bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted, Monitored, and Controlled Chemotherapy: A Multimodal Nanotechnology-Based Approach against Cancer
Authors: Shakeri-Zadeh Ali , Khoei Samideh , Khoee Sepideh , Sharifi Ali Mohammad , Shiran Mohammad-Bagher
Published: August 2013

We review innovative methods for treatment of cancer tumor on the basis of nanotechnology and physics to target, monitor and control release of chemotherapeutic agents. Chemotherapy is one of the main methods of treatment for cancer and plays a vital role in clinical practice, but side effects of anticancer drugs are still critical problems. Magnetic nanoparticles can be applied as an effective drug carriers and contrast agents for magnetic resonance imaging (MRI). Since certain nanoparticles have magnetic properties, they can be trapped in tumor during blood circulation by an external magnetic field. Also, polymeric nanoparticles are great candidates to encapsulate anticancer drugs and to control the release profile of drugs in biologic media. We suggest the construction of drug-loaded polymer-coated magnetic (DPM) nanoplatform with the potential for being utilized in medical imaging as well as having controlled drug release properties. Nanoplatform distribution can be monitored by MRI and with clever combination of ultrasound physics and suggested DPM nanoplatform, it would be feasible to increase the rate of drug release (in situ) and drug uptake by cancerous cell. To optimize the level of drug uptake by cancerous cell, the selection of ultrasound frequency and intensity is essential. The development of suggested method could be a new approach against cancer tumor.
Design, Synthesis, and In Vitro Antimicrobial Evaluation of Fused Pyrano[3,2-e]tetrazolo[1,5-c]pyrimidines and Diazepines
Authors: Kanakaraju Sankari , Sagar Vijay Kumar P. , Prasanna Bethanamudi , Chandramouli G. V. P.
Published: August 2013

A series of novel pyranochromene-containing tetrazoles fused with pyrimidinethiones, pyrimidines, and diazepines 3a–f, 4a–f, and 5a–f were synthesized by condensation of the corresponding tetrazoles 2a–f with carbon disulfide, benzaldehyde, and 4-methoxy phenacyl bromide, respectively. The compound 2a–f was obtained by reaction of pyrano[3,2-c]chromenes 1a–f with sodium azide. The structures of the newly synthesized compounds 2a–f to 5a–f were established on the basis of their elemental analyses, IR, 1H NMR, 13C NMR, and mass spectral data. All of the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against two fungi. Preliminary results indicate that some of them exhibited promising activities and that they deserve more consideration as potential antimicrobials.
An Approach for Identifying Cytokines Based on a Novel Ensemble Classifier
Authors: Zou Quan , Wang Zhen , Guan Xinjun , Liu Bin , Wu Yunfeng , Lin Ziyu
Published: August 2013

Biology is meaningful and important to identify cytokines and investigate their various functions and biochemical mechanisms. However, several issues remain, including the large scale of benchmark datasets, serious imbalance of data, and discovery of new gene families. In this paper, we employ the machine learning approach based on a novel ensemble classifier to predict cytokines. We directly selected amino acids sequences as research objects. First, we pretreated the benchmark data accurately. Next, we analyzed the physicochemical properties and distribution of whole amino acids and then extracted a group of 120-dimensional (120D) valid features to represent sequences. Third, in the view of the serious imbalance in benchmark datasets, we utilized a sampling approach based on the synthetic minority oversampling technique algorithm and K-means clustering undersampling algorithm to rebuild the training set. Finally, we built a library for dynamic selection and circulating combination based on clustering (LibD3C) and employed the new training set to realize cytokine classification. Experiments showed that the geometric mean of sensitivity and specificity obtained through our approach is as high as 93.3%, which proves that our approach is effective for identifying cytokines.
Analysis of IL-1βRelease from Cryopreserved Pooled Lymphocytes in Response to Lipopolysaccharide and Lipoteichoic Acid
Authors: Nair Sreelekshmi R. , Geetha C. S. , Mohanan P. V.
Published: August 2013

Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1β, IL-6, and TNF-α. The present study was to analyze the influence of cryopreservation in IL-1βrelease, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTAin vitro. The inflammatory cytokine, IL-1βrelease, was measured by ELISA method. It was observed that the release of IL-1βincreases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation.
Integrated Validation System for the Simulation of Diverse Sensors in WSNs
Authors: Kim Hyun-Woo , Jeong Young-Sik
Published: August 2013

In wireless sensor networks (WSNs), sensors use different types of information, such as temperatures, humidity, magnetic fields, and sound; their communication distances and battery sizes and capacities may be different. Differences in communication distances and battery capacities when the same communication method is used affect the life of the entire sensor network topology. Tests for the maximum life of the sensor network topology require many sensor nodes and huge proportional costs. In addition, experiments to verify new ideas for WSNs as alternatives to existing methods also require large expenditures. Since experiments with the arrangement of actual sensors are expensive, such experiments are conducted using simulators so that solutions for protocol design and verification can be compared through software. Existing simulators are tailored to certain sensor characteristics, so that only quite limited results can be obtained through the implementation of simulated operations, simulations of sensor arrangements, and the comparison of limited information transmission routing functions provided by simulators. This paper proposes diverse sensor definable simulators (DSDs) for the performance of experiments on diverse sensors with different communication distances in WSN environments where Geography Markup Language (GML) based coordinates are utilized.
Gene-Based Antibody Strategies for Prion Diseases
Authors: Cardinale Alessio , Biocca Silvia
Published: August 2013

Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of neurodegenerative and infectious disorders characterized by the conversion of a normal cellular protein PrPCinto a pathological abnormally folded form, termed PrPSc. There are neither available therapies nor diagnostic tools for an early identification of individuals affected by these diseases. New gene-based antibody strategies are emerging as valuable therapeutic tools. Among these, intrabodies are chimeric molecules composed by recombinant antibody fragments fused to intracellular trafficking sequences, aimed at inhibiting,in vivo, the function of specific therapeutic targets. The advantage of intrabodies is that they can be selected against a precise epitope of target proteins, including protein-protein interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar assemblies). Herein, we address and discussin vitroandin vivoapplications of intrabodies in prion diseases, focussing on their therapeutic potential.
Polyphenolic Contents and Antioxidant Properties of Different Grape (V. vinifera,V. labrusca, andV. hybrid) Cultivars
Authors: Nile Shivraj Hariram , Kim S. H. , Ko Eun Young , Park Se Won
Published: August 2013

The polyphenolic contents and the antioxidant activity of the skins and pulps of different grape cultivars were estimated using HPLC and DPPH antioxidant assay, respectively. The phenolics and flavonoids identified were quercetin, kaempferol, caffeic acid, p-coumaric acid, cinnamic acid, and (−)-epicatechin. The total phenolic contents were found to be the highest in the grape skin of Flouxa (>400 mg/100 g), followed by Campbell Early and Tamnara (>300 mg/100 g), and then by Red Globe and Ruby Seedless (>250 mg/100 g), and the total phenolic content was the lowest in Italia and Delaware (<60 mg/100 g). The antioxidant activities of the grape extracts varied from 12.5% (Ruby Seedless) to 60.2% (Hongiseul) for skins, whereas the antioxidant activities of the grape extracts varied from 35.4% (Campbell Early) to 84.5% (Hongiseul) for pulps. The grape pulps have stronger antioxidant activities than those of the grape skins. Our results suggest that the phenolic and flavonoid contents in extracts of grape skins and pulps showed statistically significant correlations with the free radical scavenging activity.
Glycophenotype Evaluation in Cutaneous Tumors Using Lectins Labeled with Acridinium Ester
Authors: Lima Luiza Rayanna Amorim , Bezerra Matheus Filgueira , Almeida Sinara Mônica Vitalino , Silva Lúcia Patrícia Bezerra Gomes , Beltrão Eduardo Isidoro Carneiro , Carvalho Júnior Luiz Bezerra
Published: August 2013

Background. Tumor cells show alterations in their glycosylation patterns when compared to normal cells. Lectins can be used to evaluate these glycocode changes. Chemiluminescence assay is an effective technique for quantitative analysis of proteins, nucleic acids, and carbohydrates due to its high sensitivity, specificity, and rapid testing.Objective. To use histochemiluminescence based on lectin conjugated to acridinium ester (AE) for the investigation of glycophenotype changes in cutaneous tumors.Methods. Concanavalin A (Con A), Peanut agglutinin (PNA),Ulex europaeusagglutinin-I (UEA-I), andMaackia amurensisagglutinin (MAA) were conjugated to acridinium ester. Biopsies of cutaneous tumors and normal skin were incubated with the lectins-AE, and chemiluminescence was quantified and expressed as Relative Light Units (RLU).Results. Actinic keratosis (AK), keratoacanthoma (KA), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) showed lower expression ofα-D-glucose/mannose andα-L-fucose residues compared to normal tissue. Cutaneous tumors displayed higher expression of Gal-β(1-3)-GalNAc residues than normal tissue. AK and SCC exhibited higher expression of Neu5Ac-α(2,3)Gal residues than normal epidermis. KA and BCC showed equivalent RLU values compared to normal tissue.Conclusions. Lectin histochemiluminescence allowed quantitative assessment of the carbohydrate expression in cutaneous tissues, contributing to eliminate the subjectivity of conventional techniques used in the histopathological diagnosis.
Patient Complaint Cases in Primary Health Care: What Are the Characteristics of General Practitioners Involved?
Authors: Birkeland Søren , Christensen Rene dePont , Damsbo Niels , Kragstrup Jakob
Published: August 2013

Background.Limited knowledge exists about factors increasing the risk of general practitioners becoming involved in a complaint case or getting disciplined in connection with a complaint case.Aim.The present study aimed to identify the general practitioner and practice characteristics associated with complaint cases and discipline.Methods.Information on general practitioners involved in complaint case decisions during one year (2007) was linked to Danish National register data on all general practitioners (). Logistic regression was used for statistical analysis.Results.With regard to complaints concerning daytime services (), the professional seniority of the general practitioner was positively associated with the odds of receiving a complaint decision (OR = 1.44 per 20 years of seniority; CI 95%, 1.04–1.98). Likewise, having more consultations per day was associated with increased odds (OR = 1.29 per 10 extra consultations per day; CI 95%, 1.07–1.54). No statistically significant association could be demonstrated between being disciplined and general practitioner or practice characteristics.Conclusion.The possible relationship between professional seniority, rate of consultations, and complaint cases merits further studies to clarify the impact of professional seniority and workload on professional performance and to furthermore consider the role of factors such as job content and communication styles.
Multiple Cementoblastoma: A Rare Case Report
Authors: Iannaci G. , Luise R. , Iezzi G. , Piattelli A. , Salierno A.
Published: August 2013

Benign cementoblastoma is a rare ectomesenchymal odontogenic tumor that originates from the root of the tooth and that is characterized by the formation of cementum-like tissue. A 60-year old man was referred to us complaining of pain in his right jaw. The patient underwent TC dental scan of the mandible, which highlighted the presence of three well-circumscribed, round, unilocular neoformations of radiopaque appearance with a radiotransparent edge, one of which was in close contact with the roots of the lower right second molar. Microscopic examination of the greater sample consisted, in its central portion, of dense mineralized acellular trabeculae of basophilic tissue cement-like, devoid of vessels, adhering to the root of the tooth, while peripherally was observed a zone of vascularized osteoid surrounded, occasionally, by a thin rim of cementoblasts mixed with fibrous tissue and inflammatory elements. This lesion was diagnosed as cementoblastoma. The second lesion appeared radiologically and histologically entirely identical to cementoblastoma, but it did not show the intimate association with the root of involved tooth. After a careful review of the literature, the diagnosis of residual cementoblastoma was made. The clinicopathologic features, treatment, and prognosis of this rare tumor are here discussed for the young dental practitioner.
Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases
Authors: Properzi Francesca , Pocchiari Maurizio
Published: August 2013

Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrPC), namedPrPTSE. In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent periodPrPTSE, the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit ofPrPTSEdetection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided.
Size Effect and Material Property Effect of the Impactor on the Damage Modes of the Single‐Layer Kiewitt‐8 Reticulated Dome
Authors: Lin Li , Fan Feng , Zhi XuDong , Yin HongFeng
Published: August 2013

The dynamic response of large space structures under accidental impact has been the subject of intense research since the occurrence of the 9/11 incident. In the present paper, using the 3D ANSYS/LS‐DYNA, size effect and material property effect of the impactor on the damage modes of the single‐layer Kiewitt‐8 reticulated dome were investigated, respectively, where the impactor was the cylinder and the impact direction was vertical. Firstly, analytical results with the rigid impactor indicated that the impactor size can change the damage mode of the reticulated dome. It was found that the probability happening to the global collapse has an obvious rise with the size increase of the impactor. Furthermore, the deformable impactor was considered to figure out the difference with the rigid impactor; the comparisons indicated that the deformable impactor, which has the same mass and the same striking velocity with the rigid impactor, can contribute to the occurrence of the global collapse at a certain initial striking condition.
Synthesis, Crystal Structure, and Comparative Study of a New Organic Material 3,4‐Diaminobenzophenone Semihydrate
Authors: Ben Rhaiem Tarek , Boughzala Habib , Driss Ahmed
Published: August 2013

The new organic 3,4‐diaminobenzophenone semihydrate (34ABPH) is grown by slow evaporation method. The compound crystallizes in the monoclinic space group: C2. The unit cell dimensions are a = 28.703 (8) Å, b = 4.722 (2) Å, c = 8.7076 (10) Å, and β = 99.40 (2)° with Z = 2. The crystal structure analysis reveals that the C13H12N2O molecules chains are organized into a double ribbon in the (b,c) plane. The structural components interact by N–H⋯O and O–H⋯O hydrogen bonds, building up a two‐dimensional network. The presence of functional groups in the molecular structure is confirmed by the Fourier transform infrared (FT‐IR) spectroscopy. Thermogravimetric analysis (TGA) confirms the presence of the water molecule.
Human Immunodeficiency Virus and Pulmonary Arterial Hypertension
Authors: Mirrakhimov Aibek E. , Ali Alaa M. , Barbaryan Aram , Prueksaritanond Suartcha
Published: August 2013

Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments.
Hexavalent Chromate Reductase Activity in Cell Free Extracts ofPenicilliumsp.
Authors: Arévalo-Rangel Damaris L. , Cárdenas-González Juan F. , Martínez-Juárez Víctor M. , Acosta-Rodríguez Ismael
Published: August 2013

A chromium-resistant fungus isolated from contaminated air with industrial vapors can be used for reducing toxic Cr(VI) to Cr(III). This study analyzes in vitro reduction of hexavalent chromium using cell free extract(s) of the fungus that was characterized based on optimal temperature, pH, use of electron donors, metal ions and initial Cr(VI) concentration in the reaction mixture. This showed the highest activity at 37°C and pH 7.0; there is an increase in Cr(VI) reductase activity with addition of NADH as an electron donor, and it was highly inhibited by Hg2+, Ca2+and Mg2+, and azide, EDTA, and KCN.
Wnt1 Accelerates anEx VivoExpansion of Human Cord Blood CD34+CD38−Cells
Authors: Chotinantakul Kamonnaree , Prasajak Patcharee , Leeanansaksiri Wilairat
Published: August 2013

Cord blood hematopoietic stem cells (CB-HSCs) transplantation has been increasing gradually with facing the limitation of insufficient quantity of HSCs in each CB unit. Therefore, efficient expansion methods which can maintain stem cell characteristics are needed. In this study, umbilical CB-CD34+cells were cultured in two different cytokine cocktails: 4 factors (4F = Flt3-L, SCF, IL-6, and TPO) and 5 factors (5F = Wnt1 + 4F) in both serum and serum-free media. The data revealed that the best condition to accelerate an expansion of CD34+CD38−cells was serum-free culture condition supplemented with 5F (5F KSR). This condition yielded 24.3 ± 2.1 folds increase of CD34+CD38−cells. The expanded cells exhibited CD34+CD38−CD133+CD71lowCD33lowCD3−CD19−markers, expressednanog, oct3/4, c-myc,andsox2genes, and maintained differentiation potential into lymphoid, erythroid and myeloid lineages. The achievement of CD34+CD38−cells expansion may overcome an insufficient quantity of the cells leading to the improvement of the stem cell transplantation. Altogether, our findings highlight the role of Wnt1 and the new culture condition in stimulating hematopoietic stem/progenitor cells expansion which may offer a new therapeutic avenue for cord blood transplantation, regenerative medicine, stem cell bank applications, and other clinical applications in the future.
Plasma Gamma-Glutamyltransferase Is Strongly Determined by Acylation Stimulating Protein Levels Independent of Insulin Resistance in Patients with Acute Coronary Syndrome
Authors: Saleh Jumana , Farhan Hatem , Al-Saqri Ibtisam , Al-Riyami Bashair , Cianflone Katherine
Published: August 2013

Background.Steatosis is a manifestation of the metabolic syndrome often associated with release of liver enzymes and inflammatory adipocytokines linked to cardiovascular risk. Gamma-glutamyltransferase (GGT) is one sensitive liver marker recently identified as an independent cardiovascular risk factor. Mechanisms involved in enhanced hepatic lipogenesis causing steatosis are not yet identified and are usually linked to insulin resistance (IR). Acylation stimulating protein (ASP), a potent lipogenic factor, was recently shown to increase in patients with steatosis and was implicated in its pathogenesis.Aim.To investigate the association of plasma ASP levels with liver and metabolic risk markers in acute coronary syndrome (ACS) patients.Methods.28 patients and 30 healthy controls were recruited. Their anthropometrics, lipid profile, liver markers, insulin, and ASP levels were measured.Results.In the patients, ASP, liver, and metabolic risk markers were markedly higher than in the controls. ASP strongly predicted GGT levels (B=0.75,P<0.0001), followed by triglycerides (B=0.403,P=0.017), together determining 57.6% variation in GGT levels. Insulin and IR correlated with metabolic risk components but not with liver enzymes.Conclusion.The strong association of ASP with GGT in ACS patients suggests that ASP, independent of IR, may contribute to a vicious cycle of hepatic lipogenic stimulation and GGT release promoting atherogenesis.
Optimization and Modelling of Chemical Oxygen Demand Removal by ANAMMOX Process Using Response Surface Methodology
Authors: Jalilzadeh Ali , Nabizadeh Ramin , Mesdaghinia Alireza , Azimi Aliakbar , Nasseri Simin , Mahvi Amir Hossein , Naddafi Kazem
Published: August 2013

A systematic model for chemical oxygen demand (COD) removal using the ANAMMOX (Anaerobic AMMonium OXidation) process was provided based on an experimental design. At first, the experimental data was collected from a combined biological aerobic/anaerobic reactor. For modelling and optimization of COD removal, the main parameters were considered, such as COD loading, ammonium, pH, and temperature. From the models, the optimum conditions were determined as COD 97.5 mg/L, ammonium concentration equal to 28.75 mg‐N/L, pH 7.72, and temperature 31.3°C. Finally, the analysis of the optimum conditions, performed by the response surface method, predicted COD removal efficiency of 81.07% at the optimum condition.
Optimization of Sulfide/Sulfite Pretreatment of Lignocellulosic Biomass for Lactic Acid Production
Authors: Idrees Muhammad , Adnan Ahmad , Qureshi Fahim Ashraf
Published: August 2013

Potential of sodium sulfide and sodium sulfite, in the presence of sodium hydroxide was investigated to pretreat the corncob (CC), bagasse (BG), water hyacinth and rice husk (RH) for maximum digestibility. Response Surface Methodology was employed for the optimization of pretreatment factors such as temperature, time and concentration of Na2S and Na2SO3, which had high coefficient of determination (R2) along with low probability value (P), indicating the reliable predictability of the model. At optimized conditions, Na2S and Na2SO3remove up to 97% lignin, from WH and RH, along with removal of hemicellulose (up to 93%) during pretreatment providing maximum cellulose, while in BG and CC; 75.0% and 90.0% reduction in lignin and hemicellulose was observed. Saccharification efficiency of RH, WH, BG and CC after treatment with 1.0% Na2S at 130°C for 2.3–3.0 h was 79.40, 85.93, 87.70, and 88.43%, respectively. WH treated with Na2SO3showed higher hydrolysis yield (86.34%) as compared to Na2S while other biomass substrates showed 2.0–3.0% less yield with Na2SO3. Resulting sugars were evaluated as substrate for lactic acid production, yielding 26.48, 25.36, 31.73, and 30.31 gL−1of lactic acid with 76.0, 76.0, 86.0, and 83.0% conversion yield from CC, BG, WH, and RH hydrolyzate, respectively.
OralPanax notoginsengPreparation for Coronary Heart Disease: A Systematic Review of Randomized Controlled Trials
Authors: Shang Qinghua , Xu Hao , Liu Zhaolan , Chen Keji , Liu Jianping
Published: August 2013

This systematic review aims to evaluate current evidence for the benefit and side effect of oralPanax notoginsengpreparation for coronary heart disease (CHD). We included 17 randomized clinical trials (17 papers and 1747 participants). Comparing with no intervention on the basis of conventional therapy, oralPanax notoginsengdid not show significant effect on reducing cardiovascular events, but it could alleviate angina pectoris (including improving the symptoms of angina pectoris [RR 1.20; 95% CI 1.12 to 1.28; 7 trials,n=791], improving electrocardiogram [RR 1.35; 95% CI 1.19 to 1.53; 8 trials,n=727], decreasing the recurrence of angina pectoris [RR 0.38; 95% CI 0.16 to 0.94; 1 trials,n=60], duration of angina pectoris [RR −1.88; 95% CI −2.08 to −1.69; 2 trials,n=292], and dosage of nitroglycerin [MD −1.13; 95% CI −1.70 to −0.56; 2 trials,n=212]); oralPanax notoginsenghad no significant difference compared with isosorbide dinitrate on immediate effect for angina pectoris [RR 0.96; 95% CI 0.81 to 1.15; 1 trial,n=80]. In conclusion, oralPanax notoginsengpreparation could relieve angina pectoris related symptoms. However, the small sample size and potential bias of most trials influence the convincingness of this conclusion. More rigorous trials with high quality are needed to give high level of evidence, especially for the potential benefit of cardiovascular events.
RP-HPLC Method Development and Validation for Simultaneous Estimation of Clarithromycin and Paracetamol
Authors: Gangishetty Sadana , Verma Surajpal
Published: August 2013

The present work describes a simple, rapid, and reproducible reverse phase high performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of clarithromycin (CLA) and paracetamol (PCM). C18 column (Kromasil ODS, 5 µm, 250 × 4.6 mm) and a mobile phase containing phosphate buffer (0.05 M) along with 1-octane sulphonic acid sodium salt monohydrate (0.005 M) adjusted to pH 3.2: acetonitrile (50 : 50 v/v) mixture was used for the separation and quantification. The flow rate was 1.0 mL/min and the eluents were detected by UV detector at 205 nm. The retention times were found to be 2.21 and 3.73 mins, respectively. The developed method was validated according to ICH guidelines Q2 (R1) and found to be linear within the range of 75–175 µg/mL for both drugs. The developed method was applied successfully for assay of clarithromycin and paracetamol in their combined in-house developed dosage forms and in vitro dissolution studies.
Novel Treatment for Mantle Cell Lymphoma Including Therapy-Resistant Tumor by NF-κB and mTOR Dual-Targeting Approach
Authors: Chaturvedi Nagendra K. , Rajule Rajkumar N. , Shukla Ashima , Radhakrishnan Prakash , Todd Gordon L. , Natarajan Amarnath , Vose Julie M. , Joshi Shantaram S.
Published: August 2013

Mantle cell lymphoma (MCL) is one of the most aggressive B-cell non-Hodgkin lymphomas with a median survival of approximately five years. Currently, there is no curative therapy available for refractory MCL because of relapse from therapy-resistant tumor cells. The NF-κB and mTOR pathways are constitutively active in refractory MCL leading to increased proliferation and survival. Targeting these pathways is an ideal strategy to improve therapy for refractory MCL. Therefore, we investigated the in vitro and in vivo antilymphoma activity and associated molecular mechanism of action of a novel compound, 13-197, a quinoxaline analog that specifically perturbs IκB kinase (IKK) β, a key regulator of the NF-κB pathway. 13-197 decreased the proliferation and induced apoptosis in MCL cells including therapy-resistant cells compared with control cells. Furthermore, we observed downregulation of IκBα phosphorylation and inhibition of NF-κB nuclear translocation by 13-197 in MCL cells. In addition, NF-κB–regulated genes such as cyclin D1, Bcl-XL, and Mcl-1 were downregulated in 13-197–treated cells. In addition, 13-197 inhibited the phosphorylation of S6K and 4E-BP1, the downstream molecules of mTOR pathway that are also activated in refractory MCL. Further, 13-197 reduced the tumor burden in vivo in the kidney, liver, and lungs of therapy-resistant MCL-bearing nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice compared with vehicle-treated mice; indeed, 13-197 significantly increased the survival of MCL-transplanted mice. Together, results suggest that 13-197 as a single agent disrupts the NF-κB and mTOR pathways leading to suppression of proliferation and increased apoptosis in malignant MCL cells including reduction in tumor burden in mice. Mol Cancer Ther; 12(10); 2006–17. ©2013 AACR.
Molecular Radiotherapy Using Cleavable Radioimmunoconjugates That Target EGFR and γH2AX
Authors: Cornelissen Bart , Waller Andrew , Able Sarah , Vallis Katherine A.
Published: August 2013

Many anticancer therapies, including ionizing radiation (IR), cause cytotoxicity through generation of DNA double-strand breaks (DSB). Delivery of therapeutic radionuclides to DNA DSB sites can amplify this DNA damage, for additional therapeutic gain. Herein, we report on two radiopharmaceuticals, radiolabeled with the Auger electron emitter 111In, with dual specificity for both the intranuclear, DNA damage repair signaling protein γH2AX and the EGF receptor (EGFR). The EGFR ligand EGF was conjugated to a fluorophore- or 111In-labeled anti-γH2AX antibody, linked via a nuclear localization sequence (NLS) to ensure nuclear translocation. EGF conjugation was achieved either through a noncleavable PEG linker (PEO6) or a cleavable disulfide bond. Both conjugates selectively bound EGFR on fixed cells and γH2AX in cell extracts. Both compounds enter EGFR-expressing cells in an EGF/EGFR-dependent manner. However, only the cleavable compound was seen to associate with γH2AX foci in the nuclei of irradiated cells. Intracellular retention of the cleavable compound was prolonged in γH2AX-expressing cells. Clonogenic survival was significantly reduced when cells were exposed to IR (to induce γH2AX) plus 111In-labeled cleavable compound compared to either alone and compared to nonspecific controls. In vivo, uptake of 111In-labeled cleavable compound in MDA-MB-468 xenografts in athymic mice was 2.57 ± 0.47 percent injected dose/g (%ID/g) but increased significantly to 6.30 ± 1.47%ID/g in xenografts where γH2AX was induced by IR (P < 0.01). This uptake was dependent on EGF/EGFR and anti-γH2AX/γH2AX interactions. We conclude that tumor-specific delivery of radiolabeled antibodies directed against intranuclear epitopes is possible using cleavable antibody–peptide conjugates. Mol Cancer Ther; 12(11); 2472–82. ©2013 AACR.
Vitamin E δ-Tocotrienol Prolongs Survival in the LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) Transgenic Mouse Model of Pancreatic Cancer
Authors: Husain Kazim , Centeno Barbara A. , Chen Dung-Tsa , Hingorani Sunil R. , Sebti Said M. , Malafa Mokenge P.
Published: August 2013

Previous work has shown that vitamin E δ-tocotrienol (VEDT) prolongs survival and delays progression of pancreatic cancer in the LSL-KrasG12D/+;Pdx-1-Cre mouse model of pancreatic cancer. However, the effect of VEDT alone or in combination with gemcitabine in the more aggressive LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) mouse model is unknown. Here, we studied the effects of VEDT and the combination of VEDT and gemcitabine in the KPC mice. KPC mice were randomized into four groups: (i) vehicle [olive oil, 1.0 mL/kg per os twice a day and PBS 1.0 mL/kg intrapertoneally (i.p.) twice a week], (ii) gemcitabine (100 mg/kg i.p. twice a week), (iii) VEDT (200 mg/kg per os twice a day), and (iv) gemcitabine + VEDT. Mice received treatment until they displayed symptoms of impending death from pancreatic cancer, at which point animals were euthanized. At 16 weeks, survival was 10% in the vehicle group, 30% in the gemcitabine group, 70% in the VEDT group (P < 0.01), and 90% in the VEDT combined with gemcitabine group (P < 0.05). VEDT alone and combined with gemcitabine resulted in reversal of epithelial-to-mesenchymal transition in tumors. Biomarkers of apoptosis (plasma CK18), PARP1 cleavage, and Bax expression were more greatly induced in tumors subjected to combined treatment versus individual treatment. Combined treatment induced cell-cycle inhibitors (p27Kip1 and p21Cip1) and inhibited VEGF, vascularity (CD31), and oncogenic signaling (pAKT, pMEK, and pERK) greater than individual drugs. No significant differences in body weight gain between drug treatment and control mice were observed. These results strongly support further investigation of VEDT alone and in combination with gemcitabine for pancreatic cancer prevention and treatment. Cancer Prev Res; 6(10); 1074–83. ©2013 AACR.
Evolution of Complex Higher Brain Centers and Behaviors: Behavioral Correlates of Mushroom Body Elaboration in Insects
Authors: Farris Sarah M.
Published: August 2013

Large, complex higher brain centers have evolved many times independently within the vertebrates, but the selective pressures driving these acquisitions have been difficult to pinpoint. It is well established that sensory brain centers become larger and more structurally complex to accommodate processing of a particularly important sensory modality. When higher brain centers such as the cerebral cortex become greatly expanded in a particular lineage, it is likely to support the coordination and execution of more complex behaviors, such as those that require flexibility, learning, and social interaction, in response to selective pressures that made these new behaviors advantageous. Vertebrate studies have established a link between complex behaviors, particularly those associated with sociality, and evolutionary expansions of telencephalic higher brain centers. Enlarged higher brain centers have convergently evolved in groups such as the insects, in which multimodal integration and learning and memory centers called the mushroom bodies have become greatly elaborated in at least four independent lineages. Is it possible that similar selective pressures acting on equivalent behavioral outputs drove the evolution of large higher brain centers in all bilaterians? Sociality has greatly impacted brain evolution in vertebrates such as primates, but it has not been a major driver of higher brain center enlargement in insects. However, feeding behaviors requiring flexibility and learning are associated with large higher brain centers in both phyla. Selection for the ability to support behavioral flexibility appears to be a common thread underlying the evolution of large higher brain centers, but the precise nature of these computations and behaviors may vary.
Hospital Reputation and Perceptions of Patient Safety
Authors: Mira José Joaquín , Lorenzo Susana , Navarro Isabel
Published: August 2013

Objective: The objective of this study was to explore the theoretical relationship between the social reputation and the perceived safety of a hospital. Subjects and Methods: A random sample of 316 patients and 27 relatives of patients who were unable to respond themselves at four public hospitals in Madrid, Barcelona and Alicante were interviewed to establish a measure of reputation and perceived safety. Results: There were no different perceptions between patients and relatives regarding hospital reputation or safety perception (p > 0.05). The perception of patients or relatives of health professionals' competence (β = 0.07, 95% CI 0.01-0.12), the perception of a positive treatment output of surgical or medical treatment (β = 0.35, 95% CI 0.22-0.49) and hospital reputation (β = 0.08, 95% CI 0.02-0.14) were directly and positively associated with their perception that the hospital was a safe clinical environment in which few clinical errors are committed. Conclusions: The data suggested that the social reputation of these hospitals and the perceptions of patients or relatives of patient safety were indeed correlated. Future research should assess whether efforts to enhance hospital reputation, by improving patients' perceptions of clinical safety, may contribute to reducing the frequency of litigation cases.
Acute Myocardial Infarction Caused by Tumor-Associated Thrombotic Thrombocytopenic Purpura: Case Report
Authors: Wang Jun , Cai Xiaomin , Cheng Xunmin , Song Ping , Jiang Shisen , Gong Jianbin
Published: August 2013

Objective: To describe a case with acute myocardial infarction caused by gastric carcinoma-associated thrombotic thrombocytopenic purpura. Clinical Presentation and Intervention: A 79-year-old man was admitted with abdominal pain and pyrexia. He later developed cardiac complications and microangiopathy that indicated worsening progression. Manifold evidence confirmed the diagnosis of myocardial infarction caused by thrombotic thrombocytopenic purpura. The patient was treated mainly with plasma transfusion incorporated with steroids. Conclusion: This case should remind physicians to consider microangiopathy as a differential diagnosis in patients with unexplained cardiac symptoms or atypical presentation. Early diagnosis and treatment are helpful in decreasing the sequelae of this syndrome.
Assessment of Printed Patient-Educational Materials for Chronic Kidney Disease
Authors: Tuot Delphine S. , Davis Elizabeth , Velasquez Alexandra , Banerjee Tanushree , Powe Neil R.
Published: August 2013

Background: Awareness of chronic kidney disease (CKD) is suboptimal among patients with CKD, perhaps due to poor readability of patient education materials (PEMs). We reviewed the suitability and readability of common PEMs that focused on 5 content areas: basics of CKD, risk factors for CKD development, risk factors for CKD progression, complications of CKD and self-management strategies to improve kidney health. Methods: Three reviewers (nephrologist, primary care physician, patient) used the Suitability Assessment of Materials to rate PEMs on message content/stimulation of learning, typography, visuals and layout and determined literacy level. Mean ratings were calculated for each PEM by content area and overall (superior = 70-100; adequate = 40-69; inadequate = <40). Linear regression was used to determine the impact of literacy level on mean rating. Results: We reviewed 69 PEMs from 19 organizations, divided into 113 content area sections. Most (79%) PEM sections were ‘adequate' (mean rating, 58.3%). Inclusion of patient-centered content and opportunities for patient interaction were associated with ‘superior' ratings. Mean ratings (SD) were similar across content areas: basics of CKD, 58.9% (9.1); risk factors for CKD development, 57.0% (12.3); risk factors for CKD progression, 58.5% (12.0); CKD complications, 62.3% (15.7), and self-management strategies, 62.2% (12.3). ≤6th grade literacy level (vs. >6th grade) was associated with an 11.7 point higher mean rating. Conclusion: Most PEMs for kidney disease were adequate. Outstanding PEMs shared characteristics of patient centeredness, a low literacy level, and patient interaction. Providers should be aware of strengths and limitations of PEMs when educating their patients about CKD.
Prospective Quality Initiative to Maximize Dysphagia Screening Reduces Hospital-Acquired Pneumonia Prevalence in Patients With Stroke
Authors: Titsworth W. Lee , Abram Justine , Fullerton Amy , Hester Jeannette , Guin Peggy , Waters Michael F. , Mocco J
Published: August 2013

Background and Purpose—

Dysphagia can lead to pneumonia and subsequent death after acute stroke. However, no prospective study has demonstrated reduced pneumonia prevalence after implementation of a dysphagia screen.

Methods—

We performed a single-center prospective interrupted time series trial of a quality initiative to improve dysphagia screening. Subjects included all patients with ischemic or hemorrhagic stroke admitted to our institution over 42 months with a 31-month (n=1686) preintervention and an 11-month (n=648) postintervention period. The intervention consisted of a dysphagia protocol with a nurse-administered bedside dysphagia screen and a reflexive rapid clinical swallow evaluation by a speech pathologist.

Results—

The dysphagia initiative increased the percentage of patients with stroke screened from 39.3% to 74.2% (
P
<0.001). Furthermore, this initiative coincided with a drop in hospital-acquired pneumonia from 6.5% to 2.8% among patients with stroke (
P
<0.001). Patients admitted postinitiative had 57% lower odds of pneumonia, after controlling for multiple confounds (odds ratio=0.43; confidence interval, 0.255–0.711;
P
=0.0011). The best predictors of pneumonia were stroke type (
P
<0.0001), oral intake status (
P
<0.0001), dysphagia screening status (
P
=0.0037), and hospitalization before the beginning of the quality improvement initiative (
P
=0.0449).

Conclusions—

A quality improvement initiative using a nurse-administered bedside screen with rapid bedside swallow evaluation by a speech pathologist improves screening compliance and correlates with decreased prevalence of pneumonia among patients with stroke.
Granulocyte Colony–Stimulating Factor in Patients With Acute Ischemic Stroke
Authors: Ringelstein E. Bernd , Thijs Vincent , Norrving Bo , Chamorro Angel , Aichner Franz , Grond Martin , Saver Jeff , Laage Rico , Schneider Armin , Rathgeb Frank , Vogt Gerhard , Charissé Gabriele , Fiebach Jochen B. , Schwab Stefan , Schäbitz Wolf R. , Kollmar Rainer , Fisher Marc , Brozman Miroslav , Skoloudik David , Gruber Franz , Leal Joaquin Serena , Veltkamp Roland , Köhrmann Martin , Berrouschot Jörg ,   AXIS2 Study Organization,   Data safety monitoring board:, Egerer Gerlinde , Mikus Gerd , Limmroth Volker , Kieser Meinhard ,   Monitoring and data collection: FGK, Munich Germany.,   Image acquisition procedures and analysis: BioClinica, Lyon, Bracoud Luc ,   MRI reading group:, Fiebach Jochen B. , Hermier Marc , Bouffard Juliette ,   Study medication: Theorem, Bad Soden Germany, Weber Rüdiger
Published: August 2013

Background and Purpose—

Granulocyte colony–stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose–escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients.

Methods—

G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836;
www.clinicaltrial.gov
). Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging).

Results—

G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1.

Conclusions—

G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00927836.
Ultrastructure and distribution of Urosolenia obesa sp. nov. (Rhizosoleniaceae, Diatomeae) in reservoirs from southern Brazil
Authors: TREMARIN PRISCILA I. , FREIRE EDUARDO G. , LUDWIG THELMA A. V.
Published: August 2013

A new planktonic species of Urosolenia is described from Southern Brazilian reservoirs. Urosolenia obesa sp. nov. was found in several studied samples and the unique set of features led us to propose it as new and to compare their morphology with similar species found in the literature, as Rhizosolenia  naui, R. eriensis var. pusilla and Urosolenia parva. Urosolenia obesa differs from the other species mainly by sub-cylindrical frustules, conical valves, calyptra straight, positioned in right to oblique angle in relation to pervalvar axis, ornamented by longitudinal ribs and ending in two teeth and one ligula. Probably, the new species has a wider geographic distribution, since the small size and slightly silicified frustules make it difficult to visualize them by light microscopy analysis of samples.
Cunila jaliscana (Lamiaceae) a new species from Jalisco, Mexico
Authors: GARCÍA-PEÑA MARÍA DEL ROSARIO , GONZÁLEZ-GALLEGOS JESÚS GUADALUPE
Published: August 2013

Cunila jaliscana, an endemic species to Jalisco, Mexico, is described and illustrated. Morphologically similar to C. lythrifolia, it differs by its divaricate branches, smaller leaf blades, narrower inflorescences, bracts shorter than calyx, and white and erect flowers.
Twins are not alone: a recircumscription of Linnaea (Caprifoliaceae)
Authors: CHRISTENHUSZ MAARTEN J.M.
Published: August 2013

The genus Linnaea is reviewed and expanded to include the genera Abelia (excluding section Zabelia), Diabelia, Dipelta, Kolkwitzia and Vesalea, making it monophyletic and comprising 16 species. The history of the generic name is discussed. An updated description for the genus Linnaea is provided and new combinations or names for all taxa are provided in Linnaea.
A new species of Torenia (Linderniaceae) from Gabon, remarks on Torenia mannii Skan, and a key to the African and Madagascan Torenia species
Authors: Fischer Eberhard , Lachenaud Olivier
Published: August 2013

The new species Torenia daubyi from Gabon is described and illustrated. It is closely related to T. mannii from which it differs in the smaller and relatively broader leaves, the broader calyx wings, and the shorter corolla. From T. silvicola it differs in the acute calyx lobes, broader calyx wings, and the filaments of the abaxial stamens bearing a clavate appendage. A key to the African and Madagascan species of Torenia is provided and the rediscovery of Torenia mannii, hitherto only known from the type, is reported.