bluuebunny/crossref_metadata_2025 huggingface dataset:
Population dynamics of the southern short-tailed opossum (Monodelphis dimidiata) in the Pampas of Argentina
Authors: Baladrón Alejandro V. , Malizia Ana I. , Bó María S. , Liébana María S. , Bechard Marc J.
Published: November 2012

The genus Monodelphis is one of the most species rich among Neotropical marsupials. Despite this, little is known about most of the species. One of the most enigmatic species is M. dimidiata, a small terrestrial opossum that inhabits the Pampean region of Argentina, which is suspected to be a semelparous breeder. From 2005 to 2008, we conducted seasonal live trapping in near-pristine marshy grasslands and agroecosystems of the Pampean region in order to evaluate the population trends of this species and the occurrence of semelparity. M. dimidiata was characterised by a low abundance in the study area. The average density was higher in grasslands than in agroecosystems, and it appeared to be influenced by vegetative cover. The onset of the breeding season occurred during spring when the opossums showed a sudden increase in body size. Given that mature individuals were not found beyond autumn, the findings suggest an annual cycle for this species. In addition, this abrupt maturation resulted in a pronounced sexual dimorphism that, together with the strong reproductive seasonality and a likely polygynous mating system, supported previous claims that the species is semelparous. Our results also emphasise the importance of native grassland habitat for the maintenance of stable populations of M. dimidiata.
Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells
Authors: Tsang Chi Man , Yip Yim Ling , Lo Kwok Wai , Deng Wen , To Ka Fai , Hau Pok Man , Lau Victoria Ming Yi , Takada Kenzo , Lui Vivian Wai Yan , Lung Maria Li , Chen Honglin , Zeng Musheng , Middeldorp Jaap Michiel , Cheung Annie Lai-Man , Tsao Sai Wah
Published: November 2012

Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4
R24C
) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.
Rational design of potent domain antibody inhibitors of amyloid fibril assembly
Authors: Ladiwala Ali Reza A. , Bhattacharya Moumita , Perchiacca Joseph M. , Cao Ping , Raleigh Daniel P. , Abedini Andisheh , Schmidt Ann Marie , Varkey Jobin , Langen Ralf , Tessier Peter M.
Published: November 2012

Antibodies hold significant potential for inhibiting toxic protein aggregation associated with conformational disorders such as Alzheimer’s and Huntington’s diseases. However, near-stoichiometric antibody concentrations are typically required to completely inhibit protein aggregation. We posited that the molecular interactions mediating amyloid fibril formation could be harnessed to generate antibodies with potent antiaggregation. Here we report that grafting small amyloidogenic peptides (6–10 residues) into the complementarity-determining regions of a single-domain (V
H
) antibody yields potent domain antibody inhibitors of amyloid formation. Grafted AMyloid-Motif AntiBODIES (gammabodies) presenting hydrophobic peptides from Aβ (Alzheimer’s disease), α-Synuclein (Parkinson's disease), and islet amyloid polypeptide (type 2 diabetes) inhibit fibril assembly of each corresponding polypeptide at low substoichiometric concentrations (1:10 gammabody:monomer molar ratio). In contrast, sequence- and conformation-specific antibodies that were obtained via immunization are unable to prevent fibrillization at the same substoichiometric concentrations. Gammabodies prevent amyloid formation by converting monomers and/or fibrillar intermediates into small complexes that are unstructured and benign. We expect that our antibody design approach—which eliminates the need for immunization or screening to identify sequence-specific domain antibody inhibitors—can be readily extended to generate potent aggregation inhibitors of other amyloidogenic polypeptides linked to human disease.
Phycoerythrin-specific bilin lyase–isomerase controls blue-green chromatic acclimation in marineSynechococcus
Authors: Shukla Animesh , Biswas Avijit , Blot Nicolas , Partensky Frédéric , Karty Jonathan A. , Hammad Loubna A. , Garczarek Laurence , Gutu Andrian , Schluchter Wendy M. , Kehoe David M.
Published: November 2012

The marine cyanobacteriumSynechococcusis the second most abundant phytoplanktonic organism in the world's oceans. The ubiquity of this genus is in large part due to its use of a diverse set of photosynthetic light-harvesting pigments called phycobiliproteins, which allow it to efficiently exploit a wide range of light colors. Here we uncover a pivotal molecular mechanism underpinning a widespread response among marineSynechococcuscells known as “type IV chromatic acclimation” (CA4). During this process, the pigmentation of the two main phycobiliproteins of this organism, phycoerythrins I and II, is reversibly modified to match changes in the ambient light color so as to maximize photon capture for photosynthesis. CA4 involves the replacement of three molecules of the green light-absorbing chromophore phycoerythrobilin with an equivalent number of the blue light-absorbing chromophore phycourobilin when cells are shifted from green to blue light, and the reverse after a shift from blue to green light. We have identified and characterized MpeZ, an enzyme critical for CA4 in marineSynechococcus. MpeZ attaches phycoerythrobilin to cysteine-83 of the α-subunit of phycoerythrin II and isomerizes it to phycourobilin.mpeZRNA is six times more abundant in blue light, suggesting that its proper regulation is critical for CA4. Furthermore,mpeZmutants fail to normally acclimate in blue light. These findings provide insights into the molecular mechanisms controlling an ecologically important photosynthetic process and identify a unique class of phycoerythrin lyase/isomerases, which will further expand the already widespread use of phycoerythrin in biotechnology and cell biology applications.
Conversational perspective of therapeutic outcomes: The importance of preference in the development of discourse
Authors: Sutherland Olga A. , Sametband Inés , Silva Joaquín Gaete , Couture Shari J. , Strong Tom
Published: November 2012

Major theme: Evaluation of therapeutic outcome. Logical development of the theme: We suggest a way for practitioners and researchers to assess if they are on track in conversing towards client preferred goals. We offer a critique of more conventional approaches to studying therapeutic progress, suggesting how a discursive (i.e. focused on interaction and language use) lens can address these limitations. Through this lens we examine therapeutic progress evident in ‘preference work’, where clients demonstrably indicate, imply, agree and disagree with where the therapeutic conversation is heading. Such ‘preference work’ offers a form of evidence of within‐session outcomes in a process of reaching larger client preferred outcomes. Authors’ point of view: We present the results of conversation analysis – a qualitative approach to the study of therapy – to illustrate our discursive perspective on therapy progress and change. Implications: we suggest a way for practitioners to assess if they are on track in conversing towards client preferred goals. We propose that our interactional perspective may significantly contribute to bridging practice and research in therapy.
The End of Farm Labor Abundance
Authors: Taylor J. Edward , Charlton Diane , Yúnez‐Naude Antonio
Published: November 2012

An analysis of nationally representative panel data from rural Mexico, with observations in years 2002, 2007, and 2010, suggests that the same shift out of farm work that characterized U.S. labor history is well underway in Mexico. Meanwhile, the demand for agricultural labor in Mexico is rising. In the future, U.S. agriculture will compete with Mexican farms for a dwindling supply of farm labor. Since U.S. domestic workers are unwilling to do farm work and the United States can feasibly import farm workers from only a few countries in close geographic proximity, the agricultural industry will eventually need to adjust production to use less labor. The decline in foreign labor supply to farms in the United States ultimately will need to be accompanied by farm labor conservation, switching to less labor intensive crops and technologies, and labor management practices that match fewer workers with more farm jobs.
Front‐of‐Package Nutritional Labels and Consumer Beverage Perceptions
Authors: Kim Hyeyoung , House Lisa A. , Rampersaud Gail , Gao Zhifeng
Published: November 2012

The pressure to find solutions for high rates of obesity and overweight in the U.S. population has led industry groups to introduce voluntary front‐of‐package (FOP) nutritional labeling for beverages. This research examines the impact of these labels on consumers' perceptions of the healthiness of beverages. Though consumers reacted differently depending on the information in the label, in general, the perception of milks and 100% juices decreased, while perception of soft drinks and less than 100% juice drinks increased. If the purpose of FOP labels is to encourage healthier choices, the changes observed appear to be at odds with the goal.
Largenet2: an object-oriented programming library for simulating large adaptive networks
Authors: Zschaler Gerd , Gross Thilo
Published: November 2012

Summary: The largenet2 C++ library provides an infrastructure for the simulation of large dynamic and adaptive networks with discrete node and link states.

Availability: The library is released as free software. It is available at http://biond.github.com/largenet2. Largenet2 is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License.

Contact:  gerd@biond.org.
VAGUE: a graphical user interface for the Velvet assembler
Authors: Powell David R. , Seemann Torsten
Published: November 2012

Summary: Velvet is a popular open-source de novo genome assembly software tool, which is run from the Unix command line. Most of the problems experienced by new users of Velvet revolve around constructing syntactically and semantically correct command lines, getting input files into acceptable formats and assessing the output. Here, we present Velvet Assembler Graphical User Environment (VAGUE), a multi-platform graphical front-end for Velvet. VAGUE aims to make sequence assembly accessible to a wider audience and to facilitate better usage amongst existing users of Velvet.

Availability and implementation: VAGUE is implemented in JRuby and targets the Java Virtual Machine. It is available under an open-source GPLv2 licence from http://www.vicbioinformatics.com/.

Contact:  torsten.seemann@monash.edu
VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue
Authors: Chen Yunxin , Yao Hui , Thompson Erika J. , Tannir Nizar M. , Weinstein John N. , Su Xiaoping
Published: November 2012

Summary: We developed a new algorithmic method, VirusSeq, for detecting known viruses and their integration sites in the human genome using next-generation sequencing data. We evaluated VirusSeq on whole-transcriptome sequencing (RNA-Seq) data of 256 human cancer samples from The Cancer Genome Atlas. Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity. VirusSeq can also perform this function using whole-genome sequencing data of human tissue.

Availability: VirusSeq has been implemented in PERL and is available at http://odin.mdacc.tmc.edu/∼xsu1/VirusSeq.html.

Contact:  xsu1@mdanderson.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
NetCAD: a network analysis tool for coronary artery disease-associated PPI network
Authors: Ren Guomin , Liu Zhihua
Published: November 2012

Summary: The systematic and unbiased charting of protein–protein interaction (PPI) networks relevant to health or diseases has become an important and burgeoning challenge in systems biology. Further, current reports have supported that good correlation exists between the topological properties and biological function of protein nodes in networks. Coronary artery disease (CAD, also called coronary heart disease) is the most common type of heart disease worldwide. Traditional approaches of studying individual gene or protein have shown their weakness in such complex disease. Here, we provide NetCAD, a web-based tool for systematic investigation of CAD-specific proteins in human PPI network. The features of NetCAD includes the following: proposing a novel method combining biological principles and graph theory, quantified topological analysis tools, build-in PPI information database consolidated from major public databases, creating CAD-associated subnetwork and visualizing network graph with good visual effects. NetCAD may provide important biological information for uncovering the molecular mechanisms and potential targets for therapies of CAD, which could not be found merely through molecular biology methods.

Availability and implementation: NetCAD is freely available at: http://www.herbbol.org/netcad/.

Contact:  zhliu@implad.ac.cn or zhliu.liulab@foxmail.com
Drug–target interaction prediction by learning from local information and neighbors
Authors: Mei Jian-Ping , Kwoh Chee-Keong , Yang Peng , Li Xiao-Li , Zheng Jie
Published: November 2012

Motivation:  In silico methods provide efficient ways to predict possible interactions between drugs and targets. Supervised learning approach, bipartite local model (BLM), has recently been shown to be effective in prediction of drug–target interactions. However, for drug-candidate compounds or target-candidate proteins that currently have no known interactions available, its pure ‘local’ model is not able to be learned and hence BLM may fail to make correct prediction when involving such kind of new candidates.

Results: We present a simple procedure called neighbor-based interaction-profile inferring (NII) and integrate it into the existing BLM method to handle the new candidate problem. Specifically, the inferred interaction profile is treated as label information and is used for model learning of new candidates. This functionality is particularly important in practice to find targets for new drug-candidate compounds and identify targeting drugs for new target-candidate proteins. Consistent good performance of the new BLM–NII approach has been observed in the experiment for the prediction of interactions between drugs and four categories of target proteins. Especially for nuclear receptors, BLM–NII achieves the most significant improvement as this dataset contains many drugs/targets with no interactions in the cross-validation. This demonstrates the effectiveness of the NII strategy and also shows the great potential of BLM–NII for prediction of compound–protein interactions.

Contact:  jpmei@ntu.edu.sg

Supplementary information:  Supplementary data are available at Bioinformatics online.
DoseSim: a tool for pharmacokinetic/pharmacodynamic analysis and dose reconstruction
Authors: Reisfeld Brad , Ivy Jaime H. , Lyons Michael A. , Wright Jesse M. , Rogers Justin L. , Mayeno Arthur N.
Published: November 2012

Summary: Assessing and improving the safety of chemicals and the efficacy of drugs depends on an understanding of the biodistribution, clearance and biological effects of the chemical(s) of interest. A promising methodology for the prediction of these phenomena is physiologically based pharmacokinetic/pharmacodynamic modeling, which centers on the prediction of chemical absorption, distribution, metabolism and excretion (pharmacokinetics) and the biological effects (pharmacodynamics) of the chemical on the organism. Strengths of this methodology include modeling across multiple scales of biological organization and facilitate the extrapolation of results across routes of exposure, dosing levels and species. It is also useful as the foundation for tools to (i) predict biomarker levels (concentrations of chemical species found in the body that indicate exposure to a foreign chemical), given a chemical dose or exposure; (ii) reconstruct a dose, given the levels of relevant biomarkers; and (iii) estimate population variability. Despite the importance and promise of physiologically based pharmacokinetic /pharmacodynamics-based approaches to forward and reverse dosimetry, there is currently a lack of user-friendly, freely available implementations that are accessible and useful to a broad range of users. DoseSim was developed to begin to fill this gap.

Availability: The application is available under the GNU General Public License from http://scb.colostate.edu/dosesim.html.

Contact:  brad.reisfeld@colostate.edu
mzMatch–ISO: an R tool for the annotation and relative quantification of isotope-labelled mass spectrometry data
Authors: Chokkathukalam Achuthanunni , Jankevics Andris , Creek Darren J. , Achcar Fiona , Barrett Michael P. , Breitling Rainer
Published: November 2012

Motivation: Stable isotope-labelling experiments have recently gained increasing popularity in metabolomics studies, providing unique insights into the dynamics of metabolic fluxes, beyond the steady-state information gathered by routine mass spectrometry. However, most liquid chromatography–mass spectrometry data analysis software lacks features that enable automated annotation and relative quantification of labelled metabolite peaks. Here, we describe mzMatch–ISO, a new extension to the metabolomics analysis pipeline mzMatch.R.

Results: Targeted and untargeted isotope profiling using mzMatch–ISO provides a convenient visual summary of the quality and quantity of labelling for every metabolite through four types of diagnostic plots that show (i) the chromatograms of the isotope peaks of each compound in each sample group; (ii) the ratio of mono-isotopic and labelled peaks indicating the fraction of labelling; (iii) the average peak area of mono-isotopic and labelled peaks in each sample group; and (iv) the trend in the relative amount of labelling in a predetermined isotopomer. To aid further statistical analyses, the values used for generating these plots are also provided as a tab-delimited file. We demonstrate the power and versatility of mzMatch–ISO by analysing a 13C-labelled metabolome dataset from trypanosomal parasites.

Availability: mzMatch.R and mzMatch–ISO are available free of charge from http://mzmatch.sourceforge.net and can be used on Linux and Windows platforms running the latest version of R.

Contact:  rainer.breitling@manchester.ac.uk  .

Supplementary information:  Supplementary data are available at Bioinformatics online
PASS-bis: a bisulfite aligner suitable for whole methylome analysis of Illumina and SOLiD reads
Authors: Campagna Davide , Telatin Andrea , Forcato Claudio , Vitulo Nicola , Valle Giorgio
Published: November 2012

Summary: The sequencing of bisulfite-treated DNA (Bi-Seq) is becoming a gold standard for methylation studies. The mapping of Bi-Seq reads is complex and requires special alignment algorithms. This problem is particularly relevant for SOLiD color space, where the bisulfite conversion C/T changes two adjacent colors into 16 possible combinations. Here, we present an algorithm that efficiently aligns Bi-Seq reads obtained either from SOLiD or Illumina. An accompanying methylation-caller program creates a genomic view of methylated and unmethylated Cs on both DNA strands.

Availability and implementation: The algorithm has been implemented as an option of the program PASS, freely available at http://pass.cribi.unipd.it.

Contact:  pass@cribi.unipd.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Age determination of Atlantic halibut (Hippoglossus hippoglossus L.) along the coast of Norway: status and improvements
Authors: Karlson Stine , Michalsen Kathrine , Folkvord Arild
Published: November 2012

Karlson, S., Michalsen, K., and Folkvord, A. 2013. Age determination of Atlantic halibut (Hippoglossus hippoglossus L.) along the coast of Norway: status and improvements. – ICES Journal of Marine Science, 70:50–55. This study re-evaluates the current ageing methodology for the Atlantic halibut, Hippoglossus hippoglossus. The traditional method is through surface readings of otoliths, but, based on new experiments with different preparation treatments and techniques, a more accurate and cost-efficient procedure for the age determination of Atlantic halibut is proposed.
Prognostic Significance of Blood Lactate and Lactate Clearance in Trauma Patients
Authors: Régnier Marie-Alix , Raux Mathieu , Le Manach Yannick , Asencio Yves , Gaillard Johann , Devilliers Catherine , Langeron Olivier , Riou Bruno
Published: November 2012

Background

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined.

Methods

Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method.

Results

The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate.

Conclusions

Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.
Asymmetric Facet Joint Osteoarthritis and Its Relationships to Facet Orientation, Facet Tropism, and Ligamentum Flavum Thickening
Authors: Liu Hai-xiao , Shen Yue , Shang Ping , Ma Yan-xu , Cheng Xiao-jie , Xu Hua-zi
Published: November 2012

Study Design:

The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography among elderly patients with low back or leg pain.

Objective:

To reveal the phenomenon of asymmetry regarding facet joint osteoarthritis (FJOA) in old patients and establish its relationships to spinal level, facet orientation, facet tropism and ligamentum flavum (LF) thickening.

Summary of Background Data:

There were few reports regarding left-right asymmetry among severity of FJOA and its relationships to spinal level, facet orientation, facet tropism, and LF thickening remained unclear.

Methods:

The grade of bilateral FJOA was evaluated using 4-grade scale on computerized tomography images at the L3–4, L4–5, and L5–S1 levels of patients with age ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric FJOA group (FJOA I–II on both sides or FJOA III–IV on both sides) and asymmetric FJOA group (FJOA I–II on one side and FJOA III–IV on the other side). The relationships of FJOA to spinal level, facet orientation, facet tropism, and LF hypertrophy were evaluated.

Results:

No association between asymmetric FJOA and spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference in facet orientation between 2 sides was observed at the L4–5 (P=0.018) and L5–S1 levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed significant difference in prevalence of facet tropism at the L5–S1 level (P<0.001). The LF showed significantly thicker on the side of FJOA III–IV than the side of FJOA I–II at each level in asymmetric FJOA group (P<0.05). However, no difference was found in thickness between 2 sides in symmetric FJOA group (P>0.05).

Conclusions:

Asymmetric FJOA is associated with facet orientation and tropism, but not with spinal level. There is a close relationship between severity of FJOA and LF thickness.
Hybrid Decompression and Fixation Technique Versus Plated 3-Vertebra Corpectomy for 4-Segment Cervical Myelopathy
Authors: Odate Seiichi , Shikata Jitsuhiko , Kimura Hiroaki , Soeda Tsunemitsu
Published: November 2012

Study Design:

A retrospective comparative study.

Objective:

The purpose of this study was to compare the stability and outcomes of a hybrid technique with those of a 3-vertebra corpectomy in the management of 4-segment cervical myelopathy.

Summary of Background Data:

Patients with primarily ventral disease and loss of cervical lordosis are considered good candidates for anterior surgery. Cervical corpectomy is commonly performed in patients with multilevel cervical myelopathy. Corpectomies including >3 vertebraes entail an extremely high risk of reconstruction failure. To avoid the need to perform a 3-vertebra corpectomy, we use a hybrid decompression and fixation technique. This hybrid technique is a technique to obtain optimum decompression and fixation in patients with multilevel cervical myelopathy.

Methods:

A total of 81 patients with multilevel cervical myelopathy who underwent 4-segment cervical fixation with a minimum 2-year follow-up were included.

Results:

The hybrid technique involved combining a plated 2-vertebra corpectomy and single-level discectomy with stand-alone cage fixation. This technique was performed in 39 patients, and the plated 3-vertebra corpectomy was performed in 42 patients. Nine patients (21%) who underwent the plated 3-vertebra corpectomy were treated with halo immobilization, but no patient in the hybrid group required this treatment (P=0.002). There were fewer instances of reconstruction failure in the hybrid group than in the 3-vertebra corpectomy group (0% vs. 10%, respectively; P=0.048) and fewer instances of C5 palsy (3% vs. 17%, respectively; P <0.0001). The incidence of postoperative C5 palsy was 25% for C3–C5 corpectomy, 19% for C4–C6 corpectomy, and 11% for C4–C5 corpectomy+C6–C7 discectomy.

Conclusions:

The hybrid technique has the following advantages over 3-vertebra corpectomy for 4-segment cervical fixation: a shorter graft bone and plate are required; the fixed segment has greater initial stability; postoperative external immobilization is simplified; and the risk of reconstruction failure and postoperative C5 palsy is reduced markedly.
Two-Year Evaluation of the X-STOP Interspinous Spacer in Different Primary Patient Populations With Neurogenic Intermittent Claudication Because of Lumbar Spinal Stenosis
Authors: Hartjen Charles A. , Resnick Daniel K. , Hsu Ken Y. , Zucherman James F. , Hsu Emily H. , Skidmore Grant A.
Published: November 2012

Study Design:

Multicenter, prospective single-arm study in patients diagnosed with neurogenic intermittent claudication because of lumbar spinal stenosis.

Objective:

To collect data from 2 different primary patient populations, new participants meeting entry criteria [Continued Access Program (CAP)], or subjects who had been randomly assigned to nonsurgical management in the pivotal Investigational Device Exemption study and failed to respond upon study completion [Crossover Study (COS)].

Summary of Background Data:

The X-STOP interspinous spacer is a minimally invasive treatment option for neurogenic intermittent claudication shown to improve pain, physical functioning, and/or overall quality of life.

Methods:

Fifty-five subjects were enrolled, 42 in CAP and 13 in COS. Zurich Claudication Questionnaire (ZCQ) success rates were obtained based on the number of subjects achieving a threshold level of success. Mean SF-36 domain scores were compared with baseline using repeated measures analysis of variance.

Results:

Eighty percent of subjects completed the study. At 2 years, 26/43 subjects (60.5%) achieved clinically significant improvement in the Symptom Severity domain, 25/43 (58.1%) achieved clinically significant improvement in the Physical Function domain, and 31/44 (70.5%) achieved clinically significant improvement in the Patient Satisfaction domain of the ZCQ. Statistically significant improvement in mean scores was obtained in all physical domains of the SF-36 (with the exception of General Health) at 24 months. Mean improvement in ZCQ and SF-36 scores was not as pronounced in the COS cohort compared with the CAP cohort. The most frequently reported device-related or treatment-related adverse event was stenosis pain reported by 3 subjects.

Conclusions:

Overall data are consistent with the randomized pivotal Investigational Device Exemption trial. On the basis of the COS cohort which was subject to several additional years of failed conservative treatment, overall success rates do not improve as greatly in patients with long-standing lumbar spinal stenosis symptoms.
Camptocormia Due to Inclusion Body Myositis
Authors: Goodman Brent P. , Liewluck Teerin , Crum Brian A. , Spinner Robert J.
Published: November 2012

Inclusion body myositis is the most common idiopathic inflammatory myopathy in elderly individuals. It typically causes proximal and distal limb weakness with forearm flexors and quadriceps being the most severely affected muscles. Axial musculature is infrequently involved. Here, we report an 80-year-old man who presented with an 18-month history of progressive truncal weakness causing stooped posture while standing and walking. Neurologic examination revealed no limb weakness. magnetic resonance imaging studies showed atrophy and findings, suggesting fatty replacement of paraspinal muscles. Needle electromyography confirmed the presence of an axial myopathy. Thoracic paraspinal muscle biopsy showed canonical features of inclusion body myositis. The current patient broadens the clinical presentation of inclusion body myositis.
Virologic Responses to Add‐on Adefovir Dipivoxil Treatment Versus Entecavir Monotherapy in Children With Lamivudine‐resistant Chronic Hepatitis B
Authors: Chu MiAe , Cho Seung Man , Choe Byung‐Ho , Cho Min Hyun , Kwon Soonhak , Lee Won Kee
Published: November 2012

Purpose:

The aim of the study was to compare the virologic response to adefovir (ADV) add‐on therapy with switching to entecavir (ETV) monotherapy in children and adolescents with chronic hepatitis B (CHB) who have developed lamivudine (LAM) resistance during LAM treatment.

Methods:

Twenty‐seven consecutive patients with CHB who had developed LAM resistance during LAM treatment were included. Of these 27 patients, 8 patients were treated with the addition of ADV to ongoing LAM and 8 patients were treated by switching to ETV monotherapy and each of these 16 patients were compared with the 11 patients who were treated by switching to ADV alone, as a historical control. Therapeutic responses to treatment were evaluated at 12, 24, 36, and 48 weeks from the initiation of therapy by measuring the decrement of hepatitis B virus (HBV)‐DNA titers.

Results:

The therapeutic period for HBV‐DNA titer decrement (>2 log10 IU/mL) was significantly shorter in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.008); however, there was no significant difference between the LAM+ADV group and the ETV group. The rate of virologic response, defined as decrement in HBV‐DNA titer to undetectable levels at 24 weeks, was significantly higher in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.029).

Conclusions:

Both the LAM+ADV combination therapy and ETV monotherapy exhibited significantly more effective virologic responses compared to the ADV monotherapy in children and adolescents with LAM‐resistant CHB, although there was no significant difference between the LAM+ADV group and the ETV group.
Improved Outcomes With Quality Improvement Interventions in Pediatric Inflammatory Bowel Disease
Authors: Samson Charles M. , Morgan Pamela , Williams Elizabeth , Beck Lee , Addie‐Carson RicJunette , McIntire Stacy , Booth Andrea , Mendez Eduardo , Luzader Carolyn , Tomer Gitit , Saeed Shehzad , Donovan Edward , Bucuvalas John , Denson Lee A.
Published: November 2012

Objectives:

Variations in chronic illness care are common in our health care system and may lead to suboptimal outcomes. Specifically, inconsistent use and suboptimal medication dosing have been demonstrated in the care of patients with inflammatory bowel disease (IBD). Quality improvement (QI) efforts have improved outcomes in conditions such as asthma and diabetes mellitus, but have not been well studied in IBD. We hypothesized that QI efforts would lead to improved outcomes in our pediatric IBD population.

Methods:

A QI team was formed within our IBD center in 2005. By 2007, we began prospectively capturing physician global assessment (PGA) and patient‐reported global assessment. Significant QI interventions included creating evidence‐based medication guidelines, joining a national QI collaborative, initiation of preclinic planning, and monitoring serum 25‐hydroxyvitamin D.

Results:

From 2007 to 2010, 505 patients have been followed at our IBD center. During this time, the frequency of patients in clinical remission increased from 59% to 76% (P < 0.05), the frequency of patients who report that their global assessment is >7 increased from 69% to 80% (P < 0.05), and the frequency of patients with a Short Pediatric Crohn's Disease Activity Index (sPCDAI) <15 increased from 60% to 77% (P < 0.05). The frequency of repeat steroid use decreased from 17% to 10% (P < 0.05). We observed an association between the use of a vitamin D supplement (P = 0.02), serum 25‐hydroxyvitamin D (P < 0.05), and quiescent disease activity.

Conclusions:

Our results show that significant improvements in patient outcomes are associated with QI efforts that do not rely on new medication or therapies.
Intestinal Smooth Muscle Dysfunction Develops Postnatally in Cystic Fibrosis Mice
Authors: De Lisle Robert C. , Meldi Lauren , Mueller Racquel
Published: November 2012

Objectives:

Intestinal dysmotility is one of the effects of cystic fibrosis (CF), but when and how this develops is not well understood. The goal of the present study was to use the Cftr knockout mouse to determine when in development circular smooth muscle of the small intestine becomes dysfunctional.

Methods:

Wild‐type (WT) and CF mice were used at postnatal day 5 (P5) through adult. Pieces of small intestine were used to measure contractile activity of the circular muscle. Bacterial overgrowth was measured by quantitative polymerase chain reaction (PCR) of the bacterial 16S gene. Intestinal gene expression was determined by quantitative reverse transcription polymerase chain reaction (RT‐PCR). Prostaglandin E2 (PGE2) and its metabolites were measured by enzyme immunoassay.

Results:

CF circular muscle response to cholinergic stimulation was similar to WT at P5, became somewhat impaired at P7, and was severely impaired by P14. In the CF intestine, bacterial overgrowth occurred by P4 and was maintained into adulthood. Eicosanoid metabolic gene expression in the CF intestine did not differ from WT shortly after birth. The phospholipase A2 genes, Pla2g4c and Pla2g5 exhibited increased expression in CF mice at P24. Prostaglandin degradative genes, Hpgd and Ptgr1, showed lower expression in CF as compared with WT at P16 and P24, respectively. PGE2 levels were significantly greater in CF mice at most ages from P7 through adulthood.

Conclusions:

The results clearly demonstrate that lack of CFTR itself does not cause smooth muscle dysfunction, because the circular muscle from P5 CF mice had normal activity and dysfunction developed between P7 and P14.
Effect of the Exposure to TV Food Advertisements on the Consumption of Foods by Mothers and Children
Authors: Díaz‐Ramírez Glenda , Jiménez‐Cruz Arturo , Souto‐Gallardo Maria de las Cruces , Bacardí‐Gascón Montserrat
Published: November 2012

Foods advertised were recorded in 2 television (TV) channels. The present article studies the association between products advertised and those consumed by mothers and children. A total of 365 mothers and their children were assessed. A positive correlation was observed between the food advertisements that the mothers recalled and the frequency of TV food advertisements (Rho = 0.44, P = 0.03). A positive correlation was found between the frequency of the foods advertised on TV and the consumption of these by the mothers (r = 0.73, P = 0.0001) and their children (Rho = 0.66, P = 0.0001). These results suggest that TV advertisements influence the food choices of mothers and children.
Milk Temperature Influences Esophageal Motility in the Newborn Lamb
Authors: Djeddi Djamal , Samson Nathalie , Praud Jean‐Paul
Published: November 2012

Esophageal dysmotility is common in infants. We aimed to evaluate the influence of milk temperature on esophageal motility using multichannel intraluminal impedance‐pH monitoring (MII‐pH). Five healthy lambs, ages 2 to 3 days, underwent a MII‐pH whereas bottle‐fed randomly with 50 mL of ewe milk at 26°C, 38.5°C, and 41.5°C. Impedance motility parameters were studied on 5 swallows at each temperature. At 38.5°C we noted a higher total propagation velocity and a shorter total bolus transit time (TBTT) (P < 0.05). These unique results suggest a potential role of milk temperature alterations in improving oral feeding in infants with esophageal dysmotility.
TGF‐β Affects Enterocyte Turnover in Correlation With TGF‐β Receptor Expression After Massive Small Bowel Resection
Authors: Sukhotnik Igor , Lulu Shani Ben , Pollak Yulia , Bejar Jacob , Coran Arnold G. , Mogilner Jorge G.
Published: November 2012

Objectives:

In the present study, we evaluated the effect of transforming growth factor‐beta 2 (TGF‐β2)‐enriched diet on enterocyte turnover and correlated it with TGF‐β2 receptor expression along the villus–crypt axis in a rat model of short bowel syndrome (SBS).

Methods:

CaCo‐2 cells were incubated with increasing concentrations of TGF‐β2. Alamar Blue reduction test was used for investigation of cell viability and evaluation of cell apoptosis was assessed by flow cytometry. Male rats were divided into 4 groups: Sham rats underwent bowel transection, Sham TGF‐β rats were treated with diet enriched with TGF‐β2, SBS rats underwent a 75% bowel resection, and SBS TGF‐β rats were fed a diet enriched with TGF‐β2 after bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. TGF‐β2r expression in villus tips, lateral villi and crypts was assessed by immunohistochemistry. The effect of TGF‐β2 on enterocyte turnover for each compartment was evaluated in correlation with TGF‐β2r expression.

Results:

Incubation of CaCo‐2 cells with TGF‐β2 resulted in a significant decrease in cell viability and increased cell apoptosis. TGF‐β2r expression in crypts increased in SBS rats (vs sham) and was accompanied by decreased cell proliferation and increased cell apoptosis following TGF‐β2 administration. A significant decrease in TGF‐β2r expression at villous tips in SBS rats was accompanied by a decreased cell apoptosis in this compartment following exposure to TGF‐β2‐enriched diet.

Conclusions:

In a rat model of SBS, the inhibiting effect of TGF‐β2 on enterocyte turnover correlates with TGF‐β2 receptor expression along the villus–crypt axis.
Autosomal Dominant Ménétrier‐like Disease
Authors: Strisciuglio Caterina , Corleto Vito D. , Brunetti‐Pierri Nicola , Piccolo Pasquale , Sangermano Riccardo , Rindi Guido , Martini Maurizio , D'Armiento Francesco P. , Staiano Annamaria , Miele Erasmo
Published: November 2012

Background:

Familial occurrence of Ménétrier disease is rare and has been reported only in few instances.

Methods:

Affected patients from a large pedigree were evaluated at the clinical, endoscopic, and pathological levels.

Results:

Affected members presented with gastropathy of variable severity but without protein loss. Endoscopy and pathology findings were consistent with Ménétrier disease; however, gastric transforming growth factor α (TGF‐α) immunohistochemistry and real‐time polymerase chain reaction showed no increase in TGF‐α expression.

Conclusions:

We describe a unique, 4‐generation pedigree with autosomal dominant gastropathy exhibiting the typical clinical, endoscopic, and pathological findings of Ménétrier‐like disease, though in the absence of protein loss and with no increase in the levels of gastric TGF‐α. Members of this family may be affected by a novel and previously unrecognised hereditary form of gastric hyperplasia.
Parental Report of Abdominal Pain and Abdominal Pain–related Functional Gastrointestinal Disorders From a Community Survey
Authors: Saps Miguel , Adams Papa , Bonilla Silvana , Chogle Ashish , Nichols‐Vinueza Diana
Published: November 2012

Background and Aims:

Functional gastrointestinal disorders (FGIDs) are common in children. Abdominal pain (AP) is the most common gastrointestinal (GI) symptom in children. The severity of AP drives medical consultations and quality of life in adult patients with irritable bowel syndrome (IBS). Thirty‐eight percent of 8‐ to 15‐year‐old schoolchildren report AP weekly with 24% of those children reporting persistence of AP >8 weeks. Despite the high prevalence of AP, only 2% of school children seek medical attention for AP. Lack of parental knowledge on their child's symptoms may constitute one of the factors affecting the low ratio of consultation in children reporting AP. The aim was to assess parental reports of AP symptoms in a population of healthy community children.

Methods:

Data of 5 studies with identical methodology to assess GI symptoms in children with celiac disease (CD), cow's milk allergy (CMA), pyloric stenosis (PS), Henoch‐Schönlein purpura (HSP), and stem cell transplant (SC) and their healthy siblings were reviewed: a phone questionnaire on GI symptoms and Pediatric Gastrointestinal Symptoms Rome III version questionnaire (QPGS‐RIII). Inclusion criteria were healthy children 4 to 18 years of age with a sibling previously diagnosed with CD, CMA, PS, HSP, or SC.

Results:

Data on 246 healthy children, mean age (9.8 years, range 3–24, 112 girls) were obtained. Parents reported presence of AP in the last 8 weeks before the telephone contact in 20 (8.1%) children (age range 4–18 years, 11 girls). There was no significant difference in AP prevalence between boys and girls (P = 0.64). Six children (2.4%) met QPGS‐RIII diagnostic criteria for FGIDs: 3 functional abdominal pain (FAP) and 3 IBS.

Conclusions:

AP was common in community children. FAP was the most common FGID among healthy community children. The prevalence of AP by parental report is lower than the previously published prevalence of AP reported by children. Lack of awareness of children's symptoms may play a role in the low ratio of consultation for AP in symptomatic children. Future prospective studies should confirm our findings and investigate the factors influencing the medical consultation decision including parental awareness of children's symptoms.
Obesity After Pediatric Liver Transplantation
Authors: Sundaram Shikha S. , Alonso Estella M. , Zeitler Phil , Yin Wanron , Anand Ravinder ,   SPLIT Research Group
Published: November 2012

Objectives:

Pediatric obesity has become a significant public health concern. The historical focus in pediatric liver transplant (LT) has been undernutrition, with limited knowledge regarding obesity. Therefore, we sought to determine the prevalence of obesity in pediatric LT, compare it to National Health and Nutrition Examination Surveys (NHANES) data, and identify risk factors for obesity in pediatric LT.

Methods:

SPLIT, which collects pediatric LT data at 39 centers, was queried for subjects ages 2 to 18 years at follow‐up, LT between 1995 and 2007, and with at least 1 body mass index measured 1 to 5 years after LT.

Results:

Of 1706 individuals included, 44% had biliary atresia (47% boys, 58% white, mean age at LT 4.6 years). Of these individuals, 19% were obese at 1 year and 18% at 3 years, higher than in the general pediatric population reported by 2003–2004 NHANES, whereas 11% obesity at 5 years after LT was similar to NHANES data. Using logistic regression, Hispanic ethnicity (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.19–2.23), steroid use at follow‐up (OR 1.48, 95% CI 1.23–1.77), overweight (OR 4.34, 95% CI 2.91–6.68), and obesity (OR 10.62, 95% CI 5.9–19.65) at LT independently predicted post‐LT obesity.

Conclusions:

These findings suggest a need to broaden standard care to include obesity assessment and intervention in routine pre‐ and posttransplant care.
Endoscopic and Histological Gastric Lesions in Children With Celiac Disease
Authors: Nenna Raffaella , Magliocca Fabio Massimo , Tiberti Claudio , Mastrogiorgio Gerarda , Petrarca Laura , Mennini Maurizio , Lucantoni Federica , Luparia Rita Pia Lara , Bonamico Margherita
Published: November 2012

Objectives:

Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC).

Methods:

In a retrospective study on 226 patients with CD (82 M; median age: 5.7years) at diagnosis and 154 GC (66 M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti‐gastric parietal cell antibodies (GPCA) were assayed by enzyme‐linked immunosorbent assay.

Results:

A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) children with GC (91.7% had CSG). Among patients with CSG, Hp infection was more frequent in controls than in celiac children (P < 0.0001). Ten of 90 patients with CD and 1 of 29 controls were positive for GPCA.

Conclusions:

Gastritis is a common finding in children with CD and adolescents. In celiac subjects, CSG is the most frequently detected. Our data suggest the hypothesis that LG may be related to a longer exposure to gluten. The presence of GPCA may suggest the presence of an underlying autoimmune process.