bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Coordinated Formation for Multiple Surface Vessels Based on Backstepping Sliding Mode Control
Authors: Fu Mingyu , Jiao Jianfang , Yin Shen
Published: September 2013

We investigate the problem of coordinated formation control for multiple surface vessels in the presence of unknown external disturbances. In order to realize the leaderless coordinated formation and achieve the robustness against unknown external disturbances, a new robust coordinated formation control algorithm based on backstepping sliding mode control is proposed. The proposed coordinated control algorithm is achieved by defining a new switched function using the combination of position tracking error and cross-coupling error. Particularly, the cross-coupling error is defined using velocity tracking error and velocity synchronization error so as to be applicable for sliding mode controller design. Furthermore, the adaptive control law is proposed to estimate unknown disturbances for each vessel. The globally asymptotically stability is proved using the Lyapunov direct method. Finally, the effectiveness of the proposed coordinated formation control algorithm is demonstrated by corresponding simulations.
Physiological Parameters of Endurance Horses Pre- Compared to Post-Race, Correlated with Performance: A Two Race Study from Scandinavia
Authors: Larsson J. , Pilborg P. H. , Johansen M. , Christophersen M. T. , Holte A. , Roepstorff L. , Olsen L. H. , Harrison A. P.
Published: September 2013

Few studies have investigated the physiological parameters of endurance horses in Scandinavia. Hence, this two race study has focused on the effects of endurance racing in terms of equine clinicopathological blood parameters, heart score, and fluid use. Race A involved 15 horses (120 km). Two pre- and one post-race blood samples were taken, body condition score was assessed in triplicate pre-race, and an ECG was used to determine heart score. Race B involved 16 horses (65–120 km). One pre- and two post-race blood samples were taken. For both races, horse data as well as fluid intake estimates and cooling water were noted. Race A showed that blood haematocrit, albumin, sodium, and triglycerides increased significantly with endurance racing, whilst chloride, glucose, iron, and potassium decreased significantly. In race B, blood creatinine, cholesterol, and inorganic phosphate continued to increase significantly during the first post-race sampling period compared to pre-race levels, whilst iron, which decreased significantly during the race, increased significantly over the two post-race sampling periods. It is concluded that whilst no correlation between heart score and speed was observed, a significant correlation exists between experience and changes in blood parameters with endurance racing and between fluid intake and average speed.
Uncertainty Estimation due to Geometrical Imperfection and Wringing in Calibration of End Standards
Authors: Ali Salah H. R. , Naeim Ihab H.
Published: September 2013

Uncertainty in gauge block measurement depends on three major areas, thermal effects, dimension metrology system that includes measurement strategy, and end standard surface perfection grades. In this paper, we focus precisely on estimating the uncertainty due to the geometrical imperfection of measuring surfaces and wringing gab in calibration of end standards grade 0. Optomechanical system equipped with Zygo measurement interferometer (ZMI-1000A) and AFM technique have been employed. A novel protocol of measurement covering the geometric form of end standard surfaces and wrung base platen was experimentally applied. Surface imperfection characteristics of commonly used 6.5 mm GB have been achieved by AFM in 2D and 3D to be applied in three sets of experiments. The results show that there are obvious mapping relations between the geometrical imperfection and wringing thickness of the end standards calibration. Moreover, the predicted uncertainties are clearly estimated within an acceptable range from 0.132 µm, 0.164 µm and 0.202 µm, respectively. Experimental and analytical results are also presented.
A Rare Entity of Benign Recurring Mesenchymal Tumor of the Female Urethra
Authors: Telli Onur , Sarıcı Haşmet , Özgür Berat Cem , Yücetürk Cem Nedim , Karagöz Mehmet Ali
Published: September 2013

This is a case report of a 51-year-old female patient with benign mesenchymal tumors of paraurethral region which caused lower urinary tract symptoms. The pathological examination of the lesion was reported as angiomyxoma which is a distinct soft tissue tumor characterized by the presence of prominent myxoid matrix and numerous thin-walled blood vessels. This tumor has a predilection for the trunk, head and neck, extremities, and genitalia. It is a benign tumor, and total excision is curative. Recurrence is rare except for aggressive angiomyxomas.
The DTN Routing Algorithm Based on Markov Meeting Time Span Prediction Model
Authors: Wang En , Yang Yongjian , Jia Bing , Guo Tingting
Published: September 2013

Putting forward an efficient routing algorithm in DTN (delay tolerant network) has become a focus of attention due to the existing phenomena that the connections between nodes in the network change dramatically over time and the communications suffer from frequent disruptions. In this paper, the meeting time span between nodes is predicted using the Markov model, and the relay node holding the shortest meeting time span with the destination node is determined as the most efficient node. In the two phases, spray phase and wait phase, the message is routed according to the utility value. Thus, the routing algorithm based on Markov meeting time span prediction model is provided. Simulation results suggest that this algorithm efficiently improves the delivery rate and reduces the average delay.
Recurrent Ectopic Pregnancy in the Tubal Remnant after Salpingectomy
Authors: Samiei-Sarir Bahareh , Diehm Christopher
Published: September 2013

We present two cases of ectopic pregnancy located within the remnant tube following ipsilateral salpingectomy. This particular pathology is rare and yet has significant consequences for the patient, with mortality rates 10–15 times higher than other ectopic pregnancies. It demonstrates that salpingectomy does not exclude ectopic pregnancy on the ipsilateral side. We suggest careful clinical consideration and bring attention to the current surgical technique.
Total Hip Arthroplasty with Bulk Femoral Head Autograft for Acetabular Reconstruction in Developmental Dysplasia of the Hip
Authors: Pizarro Fernando Claros , Young Simon W. , Blacutt Jorge H. , Mojica Rolando , Cruz Juan C.
Published: September 2013

Developmental hip dysplasia (DDH) presents considerable technical challenges to the primary arthroplasty surgeon. Autogenous bulk grafting using the femoral head has been utilised to achieve anatomic cup placement and superolateral bone coverage in these patients, but reported outcomes on this technique have been mixed with the lack of graft integration and subsequent collapse, an early cause of failures. We describe a novel technique combining the use of bulk autograft with an iliac osteotomy, which provides primary stability and direct cancellous-cancellous bone contact, optimising the environment for early osseointegration. Twenty-one hips in 21 patients with DDH underwent this technique and were followed for a mean of 8.1 years. The preoperative radiographic classification was Crowe type I in 12 hips (57%), type II in 4 hips, and type III in 5 hips, and the mean Sharp angle was 49.6° (range 42°–60°). All grafts united by year. At time of followup, there was no radiographic evidence of graft collapse or loosening. There were no reoperations. Our study has shown that this technique variation combining an iliac osteotomy with bulk autograft in cases of developmental hip dysplasia provides early stability and reliable graft incorporation, together with satisfactory clinical and radiological outcomes in the medium term. Longer term study is necessary to confirm the clinical success of this procedure.
The Effect of Weight Loss in Obese Patients with Chronic Stable Plaque-Type Psoriasis
Authors: Roongpisuthipong Wanjarus , Pongpudpunth Marinya , Roongpisuthipong Chulaporn , Rajatanavin Natta
Published: September 2013

Background. Chronic plaque psoriasis is frequently associated with obesity. The effect of a low-calorie diet on psoriasis has not been investigated.Objective. The objective was to investigate whether moderate weight loss increases the therapeutic response to topical treatment in obese patients with chronic stable plaque-type psoriasis.Material and Method. A 24-week clinical trial was conducted in 10 patients. The efficacy of a low-calorie diet with topical treatment was compared with baseline in obese patients with chronic stable plaque-type psoriasis. The primary measure of clinical response was the Psoriasis Area and Severity Index at weeks 12 and 24.Results. At week 12, the mean reduction in body weight was 9.6 percent. There was an improvement from baseline of 50 percent or more in the Psoriasis Area and Severity Index in 50 percent of the patients. The responses as measured by improvements in the Psoriasis Area and Severity Index were paralleled by improvements in global assessments by the physician and the patients and in the Dermatology Life Quality Index.Conclusion. Obese patients with chronic stable plaque-type psoriasis increase their response to a low-calorie diet. Lifestyle modifications, including a low-calorie diet, may supplement the pharmacologic treatment of obese psoriasis patients.
Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13)(q26.2;p11.2): Further Delineation of 3q Duplication Syndrome
Authors: Abreu-González M. , García-Delgado C. , Cervantes A. , Aparicio-Onofre A. , Guevara-Yáñez R. , Sánchez-Urbina R. , Gallegos-Arreola M. P. , Luna-Angulo A. , Estrada F. J. , Morán-Barroso V. F.
Published: September 2013

Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.
Existence and Uniqueness of a Solution in the Space of BV Functions to the Equation of a Vibrating Membrane with a “Viscosity” Term
Authors: Kikuchi Koji
Published: September 2013

A nonlinear equation of motion of vibrating membrane with a “viscosity” term is investigated. Usually, the term is added, and it is well known that this equation is well posed in the space of functions. In this paper, the viscosity term is changed to , and it is proved that if initial data is slightly smooth (but belonging to is sufficient), then a weak solution exists uniquely in the space of BV functions.
Nearest-Neighbor Interactions and Their Influence on the Structural Aspects of Dipeptides
Authors: Das Gunajyoti , Mandal Shilpi
Published: September 2013

In this theoretical study, the role of the side chain moiety of C-terminal residue in influencing the structural and molecular properties of dipeptides is analyzed by considering a series of seven dipeptides. The C-terminal positions of the dipeptides are varied with seven different amino acid residues, namely. Val, Leu, Asp, Ser, Gln, His, and Pyl while their N-terminal positions are kept constant with Sec residues. Full geometry optimization and vibrational frequency calculations are carried out at B3LYP/6-311++G(d,p) level in gas and aqueous phase. The stereo-electronic effects of the side chain moieties of C-terminal residues are found to influence the values ofΦandΩdihedrals, planarity of the peptide planes, and geometry around the C7  α-carbon atoms of the dipeptides. The gas phase intramolecular H-bond combinations of the dipeptides are similar to those in aqueous phase. The theoretical vibrational spectra of the dipeptides reflect the nature of intramolecular H-bonds existing in the dipeptide structures. Solvation effects of aqueous environment are evident on the geometrical parameters related to the amide planes, dipole moments, HOMOLUMO energy gaps as well as thermodynamic stability of the dipeptides.
Opioid Therapy Pharmacogenomics for Noncancer Pain: Efficacy, Adverse Events, and Costs
Authors: Xu Yan , Johnson Ana
Published: September 2013

Chronic non-cancer pain is a debilitating condition associated with high individual and societal costs. While opioid treatment for pain has been available for centuries, it is associated with high variability in outcome, and a considerable proportion of patients is unable to attain relief from symptoms while suffering adverse events and developing medication dependence. We performed a review of the efficacy of pharmacogenomic markers and their abilities to predict adverse events, dependence, and associated economic costs, focusing on two genes: OPRM1 and CYP2D6. Data sources were articles indexed by PubMed on or before August 6, 2013. Articles were first selected after review of their titles and abstracts, and full papers were read to confirm eligibility. Initially, fifty-two articles were identified. Of these, 17 were relevant to biological actions of pharmacogenomic markers and their effect on therapeutic efficacy, 16 to adverse events, 15 to opioid dependence, and eight to economic costs. In conclusion, increasing costs of opioid therapy have made the advances in pharmacogenomics an attractive solution to personalize care with unclear repercussions related to the impact on costs, morbidity, and outcomes. This intersection of pharmacoeconomics and pharmacogenomics presents a unique platform to further examine current advances in clinical medicine and their utility in cost-effective treatment of chronic pain.
Acute Hemolysis in the Emergency Department: Think aboutClostridium perfringens!
Authors: Cécilia Roustit , Baptiste Vallé , Benjamin Clouzeau , Virginie Heydel , Guillaume Valdenaire , Philippe Revel , Matthieu Biais
Published: September 2013

Clostridium perfringens(CP) gives several clinical settings, from an asymptomatic to a massive intravascular hemolysis. We report a case of fatal intravascular hemolysis due to CP septicemia having a hepatic supposed starting point in the emergency department. Like in many cases, the diagnosis was made when patient had already gone into shock and died. The CP septicemia often complicated the course of the digestive or genital pathologies. The alpha toxin can damage the structural integrity of the red cell membrane by means of a phospholipase activity. Nevertheless, a massive intravascular hemolysis arises only rarely in this septicemia, only from 7 to 15% of the cases. The emergency physician has to think about this complication in case of hemoglobinuria and/or signs of hemolysis associated with a septic syndrome. An immediate antibiotic treatment adapted as well as the symptomatic treatment of the spread intravascular coagulation could improve the survival of these patients.
Antioxidant and Antiproliferative Activities of Leaf Extracts fromPlukenetia volubilisLinneo (Euphorbiaceae)
Authors: Nascimento Ana Karina Lima , Melo-Silveira Raniere Fagundes , Dantas-Santos Nednaldo , Fernandes Júlia Morais , Zucolotto Silvana Maria , Rocha Hugo Alexandre Oliveira , Scortecci Katia Castanho
Published: September 2013

Plukenetia volubilisLinneo, or Sacha inca, is an oleaginous plant from the Euphorbiaceae family. The aim of this work was to perform a chemical and biological analysis of different leaf extracts fromP. volubilissuch as aqueous extract (AEL), methanol (MEL), ethanol (EEL), chloroform (CEL), and hexane (HEL). Thin layer chromatography analysis revealed the presence of phenolic compounds, steroids, and/or terpenoídes. Furthermore, the antioxidant activities were analyzed byin vitroassays and their effects on cell lineages byin vivoassays. The Total Antioxidant Capacity (TCA) was expressed as equivalent ascorbic acid (EEA/g) and it was observed that the extracts showed values ranging from 59.31 to 97.76 EAA/g. Furthermore, the DPPH assay values ranged from 62.8% to 88.3%. The cell viability assay showed that the extracts were able to reduce viability from cancer cells such as HeLa and A549 cells. The extracts MEL and HEL (250 µg/mL) were able to reduce the proliferation of HeLa cells up to 54.3% and 48.5%, respectively. The flow cytometer results showed that these extracts induce cell death via the apoptosis pathway. On the other hand, the extracts HEL and AEL were able to induce cell proliferation of normal fibroblast 3T3 cells.
Magnetic Properties and Microstructure of FeOx/Fe/FePt and FeOx/FePt Films
Authors: Tsai Jai-Lin , Chen Po-Ran , Chen Yi-Hsiu , Luo Qi-Shao
Published: September 2013

The Fe(6 nm)/FePt film with perpendicular magnetization was deposited on the glass substrate. To study the oxygen diffusion effect on the coupling of Fe/FePt bilayer, the plasma oxidation with 0.5~7% oxygen flow ratio was performed during sputtered part of Fe layer and formed the FeOx(3 nm)/Fe(3 nm)/FePt trilayer. Two‐step magnetic hysteresis loops were found in trilayer with oxygen flow ratio above 1%. The magnetization in FeOx and Fe/FePt layers was decoupled. The moments in FeOx layer were first reversed and followed by coupled Fe/FePt bilayer. The trilayer was annealed again at 500°C and 800°C for 3 minutes. When the FeOx(3 nm)/Fe(3 nm)/FePt trilayer was annealed at 500°C, the layers structure was changed to FeOx(6 nm)/FePt bilayer due to oxygen diffusion. The hard‐magnetic FeOx(6 nm)/FePt film was coupled with single switching field. The FeOx/(disordered FePt) layer structure was observed with further annealing at 800°C and presented soft‐magnetic loop. In summary, the coupling between soft‐magnetic Fe, FeOx layer, and hard‐magnetic L10 FePt layer can be controlled by the oxygen diffusion behavior, and the oxidation of Fe layer was tuned by the annealing temperature. The ordered L10 FePt layer was deteriorated by oxygen and became disordered FePt when the annealed temperature was up to 800°C.
Vascular Supply to the Liver: A Report of a Rare Arterial Variant
Authors: Johnson Peter B. , Cawich Shamir O. , Shah Sundeep , Gardner Michael T. , Roberts Patrick , Stedman Brian , Pearce Neil W.
Published: September 2013

In the classic description of hepatic arterial supply, the common hepatic artery originates from the coeliac trunk. However, there are numerous variations to this classic pattern. We report a rare variant pattern of hepatic arterial supply and discuss the clinical significance of this variation.
Effects of the Argon Pressure on the Optical Band Gap of Zinc Oxide Thin Films Grown by Nonreactive RF Sputtering
Authors: Acosta M. , Riech I. , Martín-Tovar E.
Published: September 2013

Zinc oxide (ZnO) thin films were grown by nonreactive RF sputtering at room temperature under varying argon pressures (PAr). Their optical band gap was found to increase from 3.58 to 4.34 eV when the argon pressure increases from 2.67 to 10.66 Pa. After annealing at 200°C and 500°C, optical band gaps decrease considerably. The observed widening of the band gap with increasingPArcan be understood as being a consequence of the poorer crystallinity of films grown at higher pressures. Measurements of morphological and electrical properties of these films correlate well with this picture. Our main aim is to understand the effects ofPAron several physical properties of the films, and most importantly on its optical band gap.
P90RSK and Nrf2 Activation via MEK1/2-ERK1/2 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells
Authors: Meng Xiang-Bao , Sun Gui-Bo , Wang Min , Sun Jing , Qin Meng , Sun Xiao-Bo
Published: September 2013

6-Hydroxydopamine (6-OHDA) is known to contribute to neuronal death in Parkinson's disease. In this study, we found that the preincubation of SH-SY5Y cells for 24 h with 20 μM notoginsenoside R2 (NGR2), which is a newly isolated notoginsenoside fromPanax notoginseng, showed neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis. NGR2 incubation successively resulted in the activation of P90RSK, inactivation of BAD, and inhibition of 6-OHDA-induced mitochondrial membrane depolarization, thus preventing the mitochondrial apoptosis pathway. NGR2 incubation also led to the activation of Nrf2 and subsequent activity enhancement of phase II detoxifying enzymes, thus suppressing 6-OHDA-induced oxidative stress, and these effects could be removed by Nrf2 siRNA. We also found that the upstream activators of P90RSK and Nrf2 were the MEK1/2–ERK1/2 pathways but not the JNK, P38, or PI3K/Akt pathways. Interestingly, NGR2 incubation could also activate MEK1/2 and ERK1/2. Most importantly, NGR2-mediated P90RSK and Nrf2 activation, respective downstream target activation, and neuroprotection were reversed by the genetic silencing of MEK1/2 and ERK1/2 by using siRNA and PD98059 application. These results suggested that the neuroprotection elicited by NGR2 against 6-OHDA-induced neurotoxicity was associated with NGR2-mediated P90RSK and Nrf2 activation through MEK1/2-ERK1/2 pathways.
Bispecific Antibody to ErbB2 Overcomes Trastuzumab Resistance through Comprehensive Blockade of ErbB2 Heterodimerization
Authors: Li Bohua , Meng Yanchun , Zheng Lei , Zhang Xunmin , Tong Qing , Tan Wenlong , Hu Shi , Li Hui , Chen Yang , Song Jinjing , Zhang Ge , Zhao Lei , Zhang Dapeng , Hou Sheng , Qian Weizhu , Guo Yajun
Published: September 2013

The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. However, resistance to trastuzumab is common. Heterodimerization between ErbB2 and other ErbBs may redundantly trigger cell proliferation signals and confer trastuzumab resistance. Here, we developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, another ErbB2-specific humanized antibody that binds to a distinct epitope from trastuzumab. This bispecific antibody, denoted as TPL, retained the full binding activities of both parental antibodies and exhibited pharmacokinetic properties similar to those of a conventional immunoglobulin G molecule. Unexpectedly, TPL showed superior ErbB2 heterodimerization-blocking activity over the combination of both parental monoclonal antibodies, possibly through steric hindrance and/or inducing ErbB2 conformational change. Further data indicated that TPL potently abrogated ErbB2 signaling in trastuzumab-resistant breast cancer cell lines. In addition, we showed that TPL was far more effective than trastuzumab plus pertuzumab in inhibiting the growth of trastuzumab-resistant breast cancer cell lines, both in vitro and in vivo. Importantly, TPL treatment eradicated established trastuzumab-resistant tumors in tumor-bearing nude mice. Our results suggest that trastuzumab-resistant breast tumors remain dependent on ErbB2 signaling and that comprehensive blockade of ErbB2 heterodimerization may be an effective therapeutic avenue. The unique potential of TPL to overcome trastuzumab resistance warrants its consideration as a promising treatment in the clinic. Cancer Res; 73(21); 6471–83. ©2013 AACR.
Impact of Cardiovascular Comorbidity on Ovarian Cancer Mortality
Authors: Shinn Eileen H. , Lenihan Daniel J. , Urbauer Diana L. , Basen-Engquist Karen M. , Valentine Alan , Palmero Laura , Woods Myrshia L. , Patel Pooja , Nick Alpa M. , Shahzad Mian M.K. , Stone Rebecca L. , Golden Antoinette , Atkinson Emma , Lutgendorf Susan K. , Sood Anil K.
Published: September 2013

Background: A retrospective cohort study utilizing prospectively collected data was conducted from August 2003 until March 2008 at M.D. Anderson Cancer Center. It is unknown whether cardiovascular comorbidity and chronic stress impact ovarian cancer outcome, which remains poor despite advances in therapy. The purpose of this study was to determine whether cardiovascular disease and markers that may be associated with stress are also associated with survival in patients with ovarian cancer.

Methods: Participants with newly diagnosed epithelial ovarian cancer were followed until time of death or truncation of study period (median follow-up = 4.2 years; n = 271). Tumor characteristics (stage, tumor grade, histology, debulking status), demographic variables, and cardiovascular comorbidity were documented and compared to overall survival.

Results: Of the nine cardiovascular events tracked during follow-up, venous thromboembolism [VTE; HR, 3.2; 95% confidence interval (CI), 1.8–5.5] and pulmonary hypertension (HR, 8.5; 95% CI, 3.9–18.7) were associated with shorter survival in multivariate analysis. In addition, high tumor grade, suboptimal cytoreduction, and baseline heart rate (HR, 1.02; 95% CI, 1.01–1.04) were related to decreased survival.

Conclusion: Careful management of certain cardiovascular comorbidities may extend survival in patients with ovarian cancer. Our findings suggest that increased baseline heart rate and the development of VTE and pulmonary hypertension after cancer diagnosis may be significant predictors of survival in women with ovarian cancer.

Impact: Our study emphasizes the importance of identifying and optimally treating tachycardia, VTE, and pulmonary hypertension in conjunction with cancer therapy. Cancer Epidemiol Biomarkers Prev; 22(11); 2102–9. ©2013 AACR.
Genetic Variation in the Inflammation and Innate Immunity Pathways and Colorectal Cancer Risk
Authors: Wang Hansong , Taverna Darin , Stram Daniel O. , Fortini Barbara K. , Cheng Iona , Wilkens Lynne R. , Burnett Terrilea , Makar Karen W. , Lindor Noralane M. , Hopper John L. , Gallinger Steve , Baron John A. , Haile Robert , Kolonel Laurence N. , Henderson Brian E. , Newcomb Polly A. , Casey Graham , Duggan David , Ulrich Cornelia M. , Le Marchand Loïc
Published: September 2013

Background: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.

Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls).

Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the “effective” number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822.

Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk.

Impact: Further replication in independent samples is warranted. Cancer Epidemiol Biomarkers Prev; 22(11); 2094–101. ©2013 AACR.
Hypoxic Activation of the PERK/eIF2α Arm of the Unfolded Protein Response Promotes Metastasis through Induction of LAMP3
Authors: Mujcic Hilda , Nagelkerke Anika , Rouschop Kasper M.A. , Chung Stephen , Chaudary Naz , Span Paul N. , Clarke Blaise , Milosevic Michael , Sykes Jenna , Hill Richard P. , Koritzinsky Marianne , Wouters Bradly G.
Published: September 2013

Purpose: Conditions of poor oxygenation (hypoxia) are present in many human tumors, including cervix cancer, and are associated with increased risk of metastasis and poor prognosis. Hypoxia is a potent activator of the PERK/eIF2α signaling pathway, a component of the unfolded protein response (UPR) and an important mediator of hypoxia tolerance and tumor growth. Here, the importance of this pathway in the metastasis of human cervix carcinoma was investigated.

Experimental Design: Amplification and expression of LAMP3, a UPR metastasis-associated gene, was examined using FISH and immunofluorescence in a cohort of human cervix tumors from patients who had received oxygen needle electrode tumor oxygenation measurements. To evaluate the importance of this pathway in metastasis in vivo, we constructed a series of inducible cell lines to interfere with PERK signaling during hypoxia and used these in an orthotopic cervix cancer model of hypoxia-driven metastasis.

Results: We show that LAMP3 expression in human cervix tumors is augmented both by gene copy number alterations and by hypoxia. Induced disruption of PERK signaling in established orthotopic xenografts resulted in complete inhibition of hypoxia-induced metastasis to the lymph nodes. This is due, in part, to a direct influence of the UPR pathway on hypoxia tolerance. However, we also find that LAMP3 is a key mediator of hypoxia-driven nodal metastasis, through its ability to promote metastatic properties including cell migration.

Conclusion: These data suggest that the association between hypoxia, metastasis, and poor prognosis is due, in part, to hypoxic activation of the UPR and expression of LAMP3. Clin Cancer Res; 19(22); 6126–37. ©2013 AACR.
miR-106a Represses the Rb Tumor Suppressor p130 to Regulate Cellular Proliferation and Differentiation in High-Grade Serous Ovarian Carcinoma
Authors: Liu Zhaojian , Gersbach Elizabeth , Zhang Xiyu , Xu Xiaofei , Dong Ruifen , Lee Peng , Liu Jinsong , Kong Beihua , Shao Changshun , Wei Jian-Jun
Published: September 2013

The degree of differentiation in human cancers generally reflects the degree of malignancy, with the most undifferentiated cancer being also the highest grade and the most aggressive. High-grade serous ovarian carcinomas (HGSOC) are poorly differentiated and fast-growing malignancies. The molecular mechanisms underlying the poor differentiation of HGSOC has not been completely characterized. Evidence suggests that miRNA, miR are dysregulated in HGSOC. Therefore, we focused on those miRNAs that are relevant to tumor differentiation. Expression profiling of miRNAs in HGSOC, indicated miR-106a and its family members were significantly upregulated. Upregulation of miR-106a was further validated by real-time reverse transcriptase PCR (qRT-PCR) and miRNA in situ hybridization in a large cohort of HGSOC specimens. Overexpression of miR-106a in benign and malignant ovarian cells significantly increased the cellular proliferation rate and expanded the side-population fraction. In particular, SKOV3 cells with miR-106a overexpression had significantly higher tumor initial/stem cell population (CD24- and CD133-positive cells) than control SKOV3 cells. Among many miR-106a predicated target genes, p130 (RBL2), an retinoblastoma (Rb) tumor suppressor family member, was not only confirmed as a specific target of miR-106a but also related to tumor growth and differentiation. The importance of mir-106a and RBL2 was further demonstrated in vivo, in which, SKOV3 cells overexpressing miR-106a formed poorly differentiated carcinomas and had reduced RBL2 levels. To our knowledge, this is the first study of miR-106a mediating proliferation and tumor differentiation in HGSOC.

Implications: The current study suggests that the RB tumor suppressor pathway is a critical regulator of growth and differentiation in HGSOC. Mol Cancer Res; 11(11); 1314–25. ©2013 AACR.
Introduction of an Enhanced Recovery Protocol to Reduce Short-Term Complications following Radical Cystectomy and Intestinal Urinary Diversion with Vescica Ileale Padovana Neobladder
Authors: Cerruto Maria Angela , De Marco Vincenzo , D'Elia Carolina , Bizzotto Leonardo , Curti Pierpaolo , Baldassarre Roberto , Artibani Walter
Published: September 2013

Objectives: To reduce short-term complications of radical cystectomy (RC) and intestinal urinary diversion with vescica ileale Padovana (VIP) neobladder, we described and assessed an enhanced recovery protocol (ERP) in a series of consecutive patients. Methods: An ERP was introduced focusing on reduced bowel preparation, standardized feeding and analgesic regimens. We analyzed the outcomes with all patients consecutively undergoing RC and VIP neobladder who met the following inclusion criteria: American Society of Anesthesiologists score <3; absence of malnutrition according to the Mini Nutritional Assessment - Short Form criteria; absence of inflammatory bowel diseases. Results: Thirty-one consecutive patients were recruited to undergo our ERP. Mean age of patients was 62.16 years. No patients died due to surgical complications. Nine of 31 patients experienced complications (29.03%), none requiring surgical intervention. According to Clavien grading, all complications were grade <2. Conclusion: The application of our ERP to our patients undergoing RC and VIP neobladder contributed to reduce postoperative morbidity.
Serum Adiponectin, Anemia and Left Ventricular Dimensions in Patients with Cardiac Cachexia
Authors: Bozcali Evin , Polat Veli , Akbulut Handan , Ferzeyn Yavuzkir Mustafa , Karaca Ilgin
Published: September 2013

Objectives: Our study aims to determine the role of serum adiponectin in chronic heart failure (CHF) and cardiac cachexia (CC). Methods: Ninety consecutive patients were included in the study. Patients were divided into three groups: 30 CHF patients with CC, 30 CHF patients without CC, and 30 healthy individuals. Adiponectin levels were measured through human ELISA kits. Results: Levels of serum adiponectin were significantly higher in the CHF patients with cachexia in comparison with the other groups (CHF with CC: 58.4 ± 15.5 ng/ml vs. CHF without CC: 24 ± 6.7 ng/ml and controls: 7.7 ± 3.4 ng/ml; p = 0.001). Serum adiponectin was negatively correlated with BMI, high-sensitivity C-reactive protein, and hemoglobin (r = -0.37, p = 0.02; r = -0.29, p = 0.02; r = -0.18, p = 0.03, respectively) in the CHF patients with cachexia. Additionally, serum adiponectin levels were positively correlated with B-type natriuretic protein levels, left ventricle end-diastolic and end-systolic diameters (r = 0.36, p = 0.02; r = 0.46, p = 0.01; r = 0.49, p = 0.006, respectively) in the CHF patients with cachexia. Conclusion: Our findings suggest that adiponectin may play a critical role in the pathogenesis of cardiac remodeling and anemia in CC.
Pharmacokinetics of Daily Daptomycin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy
Authors: Corti Natascia , Rudiger Alain , Chiesa Alessandro , Marti Isabelle , Jetter Alexander , Rentsch Katharina , Müller Daniel , Béchir Markus , Maggiorini Marco
Published: September 2013

Background: The optimal daptomycin dosing regimen for critically ill patients undergoing continuous renal replacement therapy (CRRT) has still to be established. Methods: Daptomycin pharmacokinetics was determined in 9 patients after administration of 6 mg/kg/day over 5 days. Results: At steady state, which was reached by day 3, the area under the curve over 24 h (AUC24h) was 667.4 ± 356.6 mg·h/l, and the maximum concentration (Cmax) was 66.9 ±25.3 mg/l. Mean CRRT clearance accounted for 48% (range 32-67%) of total clearance (mean 10.2 ml/min, range 6.1-18 ml/min). Significant correlations were observed between Cmax, minimum concentration (Cmin) and AUC24h (R2 = 0.91, p < 0.001, and R2 = 0.94, p < 0.001) and between albumin plasma concentration and free daptomycin (R2 = 0.7, p = 0.009). Conclusion: No significant accumulation occurred with a daily daptomycin dose of 6 mg/kg in patients undergoing CRRT with an effluent flow rate of >30 ml/kg/h. The quantification of trough concentrations (Cmin) appears to be a good surrogate to estimate AUC24h and to monitor daptomycin treatment in patients undergoing CRRT.
Spinal Cord Injury without Radiographic Abnormality and the Chiari Malformation: Controlled Observations
Authors: Piatt Jr. Joseph H. , Campbell Jeffrey W.
Published: September 2013

Background: Case reports have suggested an association between the Chiari malformation type 1 (CM1) and spinal cord injury without radiographic abnormality (SCIWORA). No controlled observations have appeared. We report a case-control study. Methods: The Kids' Inpatient Database (KID) is a product of the Healthcare Utilization Project of the Agency for Healthcare Research and Quality. For the years 1997, 2000, 2003, 2006, and 2009, the KID includes discharge data abstracted from almost 14 million pediatric admissions. We hypothesized that CM1 predisposes children to SCIWORA in the cervicomedullary region, and we reasoned that, if this hypothesis were true, then KID admissions coded for upper cervical SCIWORA would be associated with CM1 more frequently than admissions coded for lower cervical SCIWORA. Results: After exclusion of admissions with a variety of confounding diagnostic codes, we identified 754 admissions coded for upper cervical SCIWORA and 424 coded for lower cervical SCIWORA. Concurrent coding for CM1 was more prevalent among admissions coded for upper cervical SCIWORA than for lower cervical SCIWORA, but the difference did not attain statistical significance (p = 0.093; Fisher's exact test). Conclusions: These controlled observations fail to support the hypothesis that CM1 is associated with SCIWORA in childhood. If there is a real association, in the context of recent estimates of the prevalence of CM1 in the pediatric population, the magnitude of the incremental risk must be very small.
Tat Pathway-Mediated Translocation of the Sec Pathway Substrate OprM, an Outer Membrane Subunit of the Resistance Nodulation Division Xenobiotic Extrusion Pumps, in Pseudomonas Aeruginosa
Authors: Akiba K. , Ando T. , Isogai E. , Nakae T. , Yoneyama H.
Published: September 2013

Background: Pseudomonas aeruginosa produces the Sec and Tat protein secretion machineries. The latter appears to be involved in the secretion of virulence factors, including phospholipase C (PlcH), and hence is a potential target of chemotherapeutic agents. Methods: The signal sequence of OprM, the outer membrane subunit of the xenobiotic extrusion pumps, was substituted with that of PlcH. The antibiotic susceptibility of oprM-deficient cells expressing the hybrid protein PlcH-OprM was evaluated using the agar dilution method. Results: The PlcH-OprM-expressing cells showed resistance to various MexAB-OprM substrate antibiotics. To evaluate the translocation route of PlcH-OprM, tatC encoding an indispensable component of the Tat machinery was knocked out in oprM-deficient cells. The tatC-oprM double mutant expressing PlcH-OprM exhibited antibiotic hypersusceptibility like the oprM-deficient cells, indicating that PlcH-OprM was translocated across the inner membrane exclusively through the Tat system. Conclusions: This system can be used for the screening of Tat system inhibitors and will be an excellent model for the study of secretion and biogenesis of the β-barrel outer membrane proteins.
Disruption of Endogenous Purinergic Signaling Inhibits Vascular Endothelial Growth Factor- and Glutamate-Induced Osmotic Volume Regulation of Müller Glial Cells in Knockout Mice
Authors: Grosche Antje , Pannicke Thomas , Chen Ju , Wiedemann Peter , Reichenbach Andreas , Bringmann Andreas
Published: September 2013

Background/Aims: Osmotic swelling of Müller cells is a common phenomenon in animal models of ischemic and diabetic retinopathies. Müller cells possess a swelling-inhibitory purinergic signaling cascade which can be activated by various receptor ligands including vascular endothelial growth factor (VEGF) and glutamate. Here, we investigated whether deletion of P2Y1 (P2Y1R) and adenosine A1 receptors (A1AR), and of inositol-1,4,5-trisphosphate-receptor type 2 (IP3R2), in mice affects the inhibitory action of VEGF and glutamate on Müller cell swelling. Methods: The cross-sectional area of Müller cell somata was recorded after a 4-min superfusion of retinal slices with a hypoosmotic solution. Results: Hypoosmolarity induced a swelling of Müller cells from P2Y1R-/-, A1AR-/- and IP3R2-/- mice, but not from wild-type mice. Swelling of wild-type Müller cells was induced by hypoosmotic solution containing barium chloride. Whereas VEGF inhibited the swelling of wild-type Müller cells, it had no swelling-inhibitory effect in cells from A1AR-/- and IP3R2-/- mice. Glutamate inhibited the swelling of wild-type Müller cells but not of cells from P2Y1R-/-, A1AR-/- and IP3R2-/- animals. Conclusion: The swelling-inhibitory effects of VEGF and glutamate in murine Müller cells is mediated by transactivation of P2Y1R and A1AR, as well as by intracellular calcium signaling via activation of IP3R2.
Impact of Erythropoietin on Intensive Care Unit Patients
Authors: Jelkmann Ines , Jelkmann Wolfgang
Published: September 2013

Anemia is common in intensive care unit (ICU) patients. Red blood cell (RBC) transfusions are mainstays of their treatment and can be life-saving. Allogeneic blood components inherently bear risks of infection and immune reactions. Although these risks are rare in developed countries, recombinant human erythropoietin (rhEpo) and other erythropoiesis-stimulating agents (ESAs) have been considered alternative anti-anemia treatment options. As summarized herein, however, most of the clinical studies suggest that ESAs are not usually advisable in ICU patients unless approved indications exist (e.g., renal disease). First, ESAs act in a delayed way, inducing an increase in reticulocytes only after a lag of 3-4 days. Second, many critically ill patients present with ESA resistance as inflammatory mediators impair erythropoietic cell proliferation and iron availability. Third, the ESA doses used for treatment of ICU patients are very high. Fourth, ESAs are not legally approved for general use in ICU patients. Solely in distinct cases, such as Jehovah's Witnesses who refuse allogeneic blood transfusions due to religious beliefs, ESAs may be considered an exceptional therapy.
Aortic Valve Stenosis and Atrial Fibrillation Influence Plasma Fibulin-1 Levels in Patients Treated with Coronary Bypass Surgery
Authors: Hansen Maria Lyck , Dahl Jordi S. , Argraves W. Scott , Irmukhamedov Akhmadjon , Rasmussen Lars Melholt
Published: September 2013

Objectives: Aortic valve stenosis (AS) causes cardiac fibrosis and left ventricular hypertrophy, and over time heart failure can occur. To date, a reliable marker to predict progression of AS or the development of heart failure is still lacking. In this study, we addressed the hypothesis that fibulin-1 levels reflect myocardial fibrosis. Methods: Patients undergoing heart surgery at the Odense University were investigated. By 2012 data on outcome were obtained. Results: In 293 patients, plasma fibulin-1 levels were measured. Patients with AS or atrial fibrillation (AF) had significantly higher fibulin-1 levels compared to those with coronary artery disease only (p = 0.005). Patients with preoperatively diagnosed chronic AF had significantly higher levels of fibulin-1 compared to those without (p = 0.004). Plasma fibulin-1 levels showed no relationship to echocardiographic size and had no impact on outcome, death or other adverse events. Conclusion: This study shows that plasma fibulin-1 levels are increased in patients with AS and AF compared to patients with coronary disease only. Our study results suggest fibulin-1, a vascular extracellular matrix (ECM) protein, as a marker of ECM turnover perhaps due to the increased myocardial stretch that is related to pressure overload.
Creativity, Alcohol and Drug Abuse: The Pop Icon Jim Morrison
Authors: Holm-Hadulla Rainer M. , Bertolino Alina
Published: September 2013

Background: Alcohol and drug abuse is frequent among performers and pop musicians. Many of them hope that alcohol and drugs will enhance their creativity. Scientific studies are scarce and conclusions limited for methodological reasons. Furthermore, extraordinary creativity can hardly be grasped by empirical-statistical methods. Thus, ideographic studies are necessary to learn from extraordinarily creative persons about the relationship of creativity with alcohol and drugs. The pop icon Jim Morrison can serve as an exemplary case to investigate the interrelation between alcohol and drug abuse and creativity. Methods: Morrison's self-assessments in his works and letters as well as the descriptions by others are analyzed under the perspective of creativity research. Results: In the lyrics of Jim Morrison and in biographical descriptions, we can see how Jim Morrison tried to cope with traumatic events, depressive moods and uncontrolled impulses through creative activities. His talent, skill and motivation to write creatively were independent from taking alcohol and drugs. He used alcohol and drugs to transgress restrictive social norms, to broaden his perceptions and to reinforce his struggle for self-actualization. In short, his motivation to create something new and authentic was reinforced by alcohol and drugs. More important was the influence of a supportive group that enabled Morrison's talents to flourish. However, soon the frequent use of high doses of alcohol and drugs weakened his capacity to realize creative motivation. Conclusions: Jim Morrison is an exemplary case showing that heavy drinking and the abuse of LSD, mescaline and amphetamines damages the capacity to realize creative motivation. Jim Morrison is typical of creative personalities like Amy Winehouse, Janis Joplin, Brian Jones and Jimmy Hendrix who burn their creativity in early adulthood through alcohol and drugs. We suppose that the sacrificial ritual of their decay offers some benefits for the excited spectators. One of these is the illusion that alcohol and drugs can lead to authenticity and creativity.
Endoscopic Laser Dichorionization of the Placenta in the Treatment of Severe Twin-Twin Transfusion Syndrome
Authors: Peralta Cleisson F.A. , Molina Francisca S. , Gómez Luisa F. , Bennini João R. , Gomes Neto Orlando , Barini Ricardo
Published: September 2013

Objectives: To describe the results of a technique of laser ablation of placental vessels in the treatment of severe twin-twin transfusion syndrome (TTTS), which is characterized by separation of the fetoplacental vascular territories and dichorionization of the placenta. Patients and Methods: Descriptive analysis of TTTS cases treated with the endoscopic laser dichorionization of the placenta (ELDP) procedure. The variables evaluated were the occurrence of reversal of the donor-recipient phenotype, persistence of TTTS or twin anemia-polycythemia sequence (TAPS); gestational age at delivery; discharge from the hospital of at least 1 or 2 live neonates, and incidence of neurological alterations among survivors. Results: 67 patients were treated with the ELDP procedure. There was no persistence of TTTS, reversal of the donor-recipient phenotype or TAPS. The median gestational age at delivery was 33.0 (23.6-37.7) weeks. The rate of discharge from the hospital of at least 1 or 2 live neonates was 88.2% (67/76) and 71.1% (54/76), respectively. Among survivors, 17 (17/121 = 14.0%) children presented with neurodevelopmental alterations during clinical follow-up. Conclusions: The major contribution of this study was the demonstration that the ELDP technique appears to be associated with a low risk of persistence or recurrence of TTTS and TAPS.