bluuebunny/crossref_metadata_2025 huggingface dataset:
Inpatient Weight Loss as a Precursor to Bariatric Surgery for Adolescents With Extreme Obesity
Authors: Koeck Emily , Davenport Katherine , Barefoot Leah C. , Qureshi Faisal G. , Davidow Daniel , Nadler Evan P.
Published: March 2013

Background. As the obesity epidemic takes its toll on patients stricken with the disease and our health care system, debate continues regarding the use of weight loss surgery and its long-term consequences, especially for adolescents. One subset of patients regarding whom there is increased controversy is adolescents with extreme obesity (BMI > 60 kg/m2) because the risk of complications in this weight category is higher than for others undergoing bariatric surgery. Several strategies have been suggested for this patient group, including staged operations, combined operations, intragastric balloon use, and endoluminal sleeve placement. However, the device options are often not available to adolescents, and there are no data regarding staged or combined procedures in this age group. Methods. All adolescents with BMI >60 kg/m2 referred to our program were evaluated for inpatient medical weight loss prior to laparoscopic sleeve gastrectomy. The program utilizes a multidisciplinary approach with a protein-sparing modified fast diet, exercise, and behavioral modification. Results. Three patients completed the program, and each achieved significant preoperative weight loss through the inpatient program and successfully underwent bariatric surgery. Conclusions. Presurgical weight loss via an inpatient program for adolescents with a BMI >60 kg/m2 results in total weight loss comparable to a primary surgical procedure alone, with the benefit of decreasing the perioperative risk.
A comparison of gel point for a glass/epoxy composite and a neat epoxy material during isothermal curing
Authors: Jakobsen J , Andreasen JH , Thomsen OT
Published: March 2013

Determination of gel point is important for a modelling assessment of residual stresses developed during curing of composite materials. Residual stresses in a composite structure may have a detrimental effect on its mechanical performance and compromise its integrity. In this article, the evolution in bending stiffness of a glass/epoxy composite material during an isothermal curing process is examined to identify different material stages and behaviour. Differential scanning calorimetry and dynamic mechanical analysis are used to analyse the material behaviour. Gelation is identified as a clear onset in bending stiffness, and vitrification is seen as a decrease in the bending stiffness rate. Often gel point predictions for composite materials are based on neat matrix measurements. However, the results presented in this article demonstrate that the gel point is affected by the presence of the fibre reinforcement.
E-WOM and Accommodation
Authors: Filieri Raffaele , McLeay Fraser
Published: March 2013

Online reviews (ORs) are continuing to foster a renewed spread of word-of-mouth in the travel industry. Travelers are increasingly using ORs to inform them about accommodations and other tourism-related products. As such, it is important to improve our understanding of the behavioral consequences of e-word-of-mouth. In this article, we adopt the elaboration likelihood model to identify what influences travelers to adopt information from ORs in their decision making. We measure the influence of six dimensions of information quality that are part of the central route and two dimensions that are associated with the peripheral route of persuasion. The results of this study reveal that product ranking, information accuracy, information value-added, information relevance, and information timeliness are strong predictors of travelers’ adoption of information from ORs on accommodations. These results imply that high-involvement travelers adopt both central (information quality) and peripheral (product ranking) routes when they process information from ORs.
Strategic Planning Research: Toward a Theory-Driven Agenda
Authors: Wolf Carola , Floyd Steven W.
Published: March 2013

This review incorporates strategic planning research conducted over more than 30 years and ranges from the classical model of strategic planning to recent empirical work on intermediate outcomes, such as the reduction of managers’ position bias and the coordination of subunit activity. Prior reviews have not had the benefit of more socialized perspectives that developed in response to Mintzberg’s critique of planning, including research on planned emergence and strategy-as-practice approaches. To stimulate a resurgence of research interest on strategic planning, this review therefore draws on a diverse body of theory beyond the rational design and contingency approaches that characterized research in this domain until the mid-1990s. We develop a broad conceptualization of strategic planning and identify future research opportunities for improving our understanding of how strategic planning influences organizational outcomes. Our framework incorporates the role of strategic planning practitioners; the underlying routines, norms, and procedures of strategic planning (practices); and the concrete activities of planners (praxis).
Comparison of Cardiac Troponin I and T, Including the Evaluation of an Ultrasensitive Assay, as Indicators of Doxorubicin-induced Cardiotoxicity
Authors: Reagan William J. , York Malcolm , Berridge Brian , Schultze Eric , Walker Dana , Pettit Syril
Published: March 2013

Cardiac troponin (cTn) has been utilized to assess acute myocardial injury, but the cTn response in active/ongoing chronic injury is not well documented. The purpose of this study was to characterize the cardiac troponin I (cTnI), cardiac troponin T (cTnT), high-sensitivity cTnI, hematology, and clinical chemistry responses in rats treated with doxorubicin. Rats treated with 1, 2, or 3 mg/kg/week (wk) of doxorubicin for 2, 4, or 6 wks were sacrificed after 0, 2, or 4 wks of recovery and compared to untreated controls and animals treated with doxorubicin/dexrazoxane (50 mg/kg/wk) or etoposide (1 and 3 mg/kg/wk). The incidence and mean magnitude of cTn response increased with increasing dose and/or duration of doxorubicin treatment. Conversely, dexrazoxane/doxorubicin was partially protective for cardiotoxicity, and minimal cardiotoxicity occurred with etoposide treatment. Both cTnI and cTnT effectively identified doxorubicin-induced injury as indicated by vacuolation of cardiomyocytes of the atria/ventricles. The association between the cTn responses and histological changes was greater at the higher total exposures, but the magnitude of cTn response did not match closely with histologic grade. The high-sensitivity cTnI assay was also effective in identifying cardiac injury. Alterations occurred in the hematology and clinical chemistry parameters and reflected both dose and duration of doxorubicin treatment.
Complex Histopathologic Response in Rat Kidney to Oral β-myrcene
Authors: Cesta Mark F. , Hard Gordon C. , Boyce John T. , Ryan Michael J. , Chan Po C. , Sills Robert C.
Published: March 2013

Oral gavage studies with β-myrcene in male F344 rats showed a complex renal pathology comprising both alpha2u-globulin (α2u-g) nephropathy, an unusual nephrosis involving the outer stripe of outer medulla (OSOM), and an increased incidence of renal tubule tumors by 2 years. In the 90-day and 2-year studies, respectively, α2u-g nephropathy and linear papillary mineralization were observed in males at the two lower doses but were absent from the high dose. Nephrosis was characterized by dilation of the S3 tubules, nuclear enlargement (including karyomegaly), and luminal pyknotic cells, all in the outermost OSOM. Nephrosis was minimal at the higher doses in the 90-day study, but progressed to a severe grade in males dosed with 1,000 mg/kg for 2 years. Renal tubule tumors developed in treated groups with incidences up to 30% in the 250 and 500 mg/kg male dose groups. Tumors at the lower doses in males may have been associated with α2u-g nephropathy, while those at higher doses in both sexes may have been due to the nephrosis. Because β-myrcene induced a complex spectrum of renal pathology, the α2u-g nephropathy mechanism cannot be the sole mechanism of carcinogenesis in these rats.
Panel 1: Epidemiology, Natural History, and Risk Factors
Authors: Hoffman Howard J. , Daly Kathleen A. , Bainbridge Kathleen E. , Casselbrant Margaretha L. , Homøe Preben , Kvestad Ellen , Kvaerner Kari Jorunn , Vernacchio Louis
Published: March 2013

Background

The First International Symposium on Recent Advances in Otitis Media (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been organized in the United States every 4 years since, followed by a research conference to (a) assess major research accomplishments, (b) identify important research questions and opportunities, (c) develop consensus on definitions and terminology, and (d) establish priorities with short‐ and long‐term research goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural History, and Risk Factors.

Objective

To provide a review of recent literature on the epidemiology, natural history, and risk factors for OM.

Data Sources and Review Methods

A search of OM articles in English published July 2007 to June 2011 was conducted using PubMed and related databases. Those with findings judged of importance for epidemiology, public health, and/or statistical methods were reviewed.

Results

The literature has continued to expand, increasing understanding of the worldwide burden of OM in childhood, complications from treatment failures, and comorbidities. Novel risk factors, including genetic factors, have been examined for OM susceptibility. Population‐based studies in Canada, the United States, and other countries confirmed reductions in OM prevalence. Although most studies concentrated on acute OM (AOM) or OM with effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major public health problem in developing countries and for certain indigenous populations around the world.

Conclusions and Implications for Practice

Recent publications have reinforced earlier epidemiological findings, while extending our knowledge in human population groups with high burden of OM.
Panel 8: Complications and Sequelae
Authors: Jung Timothy T. K. , Alper Cuneyt M. , Hellstrom Sten O. , Hunter Lisa L. , Casselbrant Margaretha L. , Groth Anita , Kemaloglu Yusuf K. , Kim Sang Gyoon , Lim David , Nittrouer Susan , Park Kee Hyun , Sabo Diane , Spratley Jorge
Published: March 2013

Background and Objectives

Although serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state‐of‐the‐art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development.

Data Sources

Primarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database.

Review Methods

All types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report.

Results

Key findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae.

Conclusion and Implications for Practice

Over the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.
Panel 2: Eustachian Tube, Middle Ear, and Mastoid—Anatomy, Physiology, Pathophysiology, and Pathogenesis
Authors: Swarts J. Douglas , Alper Cuneyt M. , Luntz Michal , Bluestone Charles D. , Doyle William J. , Ghadiali Samir N. , Poe Dennis S. , Takahashi Haruo , Tideholm Bo
Published: March 2013

Objective

This report reviews the literature to identify the advances in our understanding of the middle ear (ME)–Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short‐term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research.

Data Sources

Databases searched included PubMed, Web of Science (1945‐present), Medline (1950 to present), Biosis Previews (1969‐present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012.

Review Methods

The panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short‐term goals proposed.

Conclusions

Progress was made on 16 of the 19 short‐term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction.

Implications for Practice

In the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.
Charting changes in commitment
Authors: Dailey René M. , Brody Nicholas , LeFebvre Leah , Crook Brittani
Published: March 2013

The present study examined how turning points reported by individuals in on-again/off-again (on–off) relationships reflected relationship trajectories. Participants ( N = 581) completed an online Retrospective Interview Technique asking them to report on up to 10 turning points. Participants indicated their commitment level at each turning point. Based on the variations in commitment across turning points, five trajectories emerged. Trajectory groups were compared regarding relational stability factors. Results suggest that on–off partners with a steady-low commitment trajectory reported less stability than individuals with steady-high commitment. Additionally, partners in the fluctuating trajectory, which would seemingly represent less stability, reported moderate perceptions of their relationships, faring better than the low-steady commitment group. Overall, findings add to an understanding of how to best characterize on–off relationships.
A piezoelectric direct-drive servo valve with a novel multi-body contacting spool-driving mechanism: Design, modelling and experiment
Authors: Changbin Guan , Zongxia Jiao
Published: March 2013

Stack-type piezoelectric actuators, which usually consist of several ceramic layers connected in series, are widely used in piezoelectric direct-drive servo valves (PDDSV). However, poor pulling force capacity of this kind of actuators affects the performances of the direct-drive servo valves. This article presents a new type of PDDSV, whose spool-driving mechanism is composed of a set of independent parts that are not fixed together but are in contact with each other. This multi-body contacting spool-driving mechanism provides bidirectional movement of the spool by a preloaded stack-type piezoelectric actuator and a driving disc spring. This prevents the stack-type piezoelectric actuator from bearing the pulling force due to the inertia and friction of the spool. Design of the proposed servo valve is illustrated in detail and its characteristics are also predicted. Based on a nonlinear dynamic model of the multi-body contacting spool-driving mechanism, a comprehensive dynamic simulation model of the proposed PDDSV is established. Static and dynamic characteristics of the proposed PDDSV have been studied experimentally and good agreements between experimental and simulation results are observed. The dynamic performances of the proposed PDDSV are compared with the existing piezoelectric servo valves, which demonstrate that the proposed PDDSV has satisfactory dynamic characteristics for high-frequency applications.
Total hip arthroplasty by using a cementless ultrashort stem: A subject-specific finite element analysis for a young patient clinical case
Authors: Epasto Gabriella , Foti Albina , Guglielmino Eugenio , Rosa Michele A
Published: March 2013

In this article, a subject-specific finite element analysis has been developed to study a clinical case of a surgically misaligned hip prosthesis with an ultrashort stem. It was set out to study the strain energy density pattern, comparing the results obtained with computed tomography images. The authors developed two other numerical models: the first one analyzes the stress and strain distributions in the healthy femur (without prosthesis) and the second one analyzes the same boneimplant biomechanical system of the clinical case but assuming the prosthesis in the proper position. The misaligned prosthesis produced an overload at the proximal posterior plane of the femur, as confirmed by computed tomography images, which detect the formation of new bone. The numerical model of the correctly positioned prosthesis demonstrated that the bone is not overloaded and that the position of neutral axis does not significantly shift from the physiological condition.
Will politics be tweeted? New media use by Iranian youth in 2011
Authors: Wojcieszak Magdalena , Smith Briar
Published: March 2013

The uprisings after the 2009 elections in Iran generated debate on new media’s potential to affect dissent in authoritarian countries. We surveyed 2800 young, educated, metropolitan, and technologically savvy Iranians over a year after the election and during the uprisings in the Middle East and North Africa to examine what sources these youth use for information, the extent to which they rely on new media for political exchanges, their experiences with online censorship, and political efficacy as related to new media. Although the Internet was stated as the most important news outlet, state-controlled television was often used, and Twitter was the least prevalent new media platform. Personal issues and IT/science were more often discussed via new media than politics. Further, it was using new media, not talking politics online, that predicted the frequency with which respondents encountered blocked websites online and also perceptions of their ownpolitical efficacy. Although our findings may support voices that are skeptical about technology’s ability to sustain revolution, we also identify what can be described as hubs of politicized Iranian youth.
(Il)Legitimisation of the role of the nation state: Understanding of and reactions to Internet censorship in Turkey
Authors: Yalkin Çağri , Kerrigan Finola , vom Lehn Dirk
Published: March 2013

This study aims to explore Turkish citizen-consumers’ understanding of and reactions to censorship of websites in Turkey by using in-depth interviews and online ethnography. In an environment where sites such as YouTube and others are increasingly being banned, the citizen-consumers’ macro-level understanding is that such censorship is part of a wider ideological plan and their micro-level understanding is that their relationship with the wider global network is reduced, in the sense that they have trouble accessing full information on products, services and experiences. The study revealed that citizen-consumers engage in two types of resistance strategies against such domination by the state: using irony as passive resistance, and using the very same technology used by the state to resist its domination.
Cartograms via mathematical morphology
Authors: Sagar B S Daya
Published: March 2013

Visualization of geographic variables as spatial objects of size proportional to variable strength is possible via generating cartograms. We developed a methodology based on mathematical morphology to generate contiguous cartograms. This methodology relies on weighted skeletonization by zone of influence. This weighted skeletonization by zone of influence determines the points of contact of multiple frontlines propagating from centroids of various planar sets (states) at the traveling rates depending upon the variable’s strength. The contiguous cartogram generated via this morphology-based algorithm preserves the global shape and local shapes and yields minimal area errors. We generated a cartogram for a population variable to demonstrate the proposed approach. Furthermore, the population cartograms for the United States generated via four other approaches are compared with the morphology-based cartogram in terms of errors with respect to area, local shape, and global shape. This approach for generating cartograms preserves the global shape at the expense of compromising with area errors. It is inferred from the comparative error analysis that the proposed morphology-based approach could be further extended by exploring the applicability of additional characteristics of B, which controls the dilation propagation speed and direction of dilation while performing weighted skeletonization by zone of influence, to minimize the local shape errors and area errors.
Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ
Authors: Guinane Caitriona M. , Cotter Paul D.
Published: March 2013

The human gut microbiota has become the subject of extensive research in recent years and our knowledge of the resident species and their potential functional capacity is rapidly growing. Our gut harbours a complex community of over 100 trillion microbial cells which influence human physiology, metabolism, nutrition and immune function while disruption to the gut microbiota has been linked with gastrointestinal conditions such as inflammatory bowel disease and obesity. Here, we review the many significant recent studies that have centred on further enhancing our understanding of the complexity of intestinal communities as well as their genetic and metabolic potential. These have provided important information with respect to what constitutes a ‘healthy gut microbiota’ while furthering our understanding of the role of gut microbes in intestinal diseases. We also highlight recently developed genomic and other tools that are used to study the gut microbiome and, finally, we consider the manipulation of the gut microbiota as a potential therapeutic option to treat chronic gastrointestinal disease.
Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells
Authors: van Balkom Bas W. M. , de Jong Olivier G. , Smits Michiel , Brummelman Jolanda , den Ouden Krista , de Bree Petra M. , van Eijndhoven Monique A. J. , Pegtel D. Michiel , Stoorvogel Willem , Würdinger Thomas , Verhaar Marianne C.
Published: March 2013

Key Points

Endothelial cells secrete exosomes containing miR-214, which suppress senescence and stimulates an angiogenic program in target cells. Exosomal miR-214 regulates ataxia telangiectasia mutated expression in recipient endothelial cells.
Computing minimal nutrient sets from metabolic networks via linear constraint solving
Authors: Eker Steven , Krummenacker Markus , Shearer Alexander G , Tiwari Ashish , Keseler Ingrid M , Talcott Carolyn , Karp Peter D
Published: March 2013

Background

As more complete genome sequences become available, bioinformatics challenges arise in how to exploit genome sequences to make phenotypic predictions. One type of phenotypic prediction is to determine sets of compounds that will support the growth of a bacterium from the metabolic network inferred from the genome sequence of that organism.

Results

We present a method for computationally determining alternative growth media for an organism based on its metabolic network and transporter complement. Our method predicted 787 alternative anaerobic minimal nutrient sets for Escherichia coli K-12 MG1655 from the EcoCyc database. The program automatically partitioned the nutrients within these sets into 21 equivalence classes, most of which correspond to compounds serving as sources of carbon, nitrogen, phosphorous, and sulfur, or combinations of these essential elements. The nutrient sets were predicted with 72.5% accuracy as evaluated by comparison with 91 growth experiments. Novel aspects of our approach include (a) exhaustive consideration of all combinations of nutrients rather than assuming that all element sources can substitute for one another(an assumption that can be invalid in general) (b) leveraging the notion of a machinery-duplicating constraint, namely, that all intermediate metabolites used in active reactions must be produced in increasing concentrations to prevent successive dilution from cell division, (c) the use of Satisfiability Modulo Theory solvers rather than Linear Programming solvers, because our approach cannot be formulated as linear programming, (d) the use of Binary Decision Diagrams to produce an efficient implementation.

Conclusions

Our method for generating minimal nutrient sets from the metabolic network and transporters of an organism combines linear constraint solving with binary decision diagrams to efficiently produce solution sets to provided growth problems.
Genetic variants in PARP1 (rs3219090) and IRF4(rs12203592) genes associated with melanoma susceptibility in a Spanish population
Authors: Peña-Chilet Maria , Blanquer-Maceiras Maite , Ibarrola-Villava Maider , Martinez-Cadenas Conrado , Martin-Gonzalez Manuel , Gomez-Fernandez Cristina , Mayor Matias , Aviles Juan Antonio , Lluch Ana , Ribas Gloria
Published: March 2013

Background

Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition.

Methods

We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics.

Results

We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study.

Conclusions

To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection.
A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values
Authors: Jin Guang-Zhi , Dong Hui , Yu Wen-Long , Li Yan , Lu Xin-Yuan , Yu Hua , Xian Zhi-Hong , Dong Wei , Liu Yin-Kun , Cong Wen-Ming , Wu Meng-Chao
Published: March 2013

Background

Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists.

Methods

The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients.

Results

ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence.

Conclusions

ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
Enhanced transgene expression in rice following selection controlled by weak promoters
Authors: Zhou Jie , Yang Yong , Wang Xuming , Yu Feibo , Yu Chulang , Chen Juan , Cheng Ye , Yan Chenqi , Chen Jianping
Published: March 2013

Background

Techniques that enable high levels of transgene expression in plants are attractive for the commercial production of plant-made recombinant pharmaceutical proteins or other gene transfer related strategies. The conventional way to increase the yield of desired transgenic products is to use strong promoters to control the expression of the transgene. Although many such promoters have been identified and characterized, the increase obtainable from a single promoter is ultimately limited to a certain extent.

Results

In this study, we report a method to magnify the effect of a single promoter by using a weak promoter-based selection system in transgenic rice. tCUP1, a fragment derived from the tobacco cryptic promoter (tCUP), was tested for its activity in rice by fusion to both a β-glucuronidase (GUS) reporter and a hygromycin phosphotransferase (HPT) selectable marker. The tCUP1 promoter allowed the recovery of transformed rice plants and conferred tissue specific expression of the GUS reporter, but was much weaker than the CaMV 35S promoter in driving a selectable marker for growth of resistant calli. However, in the resistant calli and regenerated transgenic plants selected by the use of tCUP1, the constitutive expression of green fluorescent protein (GFP) was dramatically increased as a result of the additive effect of multiple T-DNA insertions. The correlation between attenuated selection by a weak promoter and elevation of copy number and foreign gene expression was confirmed by using another relatively weak promoter from nopaline synthase (Nos).

Conclusions

The use of weak promoter derived selectable markers leads to a high T-DNA copy number and then greatly increases the expression of the foreign gene. The method described here provides an effective approach to robustly enhance the expression of heterogenous transgenes through copy number manipulation in rice.
Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents
Authors: Muhammad Naveed , Rehman Najeeb ur , Khan Haroon , Saeed Muhammad , Gilani Anwarul-Hassan
Published: March 2013

Background

The present study was aimed to provide ethnopharmacological basis for the medicinal use of Viola betonicifolia whole plant in indigestion and constipation.

Methods

Mice were used in in-vivo prokinetic and laxative studies while in-vitro experiments were conducted on isolated tissues of rabbit and guinea-pig gut preparations suspended in a tissue bath to measure isotonic contractions.

Results

The crude methanolic extract of Viola betonicifolia (VBME) showed partially atropine-sensitive prokinetic (50 and 100 mg/kg) and laxative (30 and 100 mg/kg) activities in mice. When tested in isolated rabbit jejunum and guinea-pig ileum, VBME caused dose-dependent contractions at 0.01-0.3 mg/mL and 0.03-5 mg/mL, respectively. The spasmogenic effect was partially sensitive to atropine, while the presence of pyrilamine, SB203186 or hexamethonium had no effect in both gut preparations. VBME partially inhibited acetylcholinesterase enzyme (19%) in the in-vitro assay. The spasmodic effect of VBME was more efficacious in guinea-pig ileum than rabbit jejunum preparation. The phytochemical analysis of the crude methanolic extract for total alkaloids and saponins revealed that the VBME is a rich source of alkaloids and saponins.

Conclusions

This study showed the prokinetic and laxative effects of Viola betonicifolia in mice, partially mediated through cholinergic action. The in-vitro spasmodic effect of the plant extract was also partially sensitive to atropine indicating more than one mechanisms in the gut stimulant effect. This study provides a rationale for the medicinal use of Viola betonicifolia in indigestion and constipation.
Type 1 diabetes mellitus abrogates compensatory augmentation of myocardial neuregulin-1β/ErbB in response to myocardial infarction resulting in worsening heart failure
Authors: Odiete Oghenerukevwe , Konik Ewa A , Sawyer Douglas B , Hill Michael F
Published: March 2013

Background

Diabetes mellitus (DM) patients surviving myocardial infarction (MI) exhibit a substantially higher incidence of subsequent heart failure (HF). Neuregulin (NRG)-1 and erythroblastic leukemia viral oncogene homolog (ErbB) receptors have been shown to play a critical role in maintenance of cardiac function. However, whether myocardial NRG-1/ErbB is altered during post-MI HF associated with DM remains unknown. The aim of this study was to determine the impact of type 1 DM on the myocardial NRG-1/ErbB system following MI in relation to residual left ventricular (LV) function.

Methods

Type 1 DM was induced in rats via administration of streptozotocin (65 mg/kg, i.p.). Control rats were injected with citrate buffer (vehicle) only. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by ligation of the left coronary artery. Sham MI rats underwent the same surgical procedure with the exception that the left coronary artery was not ligated. At 4 weeks after surgery, residual in vivo LV function was assessed via echocardiography. Myocardial protein expression of NRG-1β, ErbB2 and ErbB4 receptors, and MDM2 (a downstream signaling pathway induced by NRG-1 that has been implicated in cell survival) was assessed in the remaining, viable LV myocardium by Western blotting. Changes in ErbB receptor localization in the surviving LV myocardium of diabetic and non-diabetic post-MI rats was determined using immunohistochemistry techniques.

Results

At 4 weeks post-MI, echocardiography revealed that LV fractional shortening (FS) and LV ejection fraction (EF) were significantly lower in the DM + MI group compared to the MI group (LVFS: 17.9 ± 0.7 vs. 25.2 ± 2.2; LVEF: 35.5 ± 1.4 vs. 47.5 ± 3.5, respectively; P < 0.05), indicating an increased functional severity of HF among the DM + MI rats. Up-regulation of NRG-1β and ErbB2 protein expression in the MI group was abrogated in the DM + MI group concurrent with degradation of MDM2, a downstream negative regulator of p53. ErbB2 and ErbB4 receptors re-localized to cardiac myocyte nuclei in failing type 1 diabetic post-MI hearts.

Conclusions

Type 1 DM prevents compensatory up-regulation of myocardial NRG-1/ErbB after MI coincident with an increased severity of HF.
Comparing the angiogenic potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells
Authors: Dao Mo , Tate Ciara C , McGrogan Michael , Case Casey C
Published: March 2013

Background

Angiogenesis is a critical part of the endogenous repair process in brain injury and disease, and requires at least two sequential steps. First, angiogenic sprouting of endothelial cells occurs, which entails the initial proliferation of endothelial cells and remodeling of the surrounding extracellular matrix. Second, vessel stabilization is necessary to prevent vascular regression, which relies on vascular smooth muscle recruitment to surround the young vessels. Marrow stromal cells (MSCs) have been shown to promote revascularization after hindlimb ischemia, cardiac ischemia, and stroke. SB623 cells are derived from marrow stromal cells by transfection with a Notch1 intracellular domain (NICD)-expressing plasmid and are known to elicit functional improvement in experimental stroke. These cells are currently used in human clinical testing for treatment of chronic stroke. In the current study, the angiogenic property of SB623 cells was investigated using cell-based assays.

Methods

Angiogenic paracrine factors secreted by SB623 cells and the parental MSCs were identified using the Qantibody Human Angiogenesis Array. To measure the angiogenic activity of conditioned medium from SB623 cells and MSCs, endothelial tube formation in the human umbilical vein endothelial cell (HUVEC) assay and endothelial cell sprouting and branching in the rodent aortic ring assay were quantified. To validate the angiogenic contribution of VEGF in conditioned medium, endothelial cells and aortic rings were treated with SU5416, which inhibits VEGFR2 at low dose.

Results

Conditioned medium from SB623 cells promoted survival and proliferation of endothelial cells under serum-deprived conditions and supports HUVEC vascular tube formation. In a rodent aortic ring assay, there was enhanced endothelial sprouting and branching in response to SB623-derived conditioned medium. SU5416 treatment partially reversed the effect of conditioned medium on endothelial cell survival and proliferation while completely abrogate HUVEC tube formation and endothelial cell sprouting and branching in aortic ring assays.

Conclusions

These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.
Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis
Authors: Arampatzis Spyridon , Funk Georg-Christian , Leichtle Alexander Benedikt , Fiedler Georg-Martin , Schwarz Christoph , Zimmermann Heinz , Exadaktylos Aristomenis Konstantinos , Lindner Gregor
Published: March 2013

Background

Diuretics are among the most commonly prescribed medications and, due to their mechanisms of action, electrolyte disorders are common side effects of their use. In the present work we investigated the associations between diuretics being taken and the prevalence of electrolyte disorders on admission as well as the impact of electrolyte disorders on patient outcome.

Methods

In this cross sectional analysis, all patients presenting between 1 January 2010 and 31 December 2011 to the emergency room (ER) of the Inselspital, University Hospital Bern, Switzerland were included. Data on diuretic medication, baseline characteristics and laboratory data including electrolytes and renal function parameters were obtained from all patients. A multivariable logistic regression model was performed to assess the impact of factors on electrolyte disorders and patient outcome.

Results

A total of 8.5% of patients presenting to the ER used one diuretic, 2.5% two, and 0.4% three or four. In all, 4% had hyponatremia on admission and 12% hypernatremia. Hypokalemia was present in 11% and hyperkalemia in 4%. All forms of dysnatremia and dyskalemia were more common in patients taking diuretics. Loop diuretics were an independent risk factor for hypernatremia and hypokalemia, while thiazide diuretics were associated with the presence of hyponatremia and hypokalemia. In the Cox regression model, all forms of dysnatremia and dyskalemia were independent risk factors for in hospital mortality.

Conclusions

Existing diuretic treatment on admission to the ER was associated with an increased prevalence of electrolyte disorders. Diuretic therapy itself and disorders of serum sodium and potassium were risk factors for an adverse outcome.
Protective and therapeutic potency of N-acetyl-cysteine on propionic acid-induced biochemical autistic features in rats
Authors: Aldbass Abeer M , Bhat Ramesa Shafi , El-Ansary Afaf
Published: March 2013

Background

The investigation of the environmental contribution for developmental neurotoxicity is very critical. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations towards identifying either environmental toxicants that cause or drugs that protect from neurotoxicity and may help in treatment of neurodevelopmental disorders.

Objective

To study both the protective and therapeutic effects of N-acetyl cysteine on brain intoxication induced by propionic acid (PPA) in rats.

Methods

Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups, each of 7 animals. Group 1: control group, orally received only phosphate buffered saline; Group 2: PPA-treated group, received a neurotoxic dose of of PPA of 250 mg/kg body weight/day for 3 days; Group 3: protective group, received a dose of 50 mg/kg body weight/day N-acetyl-cysteine for one week followed by a similar dose of PPA for 3 days; and Group 4: therapeutic group, treated with the same dose of N-acetyl cysteine after being treated with the toxic dose of PPA. Serotonin, interferon gamma (IFN-γ), and glutathione-s-transferase activity, together with Comet DNA were assayed in the brain tissue of rats in all different groups.

Results

The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of serotonin (5HT), increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally Comet DNA assay showed remarkably higher tail length, tail DNA % damage and tail moment. N-acetyl-cysteine was effective in counteracting the neurotoxic effects of PPA.

Conclusions

The low dose and the short duration of N-acetyl-cysteine treatment tested in the present study showed much more protective rather than therapeutic effects on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration in the impaired biochemical parameters representing neurochemical, inflammatory, detoxification and DNA damage processes.
Comparison of whole blood and PBMC assays for T-cell functional analysis
Authors: Deenadayalan Anbarasu , Maddineni Prabhavathi , Raja Alamelu
Published: March 2013

Background

Tuberculosis remains the foremost cause of morbidity and mortality, more than any other single infectious disease in the world. Cell mediated immune response plays a crucial role in the control of tuberculosis. Therefore, measuring cell mediated immune response against the antigens is having a vital role in understanding the pathogenesis of tuberculosis, which will also help in the diagnosis of and vaccination for tuberculosis.

Findings

The aim of the present study was to compare and optimize the assay conditions to measure the cell mediated immune response against M. tuberculosis specific antigens. Because the conventional PBMC assays (due to requirement of large volume of blood sample) are unable to screen more number of antigens within the same blood sample. So, here we have compared 6 days culture supernatants of 1:5 and 1:10 diluted blood and PBMCs from healthy laboratory volunteers, to assess the proliferative response of T lymphocytes and secreted IFN-γ levels against purified recombinant antigen of M. tuberculosis (MPT51, Rv3803c), crude antigens of M. tuberculosis (PPD) and mitogen (PHA).

Conclusions

We have observed good correlation between each assay and also the mean difference of these assays did not reach the statistical significance (p > 0.05). From these results, we conclude that 1:10 diluted whole-blood cultures can be well-suited as an alternative assay to measure cytokine production and lymphocyte proliferation in comparison to the conventional PBMC assays. Moreover, 1:10 diluted blood assays require less volume of blood when compared to PBMC assays which will be useful particularly in paediatric and field studies in endemic countries, where blood volume is a limiting factor.
Estimation of total phenol and in vitro antioxidant activity of Albizia procera leaves
Authors: khatoon Mahfuza , Islam Ekramul , Islam Rafikul , Rahman Aziz Abdur , Alam AHM Khurshid , Khondkar Proma , Rashid Mamunur , Parvin Shahnaj
Published: March 2013

Background

Research on natural products has gained a wide popularity due to the potential of discovering active compounds. The antioxidant properties contained in plants have been proposed as one of the mechanisms for the observed beneficial effect. Therefore, the present study investigated the antioxidant activity and total phenolic contents of various solvent extracts of Albizia procera leaves.

Methods

Antioxidant activity of the methanol extract and its derived fractions petroleum ether (APP), carbon tetrachloride (APC), dichloromethane (APD), ethyl acetate (APE), and residual aqueous fraction (APA) of the leaves of Albizia procera was performed by in vitro chemical analyses. Total phenolic content of the APM and other five fractions were also determined. APM and its derived fractions were also subjected to preliminary phytochemical screening test for various constituents.

R esults

Phytochemical screening revealed the presence of saponins, steroids, tannins, glycosides and flavonoids in the extracts. Amongst the extracts, APE showed the highest total phenolic content (449.18 ± 18.41mg of gallic acid equivalent/g of extract). In DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging test, the IC50 value of APM, APP, APC, APD, APE and APA was 43.43, 63.60, 166.18, 41.15, 11.79, and 63.06 μg/mL, respectively. Therefore, among the APM and its derived fractions, APE showed the highest antioxidant activity which is comparable to that of standard ascorbic acid (AA) (IC50 10.12 μg/mL). The total antioxidant capacity was found to be varied in different fractions. The reducing activity on ferrous ion was ranked as APE > APD > APM > APA > APC.

C onclusion

The above evidences suggest that APE of A. procera leaf is a potential source of natural antioxidant and can be used to prevent diseases associated with free radicals.