bluuebunny/crossref_metadata_2025 huggingface dataset:
Where do young men want to access STI screening? A stratified random probability sample survey of young men in Great Britain
Authors: Saunders John M , Mercer Catherine H , Sutcliffe Lorna J , Hart Graham J , Cassell Jackie , Estcourt Claudia S
Published: April 2012

Objectives

Rates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport.

Methods

A stratified random probability survey of 411 (weighted n=632) men in Great Britain aged 18–35 years using computer-assisted personal and self-interviews.

Results

Young men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%).

Conclusions

Healthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.
THE ELECTRONIC CORRELATION EFFECT FROM WEAK TO STRONG IN THE THREE DIMENSIONAL ELECTRON GAS
Authors: YU ZHI-MING , WANG QING-WEI , LIU YU-LIANG
Published: April 2012

Based on the success of the eigenfunctional theory ( EFT) in the one-dimensional model,16,24,51 we apply it to the three-dimensional homogeneous electron gas. By EFT, we first present a rigorous expression of the pair distribution function g(r) of the electron gas. This expression effectively solves the negative problem of g(r) that when electronic correlation effect is strong, the previous theories give a negative g(r),9 while g(r) is strictly a positive function. From this reasonable g(r), we estimate and establish a newly effective fitting expression of the ground state energy of electron gas. The new fitting expression presents a similar result with present theories when rs is small, since only in the limit of rs is small, present theories estimate a exact ground state energy. When rs increases, the difference between EFT and other theories becomes more and more remarkable. The difference is expected as EFT estimates a reasonable g(r) and would effectively amend the overestimate of previous theories in the ground state energy. In addition, by the ground state energy, we estimate the phase transition derived by the strong correlation effect. When the density decreases, the electronic correlation effect changes from weak to strong and we observe a sudden phase transition from paramagnetic to full spin polarization occurring at rs = 31 ± 4.
ON BOUNDING MEASURES OF PRIMENESS IN INTEGRAL DOMAINS
Authors: ANDERSON DAVID F. , CHAPMAN SCOTT T.
Published: April 2012

Let D be an integral domain. In this paper, we investigate two (integer- or ∞-valued) invariants ω(D, x) and ω(D) which measure how far a nonzero x ∈ D is from being prime and how far an atomic integral domain D is from being a unique factorization domain (UFD), respectively. In particular, we are interested in when there is a nonzero (irreducible) x ∈ D with ω(D, x) = ∞ and the relationship between ω(A, x) and ω(B, x), and ω(A) and ω(B), for an extension A ⊆ B of integral domains and a nonzero x ∈ A.
FREE GROUP ALGEBRAS IN DIVISION RINGS
Authors: GONÇALVES J. Z. , TENGAN E.
Published: April 2012

Let k be an algebraically closed field of characteristic zero and let L be an algebraic function field over k. Let σ : L → L be a k-automorphism of infinite order, and let D be the skew field of fractions of the skew polynomial ring L[t; σ]. We show that D contains the group algebra kF of the free group F of rank 2.
NEUTRON RICH NUCLEI IN A NEW BINDING ENERGY FORMULA AND THE ASTROPHYSICAL r-PROCESS
Authors: LAHIRI CHIRASHREE , GANGOPADHYAY G.
Published: April 2012

Neutron rich nuclei has been studied with a new phenomenological mass formula. Predictions of different mass formulas for the location of the neutron drip line are compared with those from the present calculation. The implications of the new mass formula for r-process nucleosynthesis are discussed. It is found that though the neutron drip line obtained from this formula differs substantially from other formulas, the r-process abundance upto mass 200 are unlikely to be significantly different. The errors inherent in the mass formula are found to play an insignificant role beyond mass A = 80.
DYNAMIC RESPONSE OF METALLIC SANDWICH PANELS UNDER BLAST LOADINGS
Authors: WANG HONGXIN , ZHA XIAOXIONG , YE JIANQIAO
Published: April 2012

An energy-balance-based analytical method and finite element (FE) simulations were developed in this paper to study the dynamic response of metallic sandwich panels subject to blast loadings. The analytical model can be used to predict approximately the deflection of the panels, while the FE model can take into account fluid–structure interactions and the effect of strain rate. Both models were validated by comparing their predictions with the test results available in the literature. Parametric studies were then carried out to assess various factors that are influential in characterizing the dynamic behavior of sandwich panels subject to blast loads.
ON THE INSTABILITY OF SPINNING CYLINDRICAL SHELLS PARTIALLY FILLED WITH LIQUID
Authors: FIROUZ-ABADI R. D. , PERMOON M. R. , HADDADPOUR H.
Published: April 2012

The dynamics and stability of rotating circular cylindrical shells partially filled with ideal liquid is analyzed. The structural dynamics of the shell is modeled by using the first-order shear deformable shell theory and the flow inside the cylinder is simulated by a quasi 2D model based on the Navier–Stokes equations for ideal liquid. The fluid and structural models are combined using the nonpenetration condition of the flow on the wetted surface of the cylinder and the fluid pressure on the flexible shell. The obtained fluid–structure model is employed for the determination of the stable regions of the spinning frequency of the cylinder. A series of case studies are performed on the governing parameters of the instability of the cylinder and some conclusions are outlined.
3D ACOUSTIC SHAPE SENSITIVITY ANALYSIS USING FAST MULTIPOLE BOUNDARY ELEMENT METHOD
Authors: ZHENG C. J. , CHEN H. B. , MATSUMOTO T. , TAKAHASHI T.
Published: April 2012

This paper presents a fast multipole boundary element approach to the 3D acoustic shape sensitivity analysis based on the discrete adjoint variable method. The Burton–Miller formula is used to conquer the fictitious eigenfrequency problem of the original boundary integral equation method in solving exterior acoustic problems. Constant elements are used to discretize the boundary, so that the hypersingular integrals contained in the formulae can be evaluated explicitly and directly. Numerical examples are presented to demonstrate the accuracy and efficiency of the present approach.
A SOLVER OF LINEAR SYSTEMS OF EQUATIONS (REBSM) FOR LARGE-SCALE ENGINEERING PROBLEMS
Authors: GAO XIAO-WEI , LI LINGJIE
Published: April 2012

In this paper, a novel linear equation solution method is proposed based on a row elimination back-substitution method (REBSM). The elimination and back-substitution procedures are carried out on individual row levels. The advantage of the proposed method is that it is much faster and requires less storage than the Gaussian elimination algorithm and, therefore, is capable of solving larger systems of equations. The method is particularly efficient for solving band diagonal sparse systems with symmetric or nonsymmetric coefficient matrices, and can be easily applied to popular numerical methods, such as the finite element method and the boundary element method. Detailed Fortran codes and examples are given to demonstrate the robustness and efficiency of the proposed method.
GLOBAL STABILITY OF A STAGE-STRUCTURED PREDATOR–PREY MODEL WITH MODIFIED LESLIE–GOWER AND HOLLING-TYPE II SCHEMES
Authors: LI ZHONG , HAN MAOAN , CHEN FENGDE
Published: April 2012

In this paper, we consider a stage-structured predator–prey model with modified Leslie–Gower and Holling-type II schemes. Using an iterative technique, we investigate the global stability of the positive equilibrium of the system. Finally, some examples are presented to verify our main result.
Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats
Authors: Reidelberger Roger , Haver Alvin , Chelikani Prasanth K. , Apenteng Bettye , Perriotte-Olson Curtis , Anders Krista , Steenson Sharalyn , Blevins James E.
Published: April 2012

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg−1·h−1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg−1·h−1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats.
Stress is a critical player inCYP3A,CYP2C, andCYP2Dregulation: role of adrenergic receptor signaling pathways
Authors: Daskalopoulos Evangelos P. , Malliou Foteini , Rentesi Georgia , Marselos Marios , Lang Matti A. , Konstandi Maria
Published: April 2012

Stress is a critical player in the regulation of the major cytochrome P-450s ( CYPs) that metabolize the majority of the prescribed drugs. Early in life, maternal deprivation (MD) stress and repeated restraint stress (RS) modified CYP expression in a stress-specific manner. In particular, the expression of CYP3A1 and CYP2C11 was increased in the liver of MD rats, whereas RS had no significant effect. In contrast, hepatic CYP2D1/2 activity was increased by RS, whereas MD did not affect it. The primary effectors of the stress system, glucocorticoids and epinephrine, highly induced CYP3A1/2. Epinephrine also induced the expression of CYP2C11 and CYP2D1/2. Further investigation indicated that AR-agonists may modify CYP regulation. In vitro experiments using primary hepatocyte cultures treated with the AR-agonists phenylephrine, dexmedetomidine, and isoprenaline indicated an AR-induced upregulating effect on the above-mentioned CYPs mediated by the cAMP/protein kinase A and c-Jun NH2-terminal kinase signaling pathways. Interestingly though, in vivo pharmacological manipulations of ARs using the same AR-agonists led to a suppressed hepatic CYP expression profile, indicating that the effect of the complex network of central and peripheral AR-linked pathways overrides that of the hepatic ARs. The AR-mediated alterations in CYP3A1/2, CYP2C11, and CYP2D1/2 expressions are potentially connected with those observed in the activation of signal transducer and activator of transcription 5b. In conclusion, stress and AR-agonists may modify the expression of the major CYP genes involved in the metabolism of drugs used in a wide range of diseases, thus affecting drug efficacy and toxicity.
Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects
Authors: Jensen Jørgen , Tantiwong Puntip , Stuenæs Jorid T. , Molina-Carrion Marjorie , DeFronzo Ralph A. , Sakamoto Kei , Musi Nicolas
Published: April 2012

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇o2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS Kmfor UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50–70% (Ser641, Ser645, and Ser645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser7phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased Kmfor UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.
Entrainment of peripheral clock genes by cortisol
Authors: Mavroudis Panteleimon D. , Scheff Jeremy D. , Calvano Steve E. , Lowry Stephen F. , Androulakis Ioannis P.
Published: April 2012

Circadian rhythmicity in mammals is primarily driven by the suprachiasmatic nucleus (SCN), often called the central pacemaker, which converts the photic information of light and dark cycles into neuronal and hormonal signals in the periphery of the body. Cells of peripheral tissues respond to these centrally mediated cues by adjusting their molecular function to optimize organism performance. Numerous systemic cues orchestrate peripheral rhythmicity, such as feeding, body temperature, the autonomic nervous system, and hormones. We propose a semimechanistic model for the entrainment of peripheral clock genes by cortisol as a representative entrainer of peripheral cells. This model demonstrates the importance of entrainer's characteristics in terms of the synchronization and entrainment of peripheral clock genes, and predicts the loss of intercellular synchrony when cortisol moves out of its homeostatic amplitude and frequency range, as has been observed clinically in chronic stress and cancer. The model also predicts a dynamic regime of entrainment, when cortisol has a slightly decreased amplitude rhythm, where individual clock genes remain relatively synchronized among themselves but are phase shifted in relation to the entrainer. The model illustrates how the loss of communication between the SCN and peripheral tissues could result in desynchronization of peripheral clocks.
Blood Rheology and Platelet Function in Untreated Early-Stage Essential Hypertensives Complicated with Metabolic Syndrome
Authors: Sugimori Hiroko , Tomoda Fumihiro , Koike Tsutomu , Kinuno Hiroyuki , Kurosaki Hiroko , Masutani Toshitaka , Inoue Hiroshi
Published: April 2012

We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index “k” did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity.
Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma
Authors: Onuchic Ana Claudia , Machado Camila M. L. , Saito Renata F. , Rios Francisco J. , Jancar Sônia , Chammas Roger
Published: April 2012

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cellsin vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.
Emotional Intelligence: An Untapped Resource for Alcohol and Other Drug Related Prevention among Adolescents and Adults
Authors: Coelho Ken Russell
Published: April 2012

Alcohol and Other Drug abuse in adolescents and adults continues to be a major public health problem in the United States. Care in intervention programs aimed at high risk populations identified occurs after the maladaptive behavioral delinquency has occurred, and only then is an individual afforded the opportunity to join an intervention program. The focus of this paper is to illustrate and highlight the value of prevention programs which emphasize altering maladaptive behavior before the behavior becomes problematic. Emotional Intelligence is not only an indicator of alcohol and other drug abuse, but is linked to emotional competence, social and emotional learning, the development of healthy and life promoting behavior, and has been proven to reduce some of the risk factors associated with alcohol and other drug abuse in adolescents and adults. This paper seeks to recognize the significance of Emotional Intelligence as a desirable health promoting attribute and to establish the importance of its conceptual use in a prevention based model for reducing associated high risk behaviors.
PseudacteonParasitoids ofAzteca instabilisAnts in Southern Mexico (Diptera: Phoridae; Hymenoptera: Formicidae)
Authors: Brown Brian V. , Philpott Stacy M.
Published: April 2012

Three new species of the genusPseudacteonare described, all from Chiapas, Mexico, and all of which are parasitoids of the antAzteca instabilis. Sternite 6 ofPseudacteon dorymyrmecisBorgmeier is illustrated for the first time, andP. confususDisney is synonymized with this species. The natural history of theAzteca-Pseudacteoninteraction is described.
Minimum Total Noise in Wave-Mixing Processes
Authors: Gill Savita , Rani Sunil , Singh Nafa
Published: April 2012

Higher-order squeezing in different optical processes such as seven-wave mixing and five-wave mixing has been studied. The total noise of a field state is a measure of the fluctuations of the field amplitude. It is shown that the minimum total noise (Tmin) of a higher-order squeezed state always increases with the increase in nonclassicality associated with higher-order squeezing. Thus, fromTmin, one can conclude that highly nonclassical states have large amplitude fluctuations.
Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
Authors: Wang Chun , Fu Ruiling , Chen Zhenhua , Tan Kun , Chen Lingxia , Teng Xindong , Lu Jia , Shi Chunwei , Fan Xionglin
Published: April 2012

Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) ofMycobacterium tuberculosiswere constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG containing empty vector pMV261(rBCG::261), which had low levels of endogenous expression of both proteins as expected. rBCG::AB strain could provide the strongest short-term and long-term protection in the lung against intravenous infection with virulentM. tuberculosisthan rBCG::261 control and other two rBCG strains overexpressing single antigen. The stronger and longer-lasting protection provided by rBCG::AB than rBCG::261 was correlated with systemicin vitroantigen-specific IFN-γresponses. Therefore, our results indicate that rBCG::AB could be a very promising TB vaccine candidate and should be further evaluated for the preclinical test.
Frequency-Dependent Streaming Potentials: A Review
Authors: Jouniaux L. , Bordes C.
Published: April 2012

The interpretation of seismoelectric observations involves the dynamic electrokinetic coupling, which is related to the streaming potential coefficient. We describe the different models of the frequency-dependent streaming potential, mainly Packard's and Pride's model. We compare the transition frequency separating low-frequency viscous flow and high-frequency inertial flow, for dynamic permeability and dynamic streaming potential. We show that the transition frequency, on a various collection of samples for which both formation factor and permeability are measured, is predicted to depend on the permeability as inversely proportional to the permeability. We review the experimental setups built to be able to perform dynamic measurements. And we present some measurements and calculations of the dynamic streaming potential.
Ophthalmic Disorders in Adults with Down Syndrome
Authors: Krinsky-McHale Sharon J. , Jenkins Edmund C. , Zigman Warren B. , Silverman Wayne
Published: April 2012

A myriad of ophthalmic disorders is associated with the phenotype of Down syndrome including strabismus, cataracts, and refractive errors potentially resulting in significant visual impairment. Ophthalmic sequelae have been extensively studied in children and adolescents with Down syndrome but less often in older adults. In-depth review of medical records of older adults with Down syndrome indicated that ophthalmic disorders were common. Cataracts were the most frequent ophthalmic disorder reported, followed by refractive errors, strabismus, and presbyopia. Severity of intellectual disability was unrelated to the presence of ophthalmic disorders. Also, ophthalmic disorders were associated with lower vision-dependent functional and cognitive abilities, although not to the extent that was expected. The high prevalence of ophthalmic disorders highlights the need for periodic evaluations and individualized treatment plans for adults with Down syndrome, in general, but especially when concerns are identified.
MEK1/2 Inhibition Elicits Regression of Autochthonous Lung Tumors Induced by KRASG12D or BRAFV600E
Authors: Trejo Christy L. , Juan Joseph , Vicent Silvestre , Sweet-Cordero Alejandro , McMahon Martin
Published: April 2012

Genetically engineered mouse (GEM) models of lung tumorigenesis allow careful evaluation of lung tumor initiation, progression, and response to therapy. Using GEM models of oncogene-induced lung cancer, we show the striking similarity of the earliest stages of tumorigenesis induced by KRASG12D or BRAFV600E. Cre-mediated expression of KRASG12D or BRAFV600E in the lung epithelium of adult mice initially elicited benign lung tumors comprising cuboidal epithelial cells expressing markers of alveolar pneumocytes. Strikingly, in a head-to-head comparison, oncogenic BRAFV600E elicited many more such benign tumors and did so more rapidly than KRASG12D. However, despite differences in the efficiency of benign tumor induction, only mice with lung epithelium expression of KRASG12D developed malignant non–small cell lung adenocarcinomas. Pharmacologic inhibition of mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK)1/2 combined with in vivo imaging showed that initiation and maintenance of both BRAFV600E- or KRASG12D-induced lung tumors was dependent on MEK→ERK signaling. Although the tumors dramatically regressed in response to MEK1/2 inhibition, they regrew following cessation of drug treatment. Together, our findings show that RAF→MEK→ERK signaling is both necessary and sufficient for KRASG12D-induced benign lung tumorigenesis in GEM models. The data also emphasize the ability of KRASG12D to promote malignant lung cancer progression compared with oncogenic BRAFV600E. Cancer Res; 72(12); 3048–59. ©2012 AACR.
Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples
Authors: Bertilsson Helena , Tessem May-Britt , Flatberg Arnar , Viset Trond , Gribbestad Ingrid , Angelsen Anders , Halgunset Jostein
Published: April 2012

Purpose: Low concentrations of citrate and high concentrations of choline-containing compounds (ChoCC) are metabolic characteristics observed by magnetic resonance spectroscopy of prostate cancer tissue. The objective was to investigate the gene expression changes underlying these metabolic aberrations to find regulatory genes with potential for targeted therapies.

Experimental design: Fresh frozen samples (n = 133) from 41 patients undergoing radical prostatectomy were included. Histopathologic evaluation was carried out for each sample before a metabolic profile was obtained with high-resolution magic angle spinning (HR-MAS) spectroscopy. Following the HR-MAS, RNA was extracted from the same sample and quality controlled before carrying out microarray gene expression profiling. A partial least square statistical model was used to integrate the data sets to identify genes whose expression show significant covariance with citrate and ChoCC levels.

Results: Samples were classified as benign, n = 35; cancer of low grade (Gleason score 6), n = 24; intermediate grade (Gleason score 7), n = 41; or high grade (Gleason score ≥8), n = 33. RNA quality was high with a mean RNA Integrity Number score of 9.1 (SD 1.2). Gene products predicting significantly a reduced citrate level were acetyl citrate lyase (ACLY, P = 0.003) and m-aconitase (ACON, P < 0.001). The two genes whose expression most closely accompanied the increase in ChoCC were those of phospholipase A2 group VII (PLA2G7, P < 0.001) and choline kinase α (CHKA, P = 0.002).

Conclusions: By integrating histologic, transcriptomic, and metabolic data, our study has contributed to an expanded understanding of the mechanisms underlying aberrant citrate and ChoCC levels in prostate cancer. Clin Cancer Res; 18(12); 3261–9. ©2012 AACR.
Safety and Pharmacokinetics of Ganitumab (AMG 479) Combined with Sorafenib, Panitumumab, Erlotinib, or Gemcitabine in Patients with Advanced Solid Tumors
Authors: Rosen Lee S. , Puzanov Igor , Friberg Gregory , Chan Emily , Hwang Yuying C. , Deng Hongjie , Gilbert Jill , Mahalingam Devalingam , McCaffery Ian , Michael Shaunita A. , Mita Alain C. , Mita Monica M. , Mulay Marilyn , Shubhakar Poornima , Zhu Min , Sarantopoulos John
Published: April 2012

Purpose: This phase 1b dose-escalation study assessed safety, tolerability, and pharmacokinetics of ganitumab, a fully human monoclonal antibody against the insulin-like growth factor 1 (IGF1) receptor, combined with targeted agents or cytotoxic chemotherapy in patients with advanced solid tumors.

Experimental Design: Patients with treatment-refractory advanced solid tumors were sequentially enrolled at 2 ganitumab dose levels (6 or 12 mg/kg i.v. every 2 weeks) combined with either sorafenib 400 mg twice daily, panitumumab 6 mg/kg every 2 weeks, erlotinib 150 mg once daily, or gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of each 4-week cycle. The primary end points were safety and pharmacokinetics of ganitumab.

Results: Ganitumab up to 12 mg/kg appeared well tolerated combined with sorafenib, panitumumab, erlotinib, or gemcitabine. Treatment-emergent adverse events were generally mild and included fatigue, nausea, vomiting, and chills. Three patients had dose-limiting toxicities: grade 3 hyperglycemia (ganitumab 6 mg/kg and panitumumab), grade 4 neutropenia (ganitumab 6 mg/kg and gemcitabine), and grade 4 thrombocytopenia (ganitumab 12 mg/kg and erlotinib). Ganitumab-binding and panitumumab-binding antibodies were detected in 5 and 2 patients, respectively; neutralizing antibodies were not detected. The pharmacokinetics of ganitumab and each cotherapy did not appear affected by coadministration. Circulating total IGF1 and IGF binding protein 3 increased from baseline following treatment. Four patients (9%) had partial responses.

Conclusions: Ganitumab up to 12 mg/kg was well tolerated, without adverse effects on pharmacokinetics in combination with either sorafenib, panitumumab, erlotinib, or gemcitabine. Ganitumab is currently under investigation in combination with some of these and other agents. Clin Cancer Res; 18(12); 3414–27. ©2012 AACR.
Risk Factors for Dementia in a Senegalese Elderly Population Aged 65 Years and Over
Authors: Toure K. , Coume M. , Ndiaye M. , Zunzunegui M.V. , Bacher Y. , Diop A.G. , Ndiaye M.M.
Published: April 2012

Background: With the aging of the population, dementia is increasing worldwide. The objective of this study was to identify risk factors for dementia in an elderly population utilizing a primary health care service in Dakar, Senegal. Methods: Through a cross-sectional study conducted from March 2004 to December 31, 2005, 507 elderly patients aged ≥65 years who came to the Social and Medical Center of IPRES, Dakar, Senegal, were first screened with the screening interview questionnaire ‘Aging in Senegal’. Those who were cognitively impaired underwent a clinical examination to detect dementia. Univariate, bivariate, and multivariate logistic regression analyses were done. Results: The whole population had a mean age of 72.4 years (±5.2) and was mostly male, married, and non-educated. Hypertension, arthritis, and gastrointestinal diseases were the main health conditions reported in the past medical history. Smoking was important while alcohol consumption was rare. Social network was high. Forty-five patients (8.87%) had dementia. In the multivariate model, only advanced age, education, epilepsy, and family history of dementia were independently associated with dementia. Conclusion: The risk factors identified are also found in developed countries confirming their role in dementia. It is important to take dementia into consideration in Senegal and to sensitize the community for prevention.
A 26-Year Review of Emergency Peripartum Hysterectomy in a Tertiary Teaching Hospital in Kuwait – Years 1983–2011
Authors: Chibber Rachana , Al-Hijji Jassim , Fouda Mohamed , Al-Saleh Eyad , Al-Adwani Abdul Razzak , Mohammed Asiya Tasneem
Published: April 2012

Objective: To identify the risk factors and study the incidence, indications and complications of emergency peripartum hysterectomy (EPH). Materials and Methods: This was a retrospective case-control study. The cases consisted of all women who underwent EPH between January 1983 and January 2011. Two controls per case were randomly selected from the remaining deliveries by using a random number table. Case records were retrieved from the medical records. Results: Among 150,993 deliveries, there were 59 EPHs (cases), giving a rate of 0.390 per 1,000. Of the 59 cases, only 56 were analysed because 3 files were unavailable. These women were older (mean age 36 ± 5.7 vs. 22 ± 5.3 years, p < 0.01) and had delivered more than 1 child (p = 0.02). Thirty-seven (66%) cases had had previous caesarean sections (CSs) and the number of CSs in this group was greater than in the controls (21%, p < 0.01). More index cases had a history of atonic postpartum haemorrhage (46 vs. 4%, p < 0.001) and placenta praevia (34 vs. 4%, p < 0.01). More cases than controls were delivered by CS (73 vs. 29%; p = 0.003). The leading indications for EPH were haemorrhage due to uterine atony and placenta praevia. Independent risk factors were older age, multiparity, history of one or more CSs and placenta praevia. There were 2 maternal deaths from coagulopathy following massive obstetric haemorrhage. The main complications of EPH were febrile morbidity: 12 (21%), wound infection: 8 (14%) and bladder or ureteric injury: 8 (14%). Conclusions: CSs, especially repeat CSs in women with placenta praevia and persistent uterine atony, significantly increased the risks of peripartum hysterectomy.
Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina
Authors: Januschowski Kai , Maddani Ramin , Mueller Sebastian , Lueke Matthias , Spitzer Martin S. , Schultheiss Maximilian , Bartz-Schmidt Karl-Ulrich , Szurman Peter
Published: April 2012

Purpose: To compare the effect of a taurine-containing intraocular irrigation solution (PuriProtect™) to a standard irrigation solution (BSS™) we evaluated the retinal function using an electroretinogram (ERG) and analyzed the survival of retinal ganglion cells on isolated whole mount retinas. Materials and Methods: During ERG recordings, each irrigation solution was superfused for 45 min with the relevant irrigation solution. To investigate the effects on photoreceptor function, 1 mM asparate was added to obtain a-waves. The recovery of the a- and b-wave was monitored after superfusing the retinas with standard medium again. To evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4°C in darkness and after staining the retinas with ethidium homodimer-1 the retinas were analyzed using fluorescence microscopy. Results: The application of standard medium supplemented with 2 mM taurine resulted in a significant increase of the b-wave amplitude compared to standard medium alone. The a-wave amplitudes showed no significant changes under taurine supplementation. Compared to standard medium BSS showed no significant decrease in b-wave amplitudes, but a significant decrease in a-wave amplitudes. In contrast to BSS there were no significant changes in the a- or b-wave amplitudes detectable after the application of PuriProtect. At the end of the washout period no significant changes in a- or b-wave amplitudes were recorded for any tested irrigation solution. Retinas stored for 24 h in PuriProtect or in standard medium with taurine had a statistically significant smaller amount of dead cells than retinas stored in standard medium without taurine supplementation. Conclusions: BSS does not seem to be an ideal irrigation solution, because it compromises the a-wave in the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG and showed a better long-term effect on ganglion cell survival. Taurine supplementation, therefore, seems to be neuroprotective and its supplementation to an intraocular irrigation solution favorable for the retina.
Effect of L-Arginine and Selenium Added to a Hypocaloric Diet Enriched with Legumes on Cardiovascular Disease Risk Factors in Women with Central Obesity: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Alizadeh Mohammad , Safaeiyan Abdolrasoul , Ostadrahimi Alireza , Estakhri Rassul , Daneghian Sevana , Ghaffari Aida , Gargari Bahram Pourghassem
Published: April 2012

Background/Aims: We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. Methods: This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 µg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. Results: After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NOx), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NOx. HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. Conclusion: These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NOx and TG.
Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations
Authors: Hooghiemstra Astrid M. , Eggermont Laura H.P. , Scheltens Philip , van der Flier Wiesje M. , Scherder Erik J.A.
Published: April 2012

Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD) are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.
Eleven Years’ Experience with Korean Cardiac Myxoma Patients: Focus on Embolic Complications
Authors: Lee Seung-Jae , Kim Jae-Hyun , Na Chan-Young , Oh Sam-Sae
Published: April 2012

Background: Cardiac myxomas are rare but are the most common cardiac tumors. This study is based on our clinical experience with cardiac myxomas over a period of 11 years at Sejong General Hospital. We focused on the embolic complications of patients with cardiac myxoma. Methods: We retrospectively reviewed the medical records of 59 consecutive patients with cardiac myxoma who were treated between January 2000 and March 2011. The myxomas were divided into two types: type 1, with an irregular or villous surface and a soft consistency, and type 2, with a smooth surface and a compact consistency. The 59 investigated patients were classified into the embolic group and the non-embolic group. Results: Cardiac obstructive symptoms, embolic events and constitutional symptoms were observed in 37 (62.7%), 13 (22.0%) and 10 (16.9%) patients, respectively. When the embolic and non-embolic groups were compared, there were no significant differences in vascular risk factors, the ejection fraction, the left atrial diameter or the tumor size. However, type 1 myxomas were significantly more frequent in the embolic group (p = 0.009 by Fisher’s exact test). A binary logistic regression analysis showed that type 1 pathology alone was independently associated with myxoma-related embolism (p = 0.008; odds ratio 10.056; 95% confidence interval 1.828–55.337). There were no operative deaths in any of the 59 patients studied. Among the 13 patients with embolism, 11 (84.6%) had brain infarcts. The main patterns of the lesions were multiple lesions (8 out of 11 patients, 72.7%) and lesions in the middle cerebral artery territories (7 out of 11 patients, 63.6%). The other 2 patients were found to have occlusion of the left central retinal artery and left external iliac artery. Additionally, incidental cerebral aneurysms were found in the latter case. There was no recurrence of myxoma or myxoma-related symptoms in the 53 patients receiving outpatient management during the follow-up period (range 2 months to 11 years). Conclusions: The embolic potential of myxoma was associated with an irregular surface pathology but not with vascular risk factors. Echocardiography should be performed in patients with embolic events, especially when cerebral infarcts with multiple territorial lesions are detected. Surgical resection is a relatively safe and curative procedure for cardiac myxoma.
Granulocyte Colony-Stimulating Factor Improves Cerebrovascular Reserve Capacity by Enhancing Collateral Growth in the Circle of Willis
Authors: Duelsner André , Gatzke Nora , Glaser Johanna , Hillmeister Philipp , Li Meijing , Lee Eun-Ji , Lehmann Kerstin , Urban Daniel , Meyborg Heike , Stawowy Philipp , Busjahn Andreas , Nagorka Stephanie , Bondke Persson Anja , Buschmann Ivo R.
Published: April 2012

Background and Purpose: Restoration of cerebrovascular reserve capacity (CVRC) depends on the recruitment and positive outward remodeling of preexistent collaterals (arteriogenesis). With this study, we provide functional evidence that granulocyte colony-stimulating factor (G-CSF) augments therapeutic arteriogenesis in two animal models of cerebral hypoperfusion. We identified an effective dosing regimen that improved CVRC and stimulated collateral growth, thereby improving the outcome after experimentally induced stroke. Methods: We used two established animal models of (a) cerebral hypoperfusion (mouse, common carotid artery ligation) and (b) cerebral arteriogenesis (rat, 3-vessel occlusion). Following therapeutic dose determination, both models received either G-CSF, 40 µg/kg every other day, or vehicle for 1 week. Collateral vessel diameters were measured following latex angiography. Cerebrovascular reserve capacities were assessed after acetazolamide stimulation. Mice with left common carotid artery occlusion (CCAO) were additionally subjected to middle cerebral artery occlusion, and stroke volumes were assessed after triphenyltetrazolium chloride staining. Given the vital role of monocytes in arteriogenesis, we assessed (a) the influence of G-CSF on monocyte migration in vitro and (b) monocyte counts in the adventitial tissues of the growing collaterals in vivo. Results: CVRC was impaired in both animal models 1 week after induction of hypoperfusion. While G-CSF, 40 µg/kg every other day, significantly augmented cerebral arteriogenesis in the rat model, 50 or 150 µg/kg every day did not show any noticeable therapeutic impact. G-CSF restored CVRC in mice (5 ± 2 to 12 ± 6%) and rats (3 ± 4 to 19 ± 12%). Vessel diameters changed accordingly: in rats, the diameters of posterior cerebral arteries (ipsilateral: 209 ± 7–271 ± 57 µm; contralateral: 208 ± 11–252 ± 28 µm) and in mice the diameter of anterior cerebral arteries (185 ± 15–222 ± 12 µm) significantly increased in the G-CSF groups compared to controls. Stroke volume in mice (10 ± 2%) was diminished following CCAO (7 ± 4%) and G-CSF treatment (4 ± 2%). G-CSF significantly increased monocyte migration in vitro and perivascular monocyte numbers in vivo. Conclusion: G-CSF augments cerebral collateral artery growth, increases CVRC and protects from experimentally induced ischemic stroke. When comparing three different dosing regimens, a relatively low dosage of G-CSF was most effective, indicating that the common side effects of this cytokine might be significantly reduced or possibly even avoided in this indication.
Cell Adhesion and Glistening Formation in Hybrid Copolymer Intraocular Lenses
Authors: Fujita Satoshi , Tanaka Takao , Miyata Akira , Hirose Maiko , Usui Masahiko
Published: April 2012

The purpose of this study is to investigate the cell adhesion and glistening formation properties of various foldable intraocular lenses (IOLs) in vitro. Three conventional hydrophobic methacrylate acrylic (MA) IOLs, a hydrophilic hydroxyethyl methacrylate (HEMA) IOL and a hybrid MA/HEMA copolymer IOL were investigated for immunologically activated cell adhesion and for formation of glistenings resulting from cavitation, by analysis of digital images using NIH Image J PC software. The MA IOLs exhibited a low level of adhering cells but a high level of glistening formation, the HEMA IOL exhibited the reverse tendency, and the MA/HEMA IOL exhibited a low level of both, thus indicating that hybrid MA/HEMA IOLs are less susceptible than HEMA IOLs to cell adhesion and less susceptible than MA IOLs to glistening formation.
A Population-Based Prospective 24-Month Study of Stroke: Incidence and 30-Day Case-Fatality Rates of First-Ever Strokes in Croatia
Authors: Pikija Slaven , Cvetko Danijel , Malojčić Branko , Trkanjec Zlatko , Pavliček Ivan , Lukić Anita , Kopjar Andrina , Hajduk Martina , Andrović Alen , Bilić-Genter Melita , Trkulja Vladimir
Published: April 2012

Background: In Central/Eastern European countries, cerebrovascular diseases are among the leading causes of mortality. We aimed to determine the incidence of first-ever stroke (FES) in the north-western part of Croatia. Methods: A population-based prospective incidence study was conducted between July 1, 2007, and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence rates by stroke type and gender were calculated. Results: A total of 1,487 events were recorded, 1,017 of which were FESs. European age-adjusted incidence rates (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) = 0.65 (95% CI 0.57–0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56–0.76); intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30–0.63); subarachnoid hemorrhage 7.2 (w/m RR = 1.18, 0.55–2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54–1.14). Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9 (w/m RR = 0.77, 0.59–0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22, 0.13–0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37–0.77) and ‘other or uncertain causes’ 70.6 (w/m RR = 0.77, 0.62–0.97). Thirty-day case-fatality rate was 23.5% overall and 17.1% for ischemic stroke. Conclusions: The incidence of FES and 30-day mortality of patients with ischemic strokes in the studied population is higher than in Western European countries.