth factors which were demonstrated to be important in experimental models of NENs include EGF (epidermal growth factor), TGF (transforming growth factor) α, TGFβ and CTGF (connective tissue growth factor). EGF and TGFα bind to the EGF receptor to stimulate an intact RAS/RAF/MAPK pathway, leading to the transcription of genes associated with cell proliferation, invasion and metastasis. Theoretically, TGFα stimulation can be inhibited at several points of the MAPK pathway, but success is limited to NEN models and is not evident in the clinical setting. TGFβ1 stimulates TGFβ receptors (TGFβRI and TGFβRII) resulting in inhibition of neuroendocrine cell growth through SMAD-mediated activation of the growth inhibitor P21WAF1/CIP1. Although some NENs are inhibited by TGFβ1, paradoxical growth is seen in experimental models of gastric and small intestinal (SI) NENs. Therapeutic targeting of TGFβ1 in NENs is therefore complicated by uncertainty of the effect of TGFβ1 secretion on the direction of proliferative regulation. CTGF expression is associated with more malignant clinical phenotypes in a variety of cancers, including NENs. CTGF promotes growth in gastric and SI-NEN models, and is implicated as a mediator of local and distant fibrosis caused by NENs of enterochromaffin cell origin. CTGF inhibitors are available, but their anti-proliferative effect has not been tested in NENs. In summary, growth factors are essential for NEN proliferation, and although interventions targeting these proteins are effective in experimental models, only limited clinical efficacy has been identified.
An Epidemiologic Survey of Chronic Intestinal Pseudo-Obstruction and Evaluation of the Newly Proposed Diagnostic Criteria
Authors: Ohkubo Hidenori , Iida Hiroshi , Takahashi Hirokazu , Yamada Eiji , Sakai Eiji , Higurashi Takuma , Sekino Yusuke , Endo Hiroki , Sakamoto Yasunari , Inamori Masahiko , Sato Hajime , Fujimoto Kazuma , Nakajima Atsushi
Published: June 2012

Background and Aims: Chronic intestinal pseudo-obstruction (CIPO) is an intractable disease in which clinical symptoms of intestinal obstruction appear without mechanical cause. No clear diagnostic criteria have been established; therefore, we proposed diagnostic criteria to facilitate the diagnosis of this rare disease and aim to evaluate their usefulness and validity. Materials andMethods: A questionnaire was sent to 378 institutions belonging to the Japanese Society of Gastroenterology between December 2009 and February 2010. We summarized the returned data and performed a statistical analysis. Results: A total of 160 cases were included, and 141 cases (88.1%) fulfilled the criterion of disease duration of >6 months, 157 cases (98.1%) the criterion of the clinical symptoms of abdominal pain and/or bloating and 154 cases (96.2%) fulfilled the criterion of imaging findings. Eventually, 138 cases (86.3%) fulfilled all criteria. Conclusions: The proposed diagnostic criteria were useful, with a high sensitivity of 86.3% for Japanese patients. Improved recognition of CIPO and practical use of the criteria are desired. The criteria should be appropriately modified by additional researchers to make them more practical and internationally applicable.
Maternal C-Reactive Protein at Hospital Admission Is a Simple Predictor of Funisitis in Preterm Premature Rupture of Membranes
Authors: Perrone Giuseppina , Anceschi Maurizio M. , Capri Oriana , Galoppi Paola , Pizzulo Sabrina , Buccheri Matteo , Pascone Roberto , Nofroni Italo , Brunelli Roberto
Published: June 2012

Aim: To analyze the prognostic value of maternal serum C-reactive protein (CRP) in predicting funisitis in patients with preterm premature rupture of membranes (pPROM). Methods: 66 patients (gestational age 24–33 weeks) hospitalized 1–12 h after pPROM were enrolled. White blood cell count (WBC), platelet count (PLT) and plasma concentration of CRP were assessed every 3 days. Histological evidence of chorioamnionitis and funisitis was obtained post-partum. Receiver operating characteristic (ROC) curves were employed to evaluate the role of maternal CRP in predicting funisitis. Results: Funisitis was found in 24 patients (36.3%); 42 patients (63.7%) without funisitis were considered as controls. PLT and WBC at admission and before delivery did not show significant differences and were not statistically different between the two groups. Patients with funisitis had significantly higher CRP levels both at admission to hospital and 24– 48 h before delivery. ROC curve analysis showed that CRP at admission (area under the curve: 0.671, p = 0.021) and before delivery (area under the curve: 0.737, p = 0.001) are predictive of funisitis. Conclusions: High maternal serum CRP levels (>20,000 µg/l) in pPROM patients at admission to hospital may be an early marker which indicates, with a good diagnostic performance, the presence of funisitis.
Small Intestinal Edema Had the Strongest Correlation with Portal Venous Pressure amongst Capsule Endoscopy Findings
Authors: Takahashi Yoko , Fujimori Shunji , Narahara Yoshiyuki , Gudis Katya , Ensaka Yukiko , Kosugi Yuki , Maki Kotaro , Suzuki Masahiro , Matsushita Yoko , Fukuda Takeshi , Kanazawa Hidenori , Sakamoto Choitsu
Published: June 2012

Background/Aim: Previous studies have reported small intestinal lesions in patients with portal hypertensive disease. However, the etiology of these lesions is not clear, as portal venous pressure was not measured in any of these studies. The aim of this study is to clarify the association between small intestinal lesions and hepatic venous pressure gradient (HVPG), which correlates well with portal venous pressure. Methods: Thirty-five patients with liver cirrhosis were evaluated by capsule endoscopy for small intestinal lesions. HVPG was measured within 3 days of capsule endoscopy. Blood tests, clinical symptoms, Child-Pugh classification and HVPG were analyzed against small intestinal lesions such as edemas, red spots, angiodysplasia and varices. Lesions were categorized according to their location in the duodenum, jejunum or ileum. Edema was evaluated using a 4-grade capsule endoscopy scoring index. Results: HVPG and edema scores increased with Child-Pugh scores. Red spots and angiodysplasia did not correlate with HVPG. Varices were detected in only 5 patients. The edema score was the factor which most strongly correlated with HVPG by multivariate analysis (p = 0.0008). There was also a strong linear relation between edema scores and HVPG (R = 0.75, p < 0.0001). Conclusion: Small intestinal edemas showed the strongest correlation with HVPG among all small intestinal lesions.
Laboratory Effect on Platelet Activity within 24 h of the First 300-mg Oral Dose of Aspirin Given in Hospital during the Acute Phase of Ischemic Cerebral Events
Authors: Richard S. , Toussaint-Hacquard M. , Fay R. , Lacour J.C. , Ducrocq X. , Lecompte T.
Published: June 2012

Background and Purpose: Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. It inhibits the production of thromboxane (TX) A2, a powerful platelet activator. Despite this protection, early ischemic recurrences are frequent and considered clinical failures of this therapy. Only a few trials have focused on the use of antiplatelet therapy during this phase, and none has described the laboratory effect of the first dose of aspirin given after an ischemic cerebral event. However, this study may help clinicians to understand the mechanisms of early recurrences, and to design new therapeutic strategies, in particular for patients already treated with a daily dose of aspirin. Method: We studied laboratory parameters of the first 300-mg oral dose of aspirin given within 48 h after an ischemic cerebral event. Two blood samples were taken from all of the patients: the first during the third hour following aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary sample was taken before aspirin intake (T0). Platelet reactivity was studied on the basis of serum TXB2 levels, a metabolite of TXA2, and light transmission aggregometry after stimulation of platelet-rich plasma by arachidonic acid and by two concentrations of collagen, i.e. 2 µg/ml (Col2), dependent on the TXA2 pathway, and 20 µg/ml (Col20), independent of the TXA2 pathway. Results with Col2 were related to results with Col20 (Col2/20 ratio) to limit the impact of variations induced by the effects of preanalytical conditions. Results: Fifty patients were included. TXB2 values (p < 0.001) and relative values of the Col2/20 ratio (p = 0.037) were significantly higher at T2 compared to T1. For patients already treated with aspirin, TXB2 levels (p < 0.001) were significantly lower at T1 compared to T0, and the Col2/20 ratio tended to decrease (p = 0.096). Conclusion: Platelet reactivity recovers within 24 h following the first 300-mg oral dose of aspirin during the acute phase of a cerebral ischemic event as demonstrated by an increase in TXB2 levels, and the Col2/20 ratio, at T2 compared to T1. This would favor early ischemic recurrences. However, for patients already treated with aspirin, this dose is able to decrease TXB2 levels and to complete the inhibition of the TXA2 pathway, which shows the utility of this prescription in this case.
Recent Advances in the Study of Age-Related Hearing Loss: A Mini-Review
Authors: Kidd III Ambrose R. , Bao Jianxin
Published: June 2012

Hearing loss is a common age-associated affliction that can result from the loss of hair cells and spiral ganglion neurons (SGNs) in the cochlea. Although hair cells and SGNs are typically lost in the same cochlea, recent analysis suggests that they can occur independently, via unique mechanisms. Research has identified both environmental and genetic factors that contribute to degeneration of cochlear cells. Additionally, molecular analysis has identified multiple cell-signaling mechanisms that likely contribute to pathological changes that result in hearing deficiencies. These analyses should serve as useful primers for future work, including genomic and proteomic analysis, to elucidate the mechanisms driving cell loss in the aging cochlea. Significant progress in this field has occurred in the past decade. As our understanding of aging-induced cochlear changes continues to improve, our ability to offer medical intervention will surely benefit the growing elderly population.
Effect of Intraoperative Amino Acid Infusion on Blood Glucose under General Anesthesia Combined with Epidural Block
Authors: Zhong Jing , Ge Sheng Jin , Zhuang Xiao Feng , Cang Jing , Xue Zhang Gang
Published: June 2012

Aim: To investigate the effect of intraoperative amino acid infusion on blood glucose in patients under general anesthesia combined with epidural block. Methods: 36 patients were randomly assigned to receive an intraoperative infusion of 18 compound amino acids (group AA) or lactated Ringer solution (group LR) at 2 ml·kg–1·h–1. Nasopharyngeal temperature, and blood glucose, plasma insulin, C-peptide and glucagon concentrations were measured 30 min before induction (T0), 10 min after induction (T1), 30 min and 2 h after skin incision (T2, T3), and 30 min and 2 h postoperatively (T4, T5). Results: Nasopharyngeal temperature values, which decreased during surgery in both groups, were significantly higher in group AA than in group LR from T3 to T5. Compared with T0, the blood glucose concentration increased significantly from T2 in group AA and T3 in group LR to T5. Plasma insulin and C-peptide concentrations did not change significantly in group LR, while both increased significantly in group AA from T1 to T4. The plasma glucagon concentration did not change significantly in either group. Conclusion: Intraoperative amino acid infusion in patients under general anesthesia combined with epidural block may accelerate the increase of blood glucose concentration and stimulate insulin secretion, and can alleviate hypothermia during the later period of surgery and postoperatively.
Validation of First Trimester Screening for Trisomy 21 in Singapore with Reference to Performance of Nasal Bone
Authors: Yeo George Seow Heong , Lai Fon-Min , Wei Xing , Lata Padma , Tan Doreen Tsai Hia , Yong Min Hwee , Tan Edward Teck Hoo , Kwek Kenneth Yung Chiang
Published: June 2012

Introduction: The aim of this study is to describe the performance of first trimester screening (FTS) for trisomy 21 using maternal age, serum biochemistry and fetal nuchal translucency (NT) in a single center and to evaluate the effect of nasal bone on screening performance. Material and Methods: In 12,585 singleton pregnancies, the NT and nasal bone were examined. The majority of these mothers also had their serum biochemical markers analyzed. Risk was computed using different combinations of maternal age, biochemistry, NT and nasal bone. Down syndrome cases were confirmed by karyotyping. Results: There were 12,519 normal pregnancies, 31 with trisomy 21 and 35 with other chromosomal abnormalities. Without considering the nasal bone, the combined FTS detected 87.1% of trisomy 21 fetuses (false positive rate 5.1%), using 1:300 as the risk threshold, and this was further improved to 96.8% with the policy that classifies all fetuses with an absent nasal bone as high risk. Subgroup analysis showed that the detection rate would be 90.9%, with a false positive rate of 3.7%, if nasal bone was incorporated in the risk algorithm, compared to 81.8% and a false positive rate of 5.4% if it was not used. Discussion: FTS is very effective in early detection of trisomy 21 in Singapore. The nasal bone is a useful marker that can substantially improve the screening performance.
Retinal Pigment Epithelium Tears in Age-Related Macular Degeneration Treated with Antiangiogenic Drugs: A Controlled Study with Long Follow-Up
Authors: Coco Rosa M. , Sanabria M. Rosa , Hernandez Arturo G. , Fernández Muñoz Marta
Published: June 2012

Purpose: To study whether anti-vascular endothelial growth factor (VEGF) therapy improves visual acuity (VA) in patients with exudative age-related macular degeneration (AMD) complicated with retinal pigment epithelium (RPE) tears. Methods: Retrospective case-control series. Group I (control group) included 9 patients with RPE tears that received no treatment, and group II (intervention group) incorporated 12 patients treated with anti-VEGF. Results: A statistically significant difference was found in VA between the groups from the 3rd month to the final follow-up (p = 0.034). Final VA improved in the treatment group (p = 0.015). No differences were found in central macular thickness between the groups either before or after treatment. Mean number of injections in group II was 5.75 (SD = 1.19). Most patients presented a grade 3 rip. All lesions were inactive at the end of follow-up in group II and 1 remained active in group I. The number of final atrophic/disciform scars was 6/8 in group I and 7/5 in group II. Conclusions: RPE tears treated with antiangiogenic drugs experienced functional benefit. To the authors’ knowledge, this is the first controlled series reporting effectiveness of suppression of neovascular activity with antiangiogenic treatment after RPE rip in AMD.
Refractory Salmonella enterica Serotype choleraesuis-Related Renal Cyst Infection in a Patient with Autosomal Dominant Polycystic Kidney Disease Undergoing Hemodialysis Treated Successfully with Intracystic Ciprofloxacin Infusion
Authors: Yang Chih-Chao , Chuang Feng-Rong , Wu Chien-Hsing , Chen Jin-Bor , Lee Chih-Hsiung , Lee Chien-Te
Published: June 2012

Objective: To report a potential salvage therapy for refractory renal cyst infection secondary to Salmonellaenterica serotype choleraesuis (S. choleraesuis).Clinical Presentation and Intervention: A 52-year-old male with autosomal dominant polycystic kidney disease undergoing hemodialysis experienced an episode of S. choleraesuis-related gastroenteritis subsequently complicated by bloodstream and refractory renal cyst infection with formation of multiple pyocysts. The patient was treated with intracystic indwelling diluted ciprofloxacin solution. Conclusion: In this patient, intracystic infusion of ciprofloxacin achieved a sufficient antibiotic level in infected renal cysts and hence completely eradicated S. choleraesuis. Therefore, intracystic antiobiotic infusion could be a potential salvage therapy for refractory renal cyst infection.
Mineral Ions in the Fluid of Biofilms Formed on Enamel and Dentine Shortly after Sugar Challenge
Authors: Correia M.F. , Tenuta L.M.A. , Del Bel Cury A.A. , Cury J.A.
Published: June 2012

To test the effect of distinct solubilities of dentine and enamel on mineral ion concentration in the biofilm fluid during a sugar-induced pH drop, dental biofilms were formed in situ for 4 days on acrylic (control), dentine or enamel. On the 5th day, they were treated with water (control) or 20% glucose and collected 5 min later. Significantly lower pH values and higher calcium concentrations were found in the biofilm fluid after glucose exposure, without significant differences among the three substrates. During pH drop, biofilm reservoirs release calcium to the fluid, masking the differential solubility between enamel and dentine.
MMP13 Polymorphism Decreases Risk for Dental Caries
Authors: Tannure P.N. , Küchler E.C. , Falagan-Lotsch P. , Amorim L.M.F. , Raggio Luiz R. , Costa M.C. , Vieira A.R. , Granjeiro J.M.
Published: June 2012

Recent evidence suggests that genetic studies may contribute to a better understanding of individual susceptibility to caries. Matrix metalloproteinases (MMPs) and their tissue inhibitors have been suggested to be involved in the caries process. The purpose of this study was to determine if polymorphisms in MMP2 (rs243865), MMP9 (rs17576), MMP13 (rs2252070), and TIMP2 (rs7501477) were associated with caries. Eligible unrelated children and adolescents were evaluated using a cross-sectional design. Data on oral health habits was obtained through a questionnaire and caries data was collected by clinical examination. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between individuals with and without caries experience. Of 505 subjects, 212 were caries-free and most subjects (61.2%) had mixed dentition. Allele frequency of MMP2, MMP13 and TIMP2 was different between caries-affected and caries-free individuals, with significant association for MMP13 (p = 0.004). Mutant allele carriers for MMP13 demonstrated a significantly decreased risk for caries (OR = 0.538, 95% CI 0.313–0.926); this result remained significant after adjustment for candidate genes, type of dentition and dietary factors. Allelic and genotype frequencies of the polymorphism in MMP9 were similar in caries-affected and caries-free individuals. Genetic variations in MMP13 may contribute to individual differences in caries susceptibility. Our findings reinforce that susceptibility to caries results from gene-environment interactions.
Fluorescent Banding Pattern and Species-Specific DNA Marker in Rumex thyrsiflorus Fingerh.
Authors: Grabowska-Joachimiak A. , Kwolek D. , Kula A. , Marciniuk P.
Published: June 2012

The object of this work was to analyze the karyotype structure of Rumex thyrsiflorus using differential fluorescent methods of chromosome staining (C-banding/DAPI and CMA3/DA/DAPI) and molecular sex markers. The results obtained were compared with data on the structure of the sex chromosomes and autosomes in R. acetosa, a model species in studies of sex determination and sex chromosome evolution in plants with an XX/XY1Y2 system. A high level of similarity was found in the sex chromosome structure of the 2 species, along with small differences in their autosomal complexes. It suggests that differentiation of these 2 closely related species was not accompanied by major structural changes within their sex chromosomes. Molecular tests, however, revealed differences in the composition of male-specific repetitive sequence RAYSII, occurring in the Y1 chromosome. Amplification of this sequence showed the presence of a single product (∼700 bp) in R. acetosa and of 2 products (∼600 bp and ∼700 bp) in R. thyrsiflorus. The longer product (∼700 bp) was also revealed in R. arifolius, another species closely related to R. acetosa. The shorter DNA fragment, characteristic of R. thyrsiflorus, differed from the common product by of a large indel with a length of 110 bp. This fragment may serve as a species-specific molecular marker useful in taxonomical and population studies as well as in further research on the sex chromosome differentiation in R. thyrsiflorus.
Endothelial Microparticle Uptake in Target Cells Is Annexin I/Phosphatidylserine Receptor Dependent and Prevents Apoptosis
Authors: Jansen Felix , Yang Xiaoyan , Hoyer Friedrich Felix , Paul Kathrin , Heiermann Nadine , Becher Marc Ulrich , Hussein Nebal Abu , Kebschull Moritz , Bedorf Jörg , Franklin Bernardo S. , Latz Eicke , Nickenig Georg , Werner Nikos
Published: June 2012

Objective—

Endothelial microparticles (EMP) are released from activated or apoptotic cells, but their effect on target cells and the exact way of incorporation are largely unknown. We sought to determine the uptake mechanism and the biological effect of EMP on endothelial and endothelial-regenerating cells.

Methods and Results—

EMP were generated from starved endothelial cells and isolated by ultracentrifugation. Caspase 3 activity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that EMP protect target endothelial cells against apoptosis in a dose-dependent manner. Proteomic analysis was performed to identify molecules contained in EMP, which might be involved in EMP uptake. Expression of annexin I in EMP was found and confirmed by Western blot, whereas the corresponding receptor phosphatidylserine receptor was present on endothelial target cells. Silencing either annexin I on EMP or phosphatidylserine receptor on target cells using small interfering RNA showed that the uptake of EMP by human coronary artery endothelial cells is annexin I/phosphatidylserine receptor dependent. Annexin I–downregulated EMP abrogated the EMP-mediated protection against apoptosis of endothelial target cells. p38 activation was found to mediate camptothecin-induced apoptosis. Finally, human coronary artery endothelial cells pretreated with EMP inhibited camptothecin-induced p38 activation.

Conclusion—

EMP are incorporated by endothelial cells in an annexin I/phosphatidylserine receptor–dependent manner and protect target cells against apoptosis. Inhibition of p38 activity is involved in EMP-mediated protection against apoptosis.
Outcome After Mobilization Within 24 Hours of Acute Stroke
Authors: Sundseth Antje , Thommessen Bente , Rønning Ole Morten
Published: June 2012

Background and Purpose—

Very early mobilization (VEM) is considered to contribute to the beneficial effects of stroke units, but there are uncertainties regarding the optimal time to start mobilization. We hypothesized that VEM within 24 hours after admittance to the hospital would reduce poor outcome 3 months poststroke compared with mobilization between 24 and 48 hours.

Methods—

We conducted a prospective, randomized, controlled trial with blinded assessment at follow-up. Patients admitted to the stroke unit within 24 hours after stroke were assigned to either VEM within 24 hours of admittance or mobilization between 24 and 48 hours (control group). Primary outcome was the proportion of poor outcome (modified Rankin scale score, 3–6), whereas secondary outcomes were death rate, change in neurological impairment (National Institutes of Health Stroke Scale score), and dependency (Barthel Index 0–17).

Results—

Fifty-six patients were included (mean age±SD, 76.9±9.4 years), 27 were in the VEM group and 29 were in the control group. VEM patients had nonsignificant higher odds (adjusted for age and National Institutes of Health Stroke Scale score on admission) of poor outcome (OR, 2.70; 95% CI, 0.78–9.34;
P
=0.12), death (OR, 5.26; 95% CI, 0.84–32.88;
P
=0.08), and dependency (OR, 1.25; 95% CI, 0.36–4.34;
P
=0.73). The control group, having milder strokes (National Institutes of Health Stroke Scale score±SD: control group, 7.5±4.2; VEM, 9.2±6.5;
P
=0.26), had better neurological improvement (
P
=0.02).

Conclusions—

We identified a trend toward increased poor outcome, death rate, and dependency among patients mobilized within 24 hours after hospitalization, and an improvement in neurological functioning in favor of patients mobilized between 24 and 48 hours. Very early or delayed mobilization after acute stroke is still undergoing debate, and results from ongoing larger trials are required.
Reperfusion Rather than Ischemia Drives the Formation of Ubiquitin Aggregates After Middle Cerebral Artery Occlusion
Authors: Hochrainer Karin , Jackman Katherine , Anrather Josef , Iadecola Costantino
Published: June 2012

Background and Purpose—

Cerebral ischemia leads to accumulation of ubiquitinated protein aggregates. However, the factors triggering ubiquitination and their impact on the outcome of cerebral ischemia remain poorly understood. Here we investigate the relationship between ubiquitin aggregation and duration of ischemia/reperfusion, infarct volume, and proteasomal activity in a mouse model of focal ischemia.

Methods—

Free ubiquitin and ubiquitin aggregate levels were examined by Western blotting in the mouse neocortex and striatum after different periods of ischemia/reperfusion and permanent ischemia induced by middle cerebral artery occlusion. Infarct volumes were measured in thionin-stained brain sections. Proteasome activity was studied by fluorometric peptidase activity assay.

Results—

Following transient ischemia, ubiquitin aggregates were detected in the ipsilateral neocortex and, to a lesser extent, striatum only after induction of reperfusion. In permanent ischemia, no ubiquitin aggregates were found. Shorter ischemic periods producing no or minimal tissue damage (10–15 minutes) resulted in ubiquitin aggregate levels similar to those produced by ischemia resulting in substantial infarction (30 minutes). Proteasomal impairment was greatest in ischemia without reperfusion, in which no ubiquitin aggregates were detected.

Conclusions—

The data demonstrate that reperfusion rather than ischemia leads to the appearance of ubiquitinated aggregates, which form in the absence of major tissue damage and are not correlated with decreased proteasomal peptidase activity. Ubiquitin aggregates may form in potentially viable brain tissue, which may be later recruited into infarction by factors independent of ubiquitination.
Declining Stroke and Myocardial Infarction Mortality Between 1989 and 2010 in a Country of the African Region
Authors: Stringhini Silvia , Sinon Flavie , Didon Joaquim , Gedeon Jude , Paccaud Fred , Bovet Pascal
Published: June 2012

Background and Purpose—

In low- and middle-income countries, the total burden of cardiovascular diseases is expected to increase due to demographic and epidemiological transitions. However, data on cause-specific mortality are lacking in sub-Saharan Africa. Seychelles is one of the few countries in the region where all deaths are registered and medically certified. In this study, we examine trends in mortality for stroke and myocardial infarction (MI) between 1989 and 2010.

Methods—

Based on vital statistics, we ascertained stroke and MI as the cause of death if appearing in any of the 4 fields for immediate, intermediate, underlying, and contributory causes in death certificates.

Results—

Mortality rates (per 100 000, age-standardized to World Health Organization standard population) decreased from 1669/710 (men/women) in 1989 to 1991 to 1113/535 in 2008–10 for all causes, from 250/140 to 141/86 for stroke, and from 117/51 to 59/24 for MI, corresponding to proportionate decreases of 33%/25% for all-cause mortality, 44%/39% for stroke, and 50%/53% for MI over 22 years. The absolute number of stroke and MI deaths did not increase over time. In 2008 to 2010, the median age of death was 65/78 years (men/women) for all causes, 68/78 for stroke, and 66/73 for MI.

Conclusions—

Between 1989 and 2010, age-standardized stroke and MI mortality decreased markedly and more rapidly than all-cause mortality. The absolute number of cardiovascular disease deaths did not increase over time because the impact of population aging was fully compensated by the decline in cardiovascular disease mortality. Stroke mortality remained high, emphasizing the need to strengthen cardiovascular disease prevention and control.