bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and Clinical Validity of a New Questionnaire for Mikulicz's Disease
Authors: Yamamoto Motohisa , Takahashi Hiroki , Ishigami Keisuke , Yajima Hidetaka , Shimizu Yui , Tabeya Tetsuya , Matsui Mikiko , Suzuki Chisako , Naishiro Yasuyoshi , Yamamoto Hiroyuki , Imai Kohzoh , Shinomura Yasuhisa
Published: May 2012

Objectives. The characteristic features of Mikulicz’s disease (MD) are diffuse enlargement of the lacrimal and submandibular glands, elevated levels of serum immunoglobulin (Ig)G4, and abundant infiltration of IgG4-positive plasmacytes into both glands. No disease index is available to properly evaluate MD, so we developed a functional assessment of MD, the Mikulicz’s disease activity questionnaire (MAQ), and evaluated its clinical efficacy.Methods. We selected 18 patients who were either being treated for MD or who had presented with recurrence. The patients completed a self-assessment and were scored according to the MAQ sheet during each visit between December 2009 and August 2011. Assessment items were in regard to increases or decreases in lacrimal and salivary gland enlargement and severity of sicca symptoms.Results. On the first visits, MAQ scores were high, but scores decreased rapidly as treatment progressed. When doses of glucocorticoid were reduced, some patients showed increased scores. Dry-symptom scores increased initially. MAQ scores for patients with recurrent MD gradually increased over several months before relapse. However, some patients displayed no elevation in MAQ scores due to relapses at other sites.Conclusion. MAQ score can be used to quantify flares and treatment response and is useful for functional assessment of MD.
The Protective Effect of Apamin on LPS/Fat-Induced Atherosclerotic Mice
Authors: Kim Soo-Jung , Park Ji-Hyun , Kim Kyung-Hyun , Lee Woo-Ram , Pak Sok Cheon , Han Sang-Mi , Park Kwan-Kyu
Published: May 2012

Apamin, a peptide component of bee venom (BV), has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip) injections of lipopolysaccharide (LPS, 2 mg/kg) to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg) was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF)-α, vascular cell adhesion molecule (VCAM)-1, and intracellular cell adhesion molecule (ICAM)-1, as well as the nuclear factor kappa B (NF-κB) signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca2+levels, and TNF-αin the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-β1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.
Influenza Vaccine Coverage among Pregnant Women in a Public Hospital System during the 2009-2010 Pandemic Influenza Season
Authors: Coonrod Dean V. , Jimenez Blanca-Flor , Sturgeon Amber N. , Drachman David
Published: May 2012

The purpose of this study was to compare influenza vaccination rates of pregnant women in a public safety-net health system to national coverage rates during the 2009-2010 pandemic influenza season. A chart review of a random sample of deliveries was undertaken to determine rates of coverage and predictors of vaccine coverage of women who obtained prenatal care and delivered in our health system. Rates were calculated from deliveries from when the vaccine was first available through April 30, 2010. Coverage rates were 54% for the seasonal influenza vaccine and 51% for the H1N1 vaccine. Race/ethnicity, insurance status and language spoken did not predict the receipt of either vaccine. When we included only births which occurred through March 12, 2010, as was done in a large population-based study, the rates were 61% and 59%, respectively. Our rates are about 10% higher than the rates reported in that study. Our comprehensive strategy for promoting vaccine coverage achieved higher vaccination rates in a safety-net health system, which serves groups historically less likely to be vaccinated, than those reported for the pregnant population at large.
In VitroCytotoxic Potential of Essential Oils ofEucalyptus benthamiiand Its Related Terpenes on Tumor Cell Lines
Authors: Döll-Boscardin Patrícia Mathias , Sartoratto Adilson , Sales Maia Beatriz Helena Lameiro de Noronha , Padilha de Paula Josiane , Nakashima Tomoe , Farago Paulo Vitor , Kanunfre Carla Cristine
Published: May 2012

EucalyptusL. is traditionally used for many medicinal purposes. In particular, someEucalyptusspecies have currently shown cytotoxic properties. Local Brazilian communities have used leaves ofE. benthamiias a herbal remedy for various diseases, including cancer. Considering the lack of available data for supporting this cytotoxic effect, the goal of this paper was to study thein vitrocytotoxic potential of the essential oils from young and adult leaves ofE. benthamiiand some related terpenes (α-pinene, terpinen-4-ol, andγ-terpinene) on Jurkat, J774A.1 and HeLa cells lines. Regarding the cytotoxic activity based on MTT assay, the essential oils showed improved results thanα-pinene andγ-terpinene, particularly for Jurkat and HeLa cell lines. Terpinen-4-ol revealed a cytotoxic effect against Jurkat cells similar to that observed for volatile oils. The results of LDH activity indicated that cytotoxic activity of samples against Jurkat cells probably involved cell death by apoptosis. The decrease of cell DNA content was demonstrated due to inhibition of Jurkat cells proliferation by samples as a result of cytotoxicity. In general, the essential oils from young and adult leaves ofE. benthamiipresented cytotoxicity against the investigated tumor cell lines which confirms their antitumor potential.
Fatty Acid Accumulation and Resulting PPARαActivation in Fibroblasts due to Trifunctional Protein Deficiency
Authors: Wakabayashi Masato , Kamijo Yuji , Nakajima Takero , Tanaka Naoki , Sugiyama Eiko , Yangyang Tian , Kimura Takefumi , Aoyama Toshifumi
Published: May 2012

To examine fatty acid accumulation and its toxic effects in cells, we analyzed skin fibroblasts from six patients with mitochondrial trifunctional protein deficiency, who had abnormalities in the second through fourth reactions in fatty acidβ-oxidation system. We found free fatty acid accumulation, enhanced three acyl-CoA dehydrogenases, catalyzing the first reaction in theβ-oxidation system and being assumed to have normal activities in these patients, and PPARαactivation that was confirmed in the experiments using MK886, a PPARαspecific antagonist and fenofibrate, a PPARαspecific agonist. These novel findings suggest that the fatty acid accumulation and the resulting PPARαactivation are major causes of the increase in theβ-oxidation ability as probable compensation for fatty acid metabolism in the patients’ fibroblasts, and that enhanced cell proliferation and increased oxidative stress due to the PPARαactivation relate to the development of specific clinical features such as hypertrophic cardiomyopathy, slight hepatomegaly, and skeletal myopathy. Additionally, significant suppression of the PPARαactivation by means of MK886 treatment is assumed to provide a new method of treating this deficiency.
The Deleterious Influence of Tenofovir-Based Therapies on the Progression of Atherosclerosis in HIV-Infected Patients
Authors: Aragonès Gerard , Pardo-Reche Pedro , Fernández-Sender Laura , Rull Anna , Beltrán-Debón Raúl , Rodríguez-Gallego Esther , Camps Jordi , Joven Jorge , Alonso-Villaverde Carlos
Published: May 2012

We investigated the potential differential effects of antiretroviral therapies on unbalanced chemokine homeostasis and on the progression of atherosclerosis in HIV-infected patients. A two-year prospective study was performed in 67 consecutive HIV-infected patients initiating antiretroviral therapy with abacavir/lamivudine or tenofovir/emtricitabine. Circulating levels of inflammatory biomarkers, progression of subclinical atherosclerosis and expression levels of selected chemokines genes in circulating leukocytes were assessed. Control subjects showed significantly lower plasma concentrations of CRP, tPA, IL-6, and MCP-1 than HIV-infected patients at a baseline. After two years of followup, the observed decreases in plasma inflammatory biomarker levels were only significant for MCP-1, tPA, and IL-6. The decrease in plasma MCP-1 concentration was associated with the progression of atherosclerosis, and this effect was negligible only in patients receiving TDF-based therapy. Multivariate analysis confirmed that treatment with TDF was positively and significantly associated with a higher likelihood of subclinical atherosclerosis progression. However, the expression levels of selected genes in blood cells only showed associations with the viral load and total and HDL-cholesterol levels. Current antiretroviral treatments may partially attenuate the influence of HIV infection on certain inflammatory pathways, though patients receiving TDF therapy must be carefully monitored with respect to the presence and/or progression of atherosclerosis.
Drug Discovery Models and Toxicity Testing Using Embryonic and Induced Pluripotent Stem-Cell-Derived Cardiac and Neuronal Cells
Authors: Deshmukh Rahul S. , Kovács Krisztián A , Dinnyés András
Published: May 2012

Development of induced pluripotent stem cells (iPSCs) using forced expression of specific sets of transcription factors has changed the field of stem cell research extensively. Two important limitations for research application of embryonic stem cells (ESCs), namely, ethical and immunological issues, can be circumvented using iPSCs. Since the development of first iPSCs, tremendous effort has been directed to the development of methods to increase the efficiency of the process and to reduce the extent of genomic modifications associated with the reprogramming procedure. The established lineage-specific differentiation protocols developed for ESCs are being applied to iPSCs, as they have great potential in regenerative medicine for cell therapy, disease modeling either for drug development or for fundamental science, and, last but not least, toxicity testing. This paper reviews efforts aimed at practical development of iPSC differentiation to neural/cardiac lineages and further the use of these iPSCs-derived cells for drug development and toxicity testing.
Existence of Subharmonic Periodic Solutions to a Class ofSecond‐Order Non‐Autonomous Neutral Functional Differential Equations
Authors: Shu Xiao-Bao , Lai Yongzeng , Xu Fei
Published: May 2012

By introducing subdifferentiability of lower semicontinuous
convex function φ(x(t), x(t − τ)) and its conjugate function, as well
as critical point theory and operator equation theory, we obtain the existence of
multiple subharmonic periodic solutions to the following second‐order nonlinear
nonautonomous neutral nonlinear functional differential equation x″(t) + x″(t − 2τ) + f(t, x(t), x(t − τ), x(t − 2τ)) = 0, x(0) = 0.
Long‐Time Behaviour of Solutions for Autonomous Evolution Hemivariational Inequality with Multidimensional “Reaction‐Displacement” Law
Authors: Kasyanov Pavlo O. , Toscano Luisa , Zadoianchuk Nina V.
Published: May 2012

We consider autonomous evolution inclusions and hemivariational inequalities with nonsmooth dependence between determinative parameters of a problem. The dynamics of all weak solutions defined on the positive semiaxis of time is studied. We prove the existence of trajectory and global attractors and investigate their structure. New properties of complete trajectories are justified. We study classes of mathematical models for geophysical processes and fields containing the multidimensional “reaction‐displacement” law as one of possible application. The pointwise behavior of such problem solutions on attractor is described.
Simulating the Effects of Structural Parameters on the Hydraulic Performances of Venturi Tube
Authors: Sun Yanqi , Niu Wenquan
Published: May 2012

The effects of Venturi structural parameters on its hydraulic performance were studied, which provided theoretical basis for the design of Venturi injector. With an inlet diameter of 50 mm, based on the method of computational fluid dynamics (CFD), the effects of the structural parameters (such as throat taper, throat contraction ratio, and throat length) on their hydraulic performance (such as outlet faceted average velocity, minimum pressure, and critical pressure) were studied under different inlet pressures and pressure differences between inlet and outlet. A power function relationship existed between the mean velocity in outlet section and pressure difference, with an approximate flow stance index of 0.53. Minimum pressure occurred in the throat inlet wall and there was a linear relationship between the minimum pressure and the pressure difference at the inlet and outlet. The throat contraction ratio was the main factor on the effect of Venturi injector performance, which was positively correlated with outlet velocity, negatively to critical pressure, the minimal in-tube pressure, coefficient of local head loss, and fertilizer absorption ratio. For designing Venturi injector, contraction ratio should be reasonably selected according to the coefficient of local head loss and fertilizer absorption ratio.
Morphometric Analysis of Cranial Shape in Fossil and Recent Euprimates
Authors: Bennett C. Verity , Goswami Anjali
Published: May 2012

Quantitative analysis of morphology allows for identification of subtle evolutionary patterns or convergences in anatomy that can aid ecological reconstructions of extinct taxa. This study explores diversity and convergence in cranial morphology across living and fossil primates using geometric morphometrics. 33 3D landmarks were gathered from 34 genera of euprimates (382 specimens), including the Eocene adapiformsAdapisandLeptadapisand Quaternary lemursArchaeolemur,Palaeopropithecus, andMegaladapis. Landmark data was treated with Procrustes superimposition to remove all nonshape differences and then subjected to principal components analysis and linear discriminant function analysis. Haplorhines and strepsirrhines were well separated in morphospace along the major components of variation, largely reflecting differences in relative skull length and width and facial depth. Most adapiforms fell within or close to strepsirrhine space, while Quaternary lemurs deviated from extant strepsirrhines, either exploring new regions of morphospace or converging on haplorhines. Fossil taxa significantly increased the area of morphospace occupied by strepsirrhines. However, recent haplorhines showed significantly greater cranial disparity than strepsirrhines, even with the inclusion of the unusual Quaternary lemurs, demonstrating that differences in primate cranial disparity are likely real and not simply an artefact of recent megafaunal extinctions.
The Neglected Significance of “Antioxidative Stress”
Authors: Poljsak B. , Milisav I.
Published: May 2012

Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen species (ROS) in favor of the prooxidant balance, leading to potential oxidative damage. ROSs were considered traditionally to be only a toxic byproduct of aerobic metabolism. However, recently, it has become apparent that ROS might control many different physiological processes such as induction of stress response, pathogen defense, and systemic signaling. Thus, the imbalance of the increased antioxidant potential, the so-called antioxidative stress, should be as dangerous as well. Here, we synthesize increasing evidence on “antioxidative stress-induced” beneficial versus harmful roles on health, disease, and aging processes. Oxidative stress is not necessarily an un-wanted situation, since its consequences may be beneficial for many physiological reactions in cells. On the other hand, there are potentially harmful effects of “antioxidative stress,” especially in the cases of overconsumption of synthetic antioxidants. Antioxidants can neutralize ROS and decrease oxidative stress; however, this is not always beneficial in regard to disease formation or progression (of, e.g., cancer) or for delaying aging.
Voltammetric Study of the Copper Pentacyanonitrosylferrate Adsorbed on the Silica Modified with a Poly(propylene)imine Hexadecylamine Dendrimer for Determination of Nitrite
Authors: do Carmo D. R. , Gabriel S. , Silvestrini D. R. , Bicalho U. O. , Cumba L. R.
Published: May 2012

Poly(propylene)imine hexadecylamine dendrimer (DAB-Am-16) was anchored on the surface of 3-chloropropylsilyl silica gel and subsequently interacted with copper nitroprusside. The composite was characterized by infrared (FTIR), energy dispersive X-ray (EDX), and cyclic voltammetry. The above techniques confirmed the successful anchoring of the dendrimer on the silica gel modified surface and its interaction with copper nitroprusside. The cyclic voltammogram of CuNPSD was found to exhibit two redox couples with (Eθ′)1= 0.30 V and (Eθ′)2= 0.78 V versus Ag/AgCl ( mol L−1;  mV s−1) attributed to the redox processes and , respectively. The CuNPSD-modified graphite paste electrode was found to show a linear response of to  mol L−1for nitrite determination with a detection limit (DL) of  mol L−1and an amperometric sensitivity of 25.0 mA/mol L−1. The CuNPSD-modified graphite paste electrode was found to show a good electrochemical stability and an excellent response to the electrocatalytic oxidation of sodium nitrite.
Increased Extravascular Lung Water Reduces the Efficacy of Alveolar Recruitment Maneuver in Acute Respiratory Distress Syndrome
Authors: Smetkin Alexey A. , Kuzkov Vsevolod V. , Suborov Eugeny V. , Bjertnaes Lars J. , Kirov Mikhail Y.
Published: May 2012

Introduction. In acute respiratory distress syndrome (ARDS) the recruitment maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to improve arterial oxygenation. The goal of our paper was to evaluate the response to RM, as assessed by measurements of extravascular lung water index (EVLWI) in ARDS patients.Materials and Methods. Seventeen adult ARDS patients were enrolled into a prospective study. Patients received protective ventilation. The RM was performed by applying a continuous positive airway pressure of 40 cm H2O for 40 sec. The efficacy of the RM was assessed 5 min later. Patients were identified as responders if PaO2/FiO2increased by >20% above the baseline. EVLWI was assessed by transpulmonary thermodilution before the RM, and patients were divided into groups of low EVLWI (<10 mL/kg) and high EVLWI (≥10 mL/kg).Results. EVLWI was increased in 12 patients. Following RM, PaO2/FiO2increased by 33 (4–65) % in the patients with low EVLWI, whereas those in the high EVLWI group experienced a change by only −1((−13)–(+5)) % ().Conclusion. In ARDS, the response to a recruitment maneuver might be related to the severity of pulmonary edema. In patients with incresed EVLWI, the recruitment maneuver is less effective.
Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of Pulmonary Hypertension
Authors: Griffith Christopher C. , Raval Jay S. , Nichols Larry
Published: May 2012

Intravenous injection of illegal drugs or medications meant for oral administration can cause granulomatous disease of the lung. This intravascular talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of histologically confirmed intravascular talcosis were reviewed with specific attention given to the clinical histories in these patients. Five autopsy cases were included in this series with detailed investigation in the anatomic features associated with intravascular talcosis and pulmonary hypertension. All nine patients showed perivascular and/or intravascular deposition of polarizable foreign material in their lungs. Intravascular talcosis as a result of previous intravenous drug use was not clinically suspected in any patient despite clinically diagnosed pulmonary hypertension in five. All patients showed dilatation of the right and left heart, but none had dilatation of the aortic valve. Congestive heart failure with hepatosplenomegaly was also common. We conclude that intravascular talcosis is an underdiagnosed cause of pulmonary hypertension in patients with known history of intravenous drug use.
Dynamical Analysis in a Delayed Predator‐Prey Model with Two Delays
Authors: Xu Changjin , Li Peiluan
Published: May 2012

A class of Beddington‐DeAngelis functional response predator‐prey model is considered. The conditions for the local stability and the existence of Hopf bifurcation at the positive
equilibrium of the system are derived. Some explicit formulae for determining the stability and
the direction of the Hopf bifurcation periodic solutions bifurcating from Hopf bifurcations are
obtained by using the normal form theory and center manifold theory. Some numerical simulations for justifying the theoretical analysis are also provided. Finally, main conclusions are given.
Integrative Taxonomy, Phylogeny, and New Species of the Weevil GenusOnyxacallesStüben (Coleoptera: Curculionidae: Cryptorhynchinae)
Authors: Stüben Peter E. , Astrin Jonas J.
Published: May 2012

A molecular phylogeny of the western Palearctic weevil genusOnyxacallesStüben, 1999 is presented, combining two mitochondrial genes (COI and 16S) in a Bayesian analysis. Based on molecular data,Onyxacalles pyrenaeusBoheman, 1844 is transferred into the genusKyklioacallesStüben 1999 (K. faustigroup) and—in an integrative taxonomy framework—the interaction between morphology and molecular analysis is illustrated. The species ofOnyxacalless. str. are assigned to three new species groups,O. henoni,O. luigionii, andO. portusvenerisgroups. The distribution of the related species in the Mediterranean area is illustrated with values of COI and 16S p-distances. Three new species are described and distinguished from their related species:Onyxacalles nuraghiStüben sp.n. from Italy (Sardinia),Onyxacalles torreStüben and Astrin sp. n. from France (Corsica) andOnyxacalles vilaeStüben sp. n. from Croatia (Velebit Mts.). A catalogue of all 20 species ofOnyxacallesis given, and a key is finally presented combined with image stacking of the habitus and aedeagus for all species.
ZnO:Al Grown by Sputtering from Two Different Target Sources: A Comparison Study
Authors: Alnajjar Abdalla A.
Published: May 2012

Al-doped ZnO thin films were deposited from two different targets. Ceramic targets were used in RF magnetron sputtering, whereas pulsed magnetron sputtering was used to grow films from powder targets. ZnO:Al films with different thicknesses were sputtered directly on soda-lime glass substrates. The film thickness was in the 0.04–2.0 μm range. The microstructure, such as the grain size and the texture, of the two differently grown ZnO:Al transparent conductive oxide films of different thickness, was studied using X-ray diffractionθ/2θscans. The optical properties, such as the transmittance and reflectance, were measured using a UV-Vis-NIR spectrometer. Further, the sheet resistance, resistivity, carrier concentration, and Hall mobility of these ZnO:Al thin films were measured as a function of film thickness. These results obtained from the two different deposition techniques were compared and contrasted.
Activated Protein C Does Not Alleviate the Course of Systemic Inflammation in the APCAP Trial
Authors: Kyhälä Lea , Mentula Panu , Kylänpää Leena , Moilanen Eeva , Puolakkainen Pauli , Pettilä Ville , Repo Heikki
Published: May 2012

The study aimed to determine the effect of the activated protein C on the course of systemic inflammation in the APCAP (activated protein C in acute pancreatitis) trial where we randomized 32 patients with severe acute pancreatitis to receive either recombinant activated protein C (drotrecogin alfa activated) (n=16) or placebo (n=16) for 96 hours. In the present study, we present the time course of the patients’ plasma or serum levels of soluble markers (IL-8, IL-6, IL-10, IL-1ra, sE-selectin, PCT) and monocyte and neutrophil cell surface (CD11b, CD14, CD62L, HLA-DR) markers of systemic inflammatory response during the first 14 days after the randomization. The results of the intervention and placebo groups were comparable showing that recombinant APC treatment did not alter the course of systemic inflammation in severe acute pancreatitis. Our finding is in accordance with the clinical findings in the APCAP trial indicating that the intervention did not affect evolution of multiple organ dysfunctions.
Cardiovascular Risk in Patients with Psoriatic Arthritis
Authors: Zhu Tracy Y. , Li Edmund K. , Tam Lai-Shan
Published: May 2012

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. In addition to skin and joint involvement, there is increasing evidence suggesting that patients with PsA also have an increase in risk of clinical and subclinical cardiovascular diseases, mostly due to accelerating atherosclerosis. Both conventional and nonconventional cardiovascular risk factors contribute to the increased cardiovascular risk in PsA. Chronic inflammation plays a pivotal role in the pathogenesis of atherosclerosis in PsA, acting independently and/or synergistically with the conventional risk factors. In this paper, we discuss the current literature indicating that patients with PsA are at risk of cardiovascular diseases.
On the q‐Genocchi Numbers and Polynomials with Weight α and Weak Weight β
Authors: Kang J. Y. , Lee H. Y. , Jung N. S.
Published: May 2012

We construct a new type of q‐Genocchi numbers and polynomials with weight α and weak weight , respectively. Some interesting results and relationships are obtained.
Acute Pancreatitis after Kidney Transplantation
Authors: Tabakovic Mithat , Salkic Nermin N. , Bosnjic Jasmina , Alibegovic Ervin
Published: May 2012

Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient.
Synergistic Antimycobacterial Actions ofKnowltonia vesicatoria(L.f) Sims
Authors: Labuschagné Antoinette , Hussein Ahmed A. , Rodríguez Benjamín , Lall Namrita
Published: May 2012

Euclea natalensisA.DC.,Knowltonia vesicatoria(L.f) Sims, andPelargonium sidoidesDC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract ofK. vesicatoriawas subjected to fractionation to identify the active compounds. The activity of theKnowltoniaextract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL againstMycobacterium smegmatisand an MIC of 50.00 μg/mL againstM. tuberculosis. TheK. vesicatoriaextract was tested against two different drug-resistant strains ofM. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination ofK. vesicatoriawith INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated fromK. vesicatoriaas the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitiveM. tuberculosiswith an MIC of 50.00 μg/mL.
A Fuzzy Dropper for Proportional Loss Rate Differentiation under Wireless Network with a Multi‐State Channel
Authors: Szu Yu-Chin
Published: May 2012

The proportional loss rate differentiation (PLD) model was proposed to provide controllable and predictable loss rate for different classes of wired network connections. However, these algorithms cannot be directly applied to wireless networks, because of the location‐dependent and time‐varying wireless channel capacity. This paper proposes a novel packet dropper for fuzzy controlling of the proportional loss rate differentiation in a wireless network with multistate channel. The proposed dropper, fuzzy proportional loss rate dropper (FPLR), prefers to drop the small packets destined to a poor condition channel to improve the network performance. The loss rate debts of the poor channel will be compensated later to keep PLD. From simulation results, FPLR does achieve accurate loss rate proportion, lower queuing delay and loss rate, and higher throughput, compared with other methods in the wireless environment.
Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets
Authors: Lee Ye-Ming , Hsieh Kuo-Hsien , Lu Wan-Jung , Chou Hsiu-Chu , Chou Duen-Suey , Lien Li-Ming , Sheu Joen-Rong , Lin Kuan-Hung
Published: May 2012

Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulusL.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]imobilization, thromboxane A2formation, hydroxyl radical (OH●) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A2formation, thereby leading to inhibition of [Ca2+]iand finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.
Application of Generalized Space-Time Autoregressive Model on GDP Data in West European Countries
Authors: Nurhayati Nunung , Pasaribu Udjianna S. , Neswan Oki
Published: May 2012

This paper provides an application of generalized space-time autoregressive (GSTAR) model on GDP data in West European countries. Preliminary model is identified by space-time ACF and space-time PACF of the sample, and model parameters are estimated using the least square method. The forecast performance is evaluated using the mean of squared forecast errors (MSFEs) based on the last ten actual data. It is found that the preliminary model is GSTAR(2;1,1). As a comparison, the estimation and the forecast performance are also applied to the GSTAR(1;1) model which has fewer parameter. The results showed that the ASFE of GSTAR(2;1,1) is smaller than that of the order (1;1). However, thet-test value shows that the performance is significantly indifferent. Thus, due to the parsimony principle, the GSTAR(1;1) model might be considered as a forecasting model.
From Genetics to Genomics of Epilepsy
Authors: Garofalo Silvio , Cornacchione Marisa , Di Costanzo Alfonso
Published: May 2012

The introduction of DNA microarrays and DNA sequencing technologies in medical genetics and diagnostics has been a challenge that has significantly transformed medical practice and patient management. Because of the great advancements in molecular genetics and the development of simple laboratory technology to identify the mutations in the causative genes, also the diagnostic approach to epilepsy has significantly changed. However, the clinical use of molecular cytogenetics and high-throughput DNA sequencing technologies, which are able to test an entire genome for genetic variants that are associated with the disease, is preparing a further revolution in the near future. Molecular Karyotype and Next-Generation Sequencing have the potential to identify causative genes or loci also in sporadic or non-familial epilepsy cases and may well represent the transition from a genetic to a genomic approach to epilepsy.
Association of Self-Reported Weight Change and Quality of Life, and Exercise and Weight Management Behaviors Among Adults with Type 2 Diabetes Mellitus: The SHIELD Study
Authors: Grandy Susan , Fox Kathleen M. , Bazata Debbra D.
Published: May 2012

Purpose. This study examined the association between self-reported weight change and quality of life, and exercise and weight management behaviors among individuals with type 2 diabetes mellitus (T2DM).Methods. In the US SHIELD study, respondents reported whether they had lost or gained weight compared with 1 year earlier and completed the SHIELD-WQ-9 quality of life questionnaire as well as provided information on their exercise and weight management behaviors in the past 12 months.Results. Sixteen percent of the respondents reported gaining weight (n=460), and 30% reported losing weight (n=895). More respondents who reported losing weight exercised regularly, limited calorie and fat intake, and increased fiber, fruit, and vegetable intake compared with respondents who reported gaining weight (P<0.01). For all nine aspects of daily life, a significantly greater proportion of respondents who reported losing weight reported improved well-being (12%–44%) compared with respondents who reported gaining weight (P<0.0001).Conclusions. Self-reported weight loss was associated with improved well-being, better exercise, and weight management behaviors among individuals with T2DM.
Effect of Colic Vein Ligature in Rats with Loperamide-Induced Constipation
Authors: Neri Flavia , Cavallari Giuseppe , Tsivian Matvey , Bianchi Elisa , Aldini Rita , Cevenini Monica , Guidetti Elena , Piras Gian Luca , Pariali Milena , Nardo Bruno
Published: May 2012

Introduction. Medical treatment in chronic constipation is not always successful. Surgery is indicated in unresponsive selected severe cases. This study presents the distal venous colic ligation in rat as a novel surgical approach.Materials and Methods. 16 rats (study group) were evaluated in 3 phases of 6 days each: A (normal conditions), B (loperamide-induced constipation), and C (colic vein legation) and compared with rats treated in phase C with PEG 4,000 (control group). Blood biochemical and physiological parameters, daily fecal water content (FWC), and histological analysis were performed in all study phases.Results. No biochemical and physiological parameters changes were observed. FWC decreased in phase B and increased in phase C in both groups with a grow up to 2.3-fold in study group compared to control (P<0.0001). Moreover, in study group, a high number of colonic goblet cells were detected (phase C versus phase B:P<0.001) while no differences were registered in control.Conclusion. By ligature of the colic vein in constipated rats, an increase in FWC and goblet cells higher than in PEG treated rats was detected. The described surgical procedure appeared effective, simple, and safe; further studies in animal models, however, are necessary to assess its clinical applicability.
A Multiswarm Optimizer for Distributed Decision Making in Virtual Enterprise Risk Management
Authors: Shao Yichuan , Yao Xingjia , Tian Liwei , Chen Hanning
Published: May 2012

We develop an optimization model for risk management in a virtual enterprise environment based on a novel multiswarm particle swarm optimizer called PS2O. The main idea of PS2O is to extend the single population PSO to the interacting multiswarms model by constructing hierarchical interaction topology and enhanced dynamical update equations. With the hierarchical interaction topology, a suitable diversity in the whole population can be maintained. At the same time, the enhanced dynamical update rule significantly speeds up the multiswarm to converge to the global optimum. With five mathematical benchmark functions, PS2O is proved to have considerable potential for solving complex optimization problems. PS2O is then applied to risk management in a virtual enterprise environment. Simulation results demonstrate that the PS2O algorithm is more feasible and efficient than the PSO algorithm in solving this real‐world problem.
Existence of Periodic Solutions for a Class of Asymptotically p‐Linear Discrete Systems Involving p‐Laplacian
Authors: Chen Kai , Zhang Qiongfen
Published: May 2012

By applying Mountain Pass Theorem in critical point theory,
two existence results are obtained for the following asymptotically p‐linear p‐Laplacian discrete system Δ(|Δu(t−1)|p−2Δu(t − 1)) + ∇[−K(t, u(t)) + W(t, u(t))] = 0. The results obtained generalize some known works.
Total Joint Replacement in the Past Does Not Relate to a Deteriorated Functional Level and Health Status in the Oldest Old
Authors: Verra Wiebe Chr. , de Craen Anton J. M. , Jaspars Coen C. M. M. , Gussekloo Jacobijn , Blauw Gerard Jan , Westendorp Rudi G. J. , Maier Andrea B. , Nelissen Rob G. H. H.
Published: May 2012

Total hip or knee replacement is effective in improving joint function, quality of life, and pain reduction. The oldest old population with joint replacements (TJR) is underrepresented in current literature. We compared health-related and functional characteristics of oldest olds with and without TJR. Participants (aged 85 years) were divided into a group with and without TJR. Comorbidity, physical and joint functioning, daily living activities, quality of life, and mortality were recorded. Thirty-eight of 599 participants (6.3%) received a TJR in the past. Participants with a TJR had slightly less comorbidities, walked slower (P=0.006), and complained more about hip-pain (P=0.007). Mortality of those with a TJR was lower during the first 8-year followup (P=0.04). All other characteristics were comparable between groups. We conclude that subjects with a TJR performed equally well, besides showing a lower gait speed and a higher frequency of hip-pain. Except for the lower gaitspeed, having a TJR is not associated with poorer health.
Nutrition in Severe Dementia
Authors: Pivi Glaucia Akiko Kamikado , Bertolucci Paulo Henrique Ferreira , Schultz Rodrigo Rizek
Published: May 2012

An increasing proportion of older adults with Alzheimer's disease or other dementias are now surviving to more advanced stages of the illness. Advanced dementia is associated with feeding problems, including difficulty in swallowing and respiratory diseases. Patients become incompetent to make decisions. As a result, complex situations may arise in which physicians and families decide whether artificial nutrition and hydration (ANH) is likely to be beneficial for the patient. The objective of this paper is to present methods for evaluating the nutritional status of patients with severe dementia as well as measures for the treatment of nutritional disorders, the use of vitamin and mineral supplementation, and indications for ANH and pharmacological therapy.
Fibroblast-Derived Dermal Matrix Drives Development of Aggressive Cutaneous Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa
Authors: Ng Yi-Zhen , Pourreyron Celine , Salas-Alanis Julio C. , Dayal Jasbani H.S. , Cepeda-Valdes Rodrigo , Yan Wenfei , Wright Sheila , Chen Mei , Fine Jo-David , Hogg Fiona J. , McGrath John A. , Murrell Dedee F. , Leigh Irene M. , Lane E. Birgit , South Andrew P.
Published: May 2012

Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. Although gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and nontumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall, our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts. Cancer Res; 72(14); 3522–34. ©2012 AACR.
Cyclin E2 Overexpression Is Associated with Endocrine Resistance but not Insensitivity to CDK2 Inhibition in Human Breast Cancer Cells
Authors: Caldon C. Elizabeth , Sergio C. Marcelo , Kang Jian , Muthukaruppan Anita , Boersma Marijke N. , Stone Andrew , Barraclough Jane , Lee Christine S. , Black Michael A. , Miller Lance D. , Gee Julia M. , Nicholson Rob I. , Sutherland Robert L. , Print Cristin G. , Musgrove Elizabeth A.
Published: May 2012

Cyclin E2, but not cyclin E1, is included in several gene signatures that predict disease progression in either tamoxifen-resistant or metastatic breast cancer. We therefore examined the role of cyclin E2 in antiestrogen resistance in vitro and its potential for therapeutic targeting through cyclin-dependent kinase (CDK) inhibition. High expression of CCNE2, but not CCNE1, was characteristic of the luminal B and HER2 subtypes of breast cancer and was strongly predictive of shorter distant metastasis-free survival following endocrine therapy. After antiestrogen treatment of MCF-7 breast cancer cells, cyclin E2 mRNA and protein were downregulated and cyclin E2–CDK2 activity decreased. However, this regulation was lost in tamoxifen-resistant (MCF-7 TAMR) cells, which overexpressed cyclin E2. Expression of either cyclin E1 or E2 in T-47D breast cancer cells conferred acute antiestrogen resistance, suggesting that cyclin E overexpression contributes to the antiestrogen resistance of tamoxifen-resistant cells. Ectopic expression of cyclin E1 or E2 also reduced sensitivity to CDK4, but not CDK2, inhibition. Proliferation of tamoxifen-resistant cells was inhibited by RNAi-mediated knockdown of cyclin E1, cyclin E2, or CDK2. Furthermore, CDK2 inhibition of E-cyclin overexpressing cells and tamoxifen-resistant cells restored sensitivity to tamoxifen or CDK4 inhibition. Cyclin E2 overexpression is therefore a potential mechanism of resistance to both endocrine therapy and CDK4 inhibition. CDK2 inhibitors hold promise as a component of combination therapies in endocrine-resistant disease as they effectively inhibit cyclin E1 and E2 overexpressing cells and enhance the efficacy of other therapeutics. Mol Cancer Ther; 11(7); 1488–99. ©2012 AACR.
Impact of Intrinsic Affinity on Functional Binding and Biological Activity of EGFR Antibodies
Authors: Zhou Yu , Goenaga Anne-Laure , Harms Brian D. , Zou Hao , Lou Jianlong , Conrad Fraser , Adams Gregory P. , Schoeberl Birgit , Nielsen Ulrik B. , Marks James D.
Published: May 2012

Aberrant expression and activation of EGF receptor (EGFR) has been implicated in the development and progression of many human cancers. As such, targeted therapeutic inhibition of EGFR, for example by antibodies, is a promising anticancer strategy. The overall efficacy of antibody therapies results from the complex interplay between affinity, valence, tumor penetration and retention, and signaling inhibition. To gain better insight into this relationship, we studied a panel of EGFR single-chain Fv (scFv) antibodies that recognize an identical epitope on EGFR but bind with intrinsic monovalent affinities varying by 280-fold. The scFv were converted to Fab and IgG formats, and investigated for their ability to bind EGFR, compete with EGF binding, and inhibit EGF-mediated downstream signaling and proliferation. We observed that the apparent EGFR-binding affinity for bivalent IgG plateaus at intermediate values of intrinsic affinity of the cognate Fab, leading to a biphasic curve describing the ratio of IgG to Fab affinity. Mathematical modeling of antibody–receptor binding indicated that the biphasic effect results from nonequilibrium assay limitations. This was confirmed by further observation that the potency of EGF competition for antibody binding to EGFR improved with both intrinsic affinity and antibody valence. Similarly, both higher intrinsic affinity and bivalent binding improved the potency of antibodies in blocking cellular signaling and proliferation. Overall, our work indicates that higher intrinsic affinity combined with bivalent binding can achieve avidity that leads to greater in vitro potency of antibodies, which may translate into greater therapeutic efficacy. Mol Cancer Ther; 11(7); 1467–76. ©2012 AACR.
microRNA-9 Targets Matrix Metalloproteinase 14 to Inhibit Invasion, Metastasis, and Angiogenesis of Neuroblastoma Cells
Authors: Zhang Huanyu , Qi Meng , Li Shiwang , Qi Teng , Mei Hong , Huang Kai , Zheng Liduan , Tong Qiangsong
Published: May 2012

Matrix metalloproteinase (MMP)-14 is the only membrane-anchored MMP that plays a critical role in tumor metastasis and angiogenesis. However, the mechanisms underlying MMP-14 expression in tumors still remain largely unknown. In this study, MMP-14 immunostaining was identified in 29/42 neuroblastoma tissues, which was correlated with clinicopathologic features and shorter patients' survival. In subtotal 20 neuroblastoma cases, microRNA 9 (miR-9) was downregulated and inversely correlated with MMP-14 expression. Bioinformatics analysis revealed a putative miR-9–binding site in the 3′-untranslated region (3′-UTR) of MMP-14 mRNA. Overexpression or knockdown of miR-9 responsively altered both the mRNA and protein levels of MMP-14 and its downstream gene, vascular endothelial growth factor, in cultured neuroblastoma cell lines SH-SY5Y and SK-N-SH. In an MMP-14 3′-UTR luciferase reporter system, miR-9 downregulated the luciferase activity, and these effects were abolished by a mutation in the putative miR-9–binding site. Overexpression of miR-9 suppressed the invasion, metastasis, and angiogenesis of SH-SY5Y and SK-N-SH cells in vitro and in vivo. In addition, the effects of miR-9 on MMP-14 expression, adhesion, migration, invasion, and angiogenesis were rescued by overexpression of MMP-14 in these cells. Furthermore, anti-miR-9 inhibitor or knockdown of MMP-14 respectively increased or inhibited the migration, invasion, and angiogenesis of neuroblastoma cells. These data indicate that miR-9 suppresses MMP-14 expression via the binding site in the 3′-UTR, thus inhibiting the invasion, metastasis, and angiogenesis of neuroblastoma. Mol Cancer Ther; 11(7); 1454–66. ©2012 AACR.