bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?
Authors: Tolo Isaiah , Thomas Jonathan C. , Fischer Rebecca S. B. , Brown Eric L. , Gray Barry M. , Robinson D. Ashley
Published: April 2016

Staphylococcus epidermidis
is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of
S. epidermidis
distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between
fdh
-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (
icaA
, IS
256
,
sesD
[
bhp
],
mecA
, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital.
Cell-Free Hepatitis B Virus Capsid Assembly Dependent on the Core Protein C-Terminal Domain and Regulated by Phosphorylation
Authors: Ludgate Laurie , Liu Kuancheng , Luckenbaugh Laurie , Streck Nicholas , Eng Stacey , Voitenleitner Christian , Delaney William E. , Hu Jianming
Published: April 2016

Multiple subunits of the hepatitis B virus (HBV) core protein (HBc) assemble into an icosahedral capsid that packages the viral pregenomic RNA (pgRNA). The N-terminal domain (NTD) of HBc is sufficient for capsid assembly, in the absence of pgRNA or any other viral or host factors, under conditions of high HBc and/or salt concentrations. The C-terminal domain (CTD) is deemed dispensable for capsid assembly although it is essential for pgRNA packaging. We report here that HBc expressed in a mammalian cell lysate, rabbit reticulocyte lysate (RRL), was able to assemble into capsids when (low-nanomolar) HBc concentrations mimicked those achieved under conditions of viral replication
in vivo
and were far below those used previously for capsid assembly
in vitro
. Furthermore, at physiologically low HBc concentrations in RRL, the NTD was insufficient for capsid assembly and the CTD was also required. The CTD likely facilitated assembly under these conditions via RNA binding and protein-protein interactions. Moreover, the CTD underwent phosphorylation and dephosphorylation events in RRL similar to those seen
in vivo
which regulated capsid assembly. Importantly, the NTD alone also failed to accumulate in mammalian cells, likely resulting from its failure to assemble efficiently. Coexpression of the full-length HBc rescued NTD assembly in RRL as well as NTD expression and assembly in mammalian cells, resulting in the formation of mosaic capsids containing both full-length HBc and the NTD. These results have important implications for HBV assembly during replication and provide a facile cell-free system to study capsid assembly under physiologically relevant conditions, including its modulation by host factors.

IMPORTANCE
Hepatitis B virus (HBV) is an important global human pathogen and the main cause of liver cancer worldwide. An essential component of HBV is the spherical capsid composed of multiple copies of a single protein, the core protein (HBc). We have developed a mammalian cell-free system in which HBc is expressed at physiological (low) concentrations and assembles into capsids under near-physiological conditions. In this cell-free system, as in mammalian cells, capsid assembly depends on the C-terminal domain (CTD) of HBc, in contrast to other assembly systems in which HBc assembles into capsids independently of the CTD under conditions of nonphysiological protein and salt concentrations. Furthermore, the phosphorylation state of the CTD regulates capsid assembly and RNA encapsidation in the cell-free system in a manner similar to that seen in mammalian cells. This system will facilitate detailed studies on capsid assembly and RNA encapsidation under physiological conditions and identification of antiviral agents that target HBc.
Dynamic Nucleolar Targeting of Dengue Virus Polymerase NS5 in Response to Extracellular pH
Authors: Fraser Johanna E. , Rawlinson Stephen M. , Heaton Steven M. , Jans David A.
Published: April 2016

The nucleolar subcompartment of the nucleus is increasingly recognized as an important target of RNA viruses. Here we document for the first time the ability of dengue virus (DENV) polymerase, nonstructural protein 5 (NS5), to accumulate within the nucleolus of infected cells and to target green fluorescent protein (GFP) to the nucleolus of live transfected cells. Intriguingly, NS5 exchange between the nucleus and nucleolus is dynamically modulated by extracellular pH, responding rapidly and reversibly to pH change, in contrast to GFP alone or other nucleolar and non-nucleolar targeted protein controls. The minimal pH-sensitive nucleolar targeting region (pHNTR), sufficient to target GFP to the nucleolus in a pH-sensitive fashion, was mapped to NS5 residues 1 to 244, with mutation of key hydrophobic residues, Leu-165, Leu-167, and Val-168, abolishing pHNTR function in NS5-transfected cells, and severely attenuating DENV growth in infected cells. This is the first report of a viral protein whose nucleolar targeting ability is rapidly modulated by extracellular stimuli, suggesting that DENV has the ability to detect and respond dynamically to the extracellular environment.

IMPORTANCE
Infections by dengue virus (DENV) threaten 40% of the world's population yet there is no approved vaccine or antiviral therapeutic to treat infections. Understanding the molecular details that govern effective viral replication is key for the development of novel antiviral strategies. Here, we describe for the first time dynamic trafficking of DENV nonstructural protein 5 (NS5) to the subnuclear compartment, the nucleolus. We demonstrate that NS5's targeting to the nucleolus occurs in response to acidic pH, identify the key amino acid residues within NS5 that are responsible, and demonstrate that their mutation severely impairs production of infectious DENV. Overall, this study identifies a unique subcellular trafficking event and suggests that DENV is able to detect and respond dynamically to environmental changes.
Assembly of Lipoic Acid on Its Cognate Enzymes: an Extraordinary and Essential Biosynthetic Pathway
Authors: Cronan John E.
Published: April 2016

Although the structure of lipoic acid and its role in bacterial metabolism were clear over 50 years ago, it is only in the past decade that the pathways of biosynthesis of this universally conserved cofactor have become understood. Unlike most cofactors, lipoic acid must be covalently bound to its cognate enzyme proteins (the 2-oxoacid dehydrogenases and the glycine cleavage system) in order to function in central metabolism. Indeed, the cofactor is assembled on its cognate proteins rather than being assembled and subsequently attached as in the typical pathway, like that of biotin attachment. The first lipoate biosynthetic pathway determined was that of
Escherichia coli
, which utilizes two enzymes to form the active lipoylated protein from a fatty acid biosynthetic intermediate. Recently, a more complex pathway requiring four proteins was discovered in
Bacillus subtilis
, which is probably an evolutionary relic. This pathway requires the H protein of the glycine cleavage system of single-carbon metabolism to form active (lipoyl) 2-oxoacid dehydrogenases. The bacterial pathways inform the lipoate pathways of eukaryotic organisms. Plants use the
E. coli
pathway, whereas mammals and fungi probably use the
B. subtilis
pathway. The lipoate metabolism enzymes (except those of sulfur insertion) are members of PFAM family PF03099 (the cofactor transferase family). Although these enzymes share some sequence similarity, they catalyze three markedly distinct enzyme reactions, making the usual assignment of function based on alignments prone to frequent mistaken annotations. This state of affairs has possibly clouded the interpretation of one of the disorders of human lipoate metabolism.
Motorcycle racer with unilateral forearm flexor and extensor chronic exertional compartment syndrome
Authors: Winkes Michiel B , Teijink Joep A , Scheltinga Marc R
Published: April 2016

We discuss a case of a 26-year-old man, a motorcycle racer, who presented with progressive pain, weakness and swelling of his right forearm and loss of power in his index finger, experienced during motor racing. Chronic exertional compartment syndrome (CECS) of both flexor and extensor compartments of his forearm was diagnosed by dynamic intracompartmental muscle pressure measurements. After fasciotomies, all symptoms were resolved and the patient was able to improve on his preinjury racing skills, without any limitations. A literature review and a surgical ‘how-to’ for correct release of the extensor and deep flexor compartments of the forearm are provided.
Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: a mixed studies systematic review
Authors: Forsdyke Dale , Smith Andy , Jones Michelle , Gledhill Adam
Published: April 2016

Background

The prime focus of research on sports injury has been on physical factors. This is despite our understanding that when an athlete sustains an injury it has psychosocial as well as physical impacts. Psychosocial factors have been suggested as prognostic influences on the outcomes of rehabilitation. The aim of this work was to address the question: are psychosocial factors associated with sports injury rehabilitation outcomes in competitive athletes?

Study design

Mixed studies systematic review (PROSPERO reg.CRD42014008667).

Method

Electronic database and bibliographic searching was undertaken from the earliest entry until 1 June 2015. Studies that included injured competitive athletes, psychosocial factors and a sports injury rehabilitation outcome were reviewed by the authors. A quality appraisal of the studies was undertaken to establish the risk of reporting bias.

Results

25 studies were evaluated that included 942 injured competitive athletes were appraised and synthesised. Twenty studies had not been included in previous reviews. The mean methodological quality of the studies was 59% (moderate risk of reporting bias). Convergent thematic analysis uncovered three core themes across the studies: (1) emotion associated with rehabilitation outcomes; (2) cognitions associated with rehabilitation outcomes; and (3) behaviours associated with rehabilitation outcomes. Injury and performance-related fears, anxiety and confidence were associated with rehabilitation outcomes. There is gender-related, age-related and injury-related bias in the reviewed literature.

Conclusions

Psychosocial factors were associated with a range of sports injury rehabilitation outcomes. Practitioners need to recognise that an injured athlete's thoughts, feelings and actions may influence the outcome of rehabilitation.
Availability and provision of emergency obstetric care under a public–private partnership in three districts of Gujarat, India: lessons for Universal Health Coverage
Authors: Iyer V , Sidney K , Mehta R , Mavalankar D
Published: April 2016

Objective

The state of Gujarat in India (population 60 million) has implemented a public–private partnership (PPP) with private obstetricians called the Chiranjeevi Yojana (CY) since 2006. This study investigated the adequacy of basic and comprehensive emergency obstetric care (BEmOC and CEmOC) services through the public and private sectors with reference to the United Nations (UN) guidelines.

Design

A cross-sectional facility survey was conducted in three districts.

Results

A total of 300 facilities, 151 public and 149 private, had provided obstetric services to a total of 53 896 births in the past 6 months. Nearly half, 135 facilities (104 public and 31 private), individually reported <10 births per month (low load), and, as a group, reported only 4% of all births in the past 6 months. The remaining 165 high-load facilities consisted of 23 (3 public; 20 private) full CEmOC, 66 (1; 65) ‘potential’ CEmOC, 12 (3; 9) BEmOC and 57 (40; 17) non-EmOC facilities. All the three districts exceeded the UN recommendation for EmOC availability by 3.3 to 11.3 times. Free provision, through both public and PPP facilities, ranged from 1.42 to 3.43. The actual performance was nearly double the recommendation for CEmOC but inadequate for BEmOC.

Conclusions

Public sector EmOC availability and provision is negligible. Private sector availability is well beyond the recommended UN norms. The CY programme has resulted in increased availability and provision of EmOC services. However, the overall provision of EmOC is compromised due to the poor performance of BEmOC functions and clustering of private facilities in towns.
Republished: Basilar artery occlusion in a child treated successfully with mechanical thrombectomy using ADAPT
Authors: Lena Jonathan , Eskandari Ramin , Infinger Libby , Fargen Kyle M , Spiotta Alejandro , Turk Aquilla , Turner Raymond D , Chaudry Imran
Published: April 2016

Acute ischemic stroke (AIS) in the pediatric population is rare. Furthermore, it is common for physicians to take significantly longer diagnosing a posterior circulation stroke in a child than in an adult. There are increasing case reports in the literature of treating AIS in children with intravenous tissue plasminogen activator, intra-arterial thrombolysis, and/or mechanical thrombectomy. We present the first case of pediatric AIS treated using a direct aspiration first pass technique (ADAPT) as a means of mechanical thrombectomy.
Spontaneous decay in cold dense atomic systems: caloric effect and spectrum of emitted light
Authors: Prepelita Oleg
Published: April 2016

We discuss collision-induced spontaneous decay in a system of cold atoms and caloric effect manifesting in the heating of the atomic system during spontaneous decay. It is shown that the caloric effect is caused by inelastic atom–atom collisions accompanied by the spontaneous emission of photons. Because of the imbalance between the rate of emission of the photons with the frequency higher and lower than the atomic transition frequency, the atomic system, under some conditions, is heated up. The value of the critical temperature is found, which separates the regions where the collision-induced spontaneous decay is exothermic and endothermic.
Using climate, energy, and spatial-based hypotheses to interpret macroecological patterns of North America chelonians
Authors: Ennen Joshua R. , Agha Mickey , Matamoros Wilfredo A. , Hazzard Sarah C. , Lovich Jeffrey E.
Published: April 2016

Our study investigates how factors, such as latitude, productivity, and several environmental variables, influence contemporary patterns of the species richness in North American turtles. In particular, we test several hypotheses explaining broad-scale species richness patterns on several species richness data sets: (i) total turtles, (ii) freshwater turtles only, (iii) aquatic turtles, (iv) terrestrial turtles only, (v) Emydidae, and (vi) Kinosternidae. In addition to spatial data, we used a combination of 25 abiotic variables in spatial regression models to predict species richness patterns. Our results provide support for multiple hypotheses related to broad-scale patterns of species richness, and in particular, hypotheses related to climate, productivity, water availability, topography, and latitude. In general, species richness patterns were positively associated with temperature, precipitation, diversity of streams, coefficient of variation of elevation, and net primary productivity. We also found that North America turtles follow the general latitudinal diversity gradient pattern (i.e., increasing species richness towards equator) by exhibiting a negative association with latitude. Because of the incongruent results among our six data sets, our study highlights the importance of considering phylogenetic constraints and guilds when interpreting species richness patterns, especially for taxonomic groups that occupy a myriad of habitats.
Capturing Requirements from Expected Interactions Between Software and Its Interactive Environment: An Ontology Based Approach
Authors: Chen Xiaohong , Jin Zhi
Published: April 2016

Requirements elicitation is one of the most important and challenging issues in requirements engineering. This paper proposes a systematic approach for capturing the software requirements from the expected interactions between the software-to-be and its interactive environment. Firstly, the software environment ontology and the interaction ontology are developed for serving as the meta-models for the descriptions of the interactive environment and the interactions. Then a process has been proposed for guiding the analysts to capture the software requirements step by step from descriptions of the interactive environment and the expected interactions. Finally, a case study has been presented for illustrating the usage of our approach.
Analysis of a viscosity model for concentrated polymers
Authors: Bulíček Miroslav , Gwiazda Piotr , Süli Endre , Świerczewska-Gwiazda Agnieszka
Published: April 2016

The paper is concerned with a class of mathematical models for polymeric fluids, which involves the coupling of the Navier–Stokes equations for a viscous, incompressible, constant-density fluid with a parabolic–hyperbolic integro-differential equation describing the evolution of the polymer distribution function in the solvent, and a parabolic integro-differential equation for the evolution of the monomer density function in the solvent. The viscosity coefficient, appearing in the balance of linear momentum equation in the Navier–Stokes system, includes dependence on the shear rate as well as on the weight-averaged polymer chain length. The system of partial differential equations under consideration captures the impact of polymerization and depolymerization effects on the viscosity of the fluid. We prove the existence of global-in-time, large-data weak solutions under fairly general hypotheses.
Representation growth of the Heisenberg group over 𝒪[x]/(x3)
Authors: Dung Duong Hoang
Published: April 2016

We present a conjectured formula for the representation of zeta function of the Heisenberg group over [Formula: see text], where [Formula: see text] is the ring of integers of some number field. We confirm the conjecture for [Formula: see text].
Ehapp2: Estimate haplotype frequencies from pooled sequencing data with prior database information
Authors: Cao Chang-Chang , Sun Xiao
Published: April 2016

To reduce the cost of large-scale re-sequencing, multiple individuals are pooled together and sequenced called pooled sequencing. Pooled sequencing could provide a cost-effective alternative to sequencing individuals separately. To facilitate the application of pooled sequencing in haplotype-based diseases association analysis, the critical procedure is to accurately estimate haplotype frequencies from pooled samples. Here we present Ehapp2 for estimating haplotype frequencies from pooled sequencing data by utilizing a database which provides prior information of known haplotypes. We first translate the problem of estimating frequency for each haplotype into finding a sparse solution for a system of linear equations, where the NNREG algorithm is employed to achieve the solution. Simulation experiments reveal that Ehapp2 is robust to sequencing errors and able to estimate the frequencies of haplotypes with less than 3% average relative difference for pooled sequencing of mixture of real Drosophila haplotypes with 50× total coverage even when the sequencing error rate is as high as 0.05. Owing to the strategy that proportions for local haplotypes spanning multiple SNPs are accurately calculated first, Ehapp2 retains excellent estimation for recombinant haplotypes resulting from chromosomal crossover. Comparisons with present methods reveal that Ehapp2 is state-of-the-art for many sequencing study designs and more suitable for current massive parallel sequencing.
Multi-agent system simulation for urban policy design: open space land use change problem
Authors: Buil Roman , Piera Miquel Angel , Ginters Egils
Published: April 2016

Multi-agent system (MAS) models have been increasingly applied to the simulation of complex phenomena in different areas, providing successful and credible results. Citizens behavior related to a specific urban activity (i.e., recreation activities in a park, using bicycle for mobility purposes) can be modeled as an agent (actor) with several affinities and preferences which are dependent on aspects that affect the activity. A particular application of a MAS approach is in area of urban policy design, in which policies should be designed considering citizens needs, preferences and behavior. Once an open space in a city is available (i.e., an industry is moved to an industrial area), a land use policy should contribute to identify the new use for the urban space. There are different land use policies that can be applied depending on which services or facilities must be empowered in the city. It is important to identify the correct policy in order to satisfy present citizens needs but considering also the future needs in a social changing context. A socio-technological simulation model has been developed to allow citizens to get a better understanding of the urban problem, its dynamics and explore the sustainability of the different solutions., enhancing citizens to participate in the urban decisions through new technologies (i.e., e-participation). This paper illustrates an open space MAS simulation model for land use design policies in which citizens can check their opinion and get a better understanding of the different choices and its acceptability by the community considering not only present neighborhood profiles, but also future neighborhood configurations. It is the first step before the development of the final software including a user friendly interface to let citizens with different cultural profiles to perform simulations as an essential and neutral tool to reach consensus during the decision-making process in urban policy design.
The End of (Numeric) Error
Authors: Tichy Walter
Published: April 2016

Crunching numbers was the prime task of early computers. The common element of these early computers is they all used integer arithmetic. John Gustafson, one of the foremost experts in scientific computing, has proposed a new number format that provides more accurate answers than standard floats, yet saves space and energy. The new format might well revolutionize the way we do numerical calculations.
Rab25 influences functional Cav1.2 channel surface expression in arterial smooth muscle cells
Authors: Bannister John P. , Bulley Simon , Leo M. Dennis , Kidd Michael W. , Jaggar Jonathan H.
Published: April 2016

Plasma membrane-localized CaV1.2 channels are the primary calcium (Ca2+) influx pathway in arterial smooth muscle cells (myocytes). CaV1.2 channels regulate several cellular functions, including contractility and gene expression, but the trafficking pathways that control the surface expression of these proteins are unclear. Similarly, expression and physiological functions of small Rab GTPases, proteins that control vesicular trafficking in arterial myocytes, are poorly understood. Here, we investigated Rab proteins that control functional surface abundance of CaV1.2 channels in cerebral artery myocytes. Western blotting indicated that Rab25, a GTPase previously associated with apical recycling endosomes, is expressed in cerebral artery myocytes. Immunofluorescence Förster resonance energy transfer (immunoFRET) microscopy demonstrated that Rab25 locates in close spatial proximity to CaV1.2 channels in myocytes. Rab25 knockdown using siRNA reduced CaV1.2 surface and intracellular abundance in arteries, as determined using arterial biotinylation. In contrast, CaV1.2 was not located nearby Rab11A or Rab4 and CaV1.2 protein was unaltered by Rab11A or Rab4A knockdown. Rab25 knockdown resulted in CaV1.2 degradation by a mechanism involving both lysosomal and proteasomal pathways and reduced whole cell CaV1.2 current density but did not alter voltage dependence of current activation or inactivation in isolated myocytes. Rab25 knockdown also inhibited depolarization (20–60 mM K+) and pressure-induced vasoconstriction (myogenic tone) in cerebral arteries. These data indicate that Rab25 is expressed in arterial myocytes where it promotes surface expression of CaV1.2 channels to control pressure- and depolarization-induced vasoconstriction.
Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo
Authors: Fung Thomas K. , Law Clayton S. , Leung L. Stan
Published: April 2016

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing—generating synaptic excitation before a spike—results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of −10 to 0 ms resulted in significant input-specific LTP of the basal dendritic excitatory sink, lasting 60–120 min. Pairing at +10- to +20-ms ES intervals, or unpaired 5-Hz stimulation, did not induce significant basal dendritic or apical dendritic LTP or LTD. No basal dendritic LTD was found after stimulation of stratum oriens with 200 pairs of high-intensity pulses at 25-ms interval. Pairing-induced LTP was abolished by pretreatment with an N-methyl-d-aspartate receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which also reduced spike bursting during 5-Hz pairing. Pairing at 0.5 Hz did not induce spike bursts or basal dendritic LTP. In conclusion, ES pairing at 5 Hz resulted in input-specific basal dendritic LTP at ES intervals of −10 ms to 0 ms but no LTD at ES intervals of −20 to +20 ms. Associative LTP likely occurred because of theta-rhythmic coincidence of subthreshold excitation with a backpropagated spike burst, which are conditions that can occur naturally in the hippocampus.
Methotrexate Hepatotoxicity in Psoriatics: Report of 104 Patients from Nova Scotia, with Analysis of Risks from Obesity, Diabetes and Alcohol Consumption During Long Term Follow‐Up
Authors: Malatjalian DA , Ross JB , Williams CN , Colwell SJ , Eastwood BJ
Published: April 2016

BACKGROUND AND DESIGN: Methotrexate (MTX) hepatotoxicity in psoriatic patients is well recognized, but there are discrepancies in the reported incidence and associated risk factors. This retrospective study describes 104 Nova Scotian patients with psoriasis seen between 1979 and 1990. Patients received MTX over one to 11 years (mean 3.38), with baseline and annual follow‐up liver biopsies. Clinical data were obtained by chart review. Statistical analysis evaluated the risks associated with obesity, diabetes, alcohol consumption and duration of therapy, with the histological grade of liver biopsies.

RESULTS: Of the 104 patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol. At the end of the study, 21 patients had developed severe hepatic fibrosis (grade IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe hepatotoxicity is related to diabetes (P=0.02) but not to obesity (P=0.12) or alcohol consumption (P=0.12). All patients with cirrhosis took MTX for two years in standard doses of 20 to 25 mg/week.

CONCLUSIONS: In this first Canadian study evaluating MTX hepatotoxicity in psoriatics, the incidence of severe hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that diabetic patients are particularly at increased risk of MTX hepatotoxicity. Occasional alcohol consumption is not associated with increased risk. Three patients who developed cirrhosis over two years of standard MTX therapy may represent a subset of psoriatics with increased hepatic susceptibility to MTX. Another three patients whose severe hepatic fibrosis had regressed upon discontinuation of MTX, but who developed accelerated recurrence of the severe hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of unusual sensitivity to the drug. These cases emphasize the need for continuing surveillance, with regular liver biopsies, of psoriatic patients on MTX.
Functional Asplenia and Microscopic (Collagenous) Colitis
Authors: Freeman Hugh James
Published: April 2016

A 54-year-old female presented with a pulmonary infection that resolved completely with antibiotic treatment. Peripheral blood films showed features characteristic of splenic hypofunction, and radiolabelling studies confirmed an absence of splenic reticulo-endothelial cell activity, which is typical of functional asplenia. The patient had a remote history of watery diarrhea but no clinical and laboratory features of malabsorption. Extensive upper and lower gastrointestinal tract biopsy studies revealed histopathological features of collagenous colitis without gastric or small intestinal inflammatory changes or epithelial lymphocytosis. Hyposplenism has been associated with different gastrointestinal disorders, particularly celiac disease. This is the first report of functional asplenia and microscopic collagenous colitis.
Ultrasound-Guided Extracorporeal Shock Wave Lithotripsy of Pancreatic Ductal Stones: Six Years’ Experience
Authors: Johanns Werner , Jakobeit Christian , Greiner Lucas , Janssen Jan
Published: April 2016

Extracorporeal shock wave lithotripsy (ESWL) and endoscopic sphincterotomy (EST) was performed in 35 patients suffering from pancreatic duct stones. Calculi disintegration and resolution of obstruction were achieved in all cases. Completely stone-free ducts were achieved in 16 patients (46%) while some peripheral asymptomatic stone material remained in 19 (54%). Dilation of the main pancreatic duct was reduced in 29 patients (83%). Twelve patients (34%) became completely asymptomatic and 17 (49%) reported a marked reduction of pain. Pancreatogenic steatorrhea ceased and 18 patients (51%) gained weight. Pathological glucose tolerance returned to normal in one patient. No major complications were observed. The combination of ESWL and EST is a successful, nonoperative, new treatment in pancreatic stone disease.
Clinical Aspects of Trace Elements: Zinc in Human Nutrition ‐ Assessment of Zinc Status
Authors: Pluhator Michelle M , Thomson Alan Br , Fedorak Richard N
Published: April 2016

Because the limiting and vulnerable zinc pool has not been identified, it becomes a challenge to determine which of the many zinc pools is most susceptible to deficiency. As a consequence, defining and assessing zinc status in the individual patient is a somewhat uncertain process. Laboratory analysis of zinc status is difficult because no single biochemical criterion can reliably reflect zinc body stores. Many indexes have been examined in the hopes of discovering a method for the assessment of zinc nutriture. None of the methods currently used can be wholeheartedly recommended because they are fraught with problems that affect their use and interpretation. However, these methods remain in use for clinical and research purposes, though their benefits and drawbacks must always be acknowledged. Until an acceptable method of analysis is discovered, clinicians must rely for confirmation of zinc deficiency on a process of supplementing with zinc and observing the patient’s response. The main indexes (plasma/serum, erythrocyte, leukocyte, neutrophil, urine, hair and salivary zinc levels, taste acuity and oral zinc tolerance tests, and measurement of metallothionein levels) are reviewed. Measurement of plasma or erythrocyte metallothionein levels shows promise as a future tool for the accurate determination of zinc status.
Clinical Aspects of Trace Elements: Zinc in Human Nutrition – Zinc Deficiency and Toxicity
Authors: Pluhator Michelle M , Thomson Alan Br , Fedorak Richard N
Published: April 2016

Available evidence suggests that trace elements, such as zinc, once thought to have no nutritional relevance, are possibly deficient in large sections of the human population. Conditioned deficiencies have been reported to result from malabsorption syndromes, acrodermatitis enteropathica, alcoholism, gastrointestinal disease, thermal injury, chronic diseases (eg, diabetes, sickle cell anemia), and in total parenteral nutrition therapy. Awareness that patients with these problems are at risk has led health professionals to focus increasingly on the importance of zinc therapy in the prevention and treatment of deficiency. More recently zinc toxicity and its role in human nutrition and well‐being have come under investigation. Reports have focused on the role of zinc toxicity in causes of copper deficiency, changes in the immune system and alterations in blood lipids. As the numerous challenges presented by the study of zinc in human nutrition are met, more appropriate recommendations for dietary and therapeutic zinc intake are being made.
The Enteric Nervous System in Intestinal Inflammation
Authors: Sharkey Keith A , Parr Edward J
Published: April 2016

Since about the 1950s nerves in the wall of the intestine have been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD). Human and animal studies examining the role of nerves in intestinal inflammation are the focus of this review. Consideration is given to two possible ways that nerves are involved in IBD. First, nerves may play a role in the development or maintenance of inflammation through local release of transmitters. Second, once initiated (by whatever means), the processes of inflammation may disrupt the normal pattern of innervation and the interactions of nerves and their target tissues. Many of the functional disturbances observed in IBD are likely due to an alteration in the enteric nervous system either structurally through disruptions of nerve‐target relationships or by modifications of neurotransmitters or their receptors. Finally, it appears that the enteric nervous system may be a potential therapeutic target in IBD and that neuroactive drugs acting locally can represent useful agents in the management of this disease.
Segmental Colitis Complicating Diverticular Disease
Authors: Van Rosendaal Guido Ma , Andersen Melvin A
Published: April 2016

Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients with underlying diverticulosis are presented. Segmental resection has permitted close review of the histopathology in this syndrome which demonstrates considerable similarity to changes seen in idiopathic ulcerative colitis. The reported experience with this syndrome and its clinical features are reviewed.
Transanal Excision of Anorectal Tumors Using the Multifire EndogiaTM 30
Authors: O’Connor John J
Published: April 2016

Transanal excision of rectal tumours is a viable technique for the removal of benign lesions and early small carcinomas. This report describes a technique for their early removal with the Endo‐GIA stapling device.
Fulminant Liver Failure with Necrotizing Foci in the Liver, Spleen and Lymph Nodes in Celiac Disease Due to Malignant Lymphoma
Authors: Freeman Hugh James
Published: April 2016

A 65-year-old female with celiac disease developed cholestatic jaundice and fatal liver failure. Investigations revealed widespread necrotic foci in the liver, spleen and mesenteric lymph nodes, changes reminiscent of the mesenteric lymph node cavitation syndrome, which is known to complicate celiac disease. In addition, malignant lymphoid cells were present infiltrating hepatic sinusoids, lymph nodes and spleen. These features are typical of hepatosplenic lymphoma, a rare type of peripheral T cell lymphoma with T cell receptor rearrangement. Lymphorecticular malignancy complicating celiac disease may present with fulminant liver disease.
Duodenal Obstruction from Congenital Bands: An Unusual Cause of Pancreatitis
Authors: Just JD , Bailey RJ
Published: April 2016

Acute pancreatitis in children has many different causes. An unusual case of pancreatitis is presented, along with a review of some of the factors associated with pancreatitis in children. The probable pathogenesis of pancreatitis in this case is also discussed.
Diagnosis and Management of AIDS-related Diarrhea
Authors: Johanson John F
Published: April 2016

The spectrum of illness associated with the acquired immunodeficiency syndrome (AIDS) has been increasing since the initial description in 1981. While virtually all organ systems may be affected, the gastrointestinal tract appears to be a major target. Diarrhea is the most common symptom, affecting up to half of all AIDS patients during the course of their disease. Although diarrhea occurs frequently, its optimal management remains controversial. An extensive evaluation including stool studies and endoscopic biopsies of both the colon and small intestine has been widely recommended to identify all potential pathogenic organisms. An alternative approach is a more limited evaluation consisting of stool and blood cultures followed by symptomatic treatment with antidiarrheal agents if no specific organisms are identified. The clinical presentation of the most common opportunistic pathogens are reviewed, including several recently discovered organisms. Recommendations for treatment are followed by a brief discussion of management strategies used to care for patients with AIDS-related diarrhea.
Brain‐Gut Interactions in Inflammatory Bowel Disease: Mechanisms of Anorexia in Animal Models of Experimental Colitis
Authors: Weingarten Harvey P
Published: April 2016

Physiological processes within the bowel are influenced constantly by signals from other organs, primarily the brain. The mechanisms by which inflammation of the gastrointestinal tract results in anorexia are unknown. Understanding how the inflammation‐related signals in the periphery are communicated to the central nervous system and activate cytokine production in the brain remains an enormous challenge. Elucidation of these gut‐brain communication mechanisms is essential to the development of appropriate and efficacious treatments for the eating and weight disturbances associated with inflammatory bowel disease.
AIDS‐Related Extrapulmonary Pneumocystis carinii Infection Presenting as a Solitary Rectal Ulcer
Authors: Yoshida Eric M , Filipenko Douglas , Phillips Peter , Montaner Julio SG , Whittaker J Scott
Published: April 2016

Extrapulmonary infection with Pneumocystis carinii, although uncommon, is increasingly recognized. Use of aerosolized pentamidine versus a systemic medication is thought to be a contributing factor due to the low concentrations of drug that are incapable of suppressing systemic infection. Infection with P carinii has been reported in every organ system including the gastrointestinal system. A 28‐year‐old acquired immunodeficiency syndrome patient receiving prophylaxis with aerosolized pentamidine who presented with a solitary rectal ulcer is reported. Initial biopsy was characteristic of extrapulmonary P carinii infection, with numerous organisms present. Occasional cytomegalovirus inclusion bodies were noted which may have been a copathogen but which were not treated. Treatment with intravenous pentamidine resulted in documented eradication of P carinii and complete resolution of the ulcer. Although lower gastrointestinal pneumocystosis has been described without ulceration, this is the first description of rectal ulceration presenting as the initial manifestation of extrapulmonary pneumocystosis.
Appropriateness of Liver Biopsy
Authors: Poynard Thierry , Ratziu Vlad , Bedossa Pierre
Published: April 2016

This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heterogeneous opinions concerning the appropriateness of liver biopsy. Appropriateness should be evaluated for different techniques such as percutaneous liver biopsy, guided or not by ultrasonography, and the types of needles, automatic or not. The present paper reviews the evaluation of liver biopsy appropriateness in the real world, the adverse events and mortality of liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease and chronic hepatitis C. The authors conclude that liver biopsy is used extensively, but its appropriateness has not been evaluated perfectly. Therefore, further evaluation of the appropriateness of liver biopsy in the practical algorithm of such diseases is needed.
Increased Prevalence of Celiac Disease in Girls with Turner Syndrome Detected Using Antibodies to Endomysium and Tissue Transglutaminase
Authors: Gillett PM , Gillett HR , Israel DM , Metzger DL , Stewart L , Chanoine J-P , Freeman HJ
Published: April 2016

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia.

METHODS: Forty‐five girls with TS were prospectively screened for CD using blinded testing with the current ’gold standard’ ‐ immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten‐free diet was recommended if CD was confirmed.

RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy.

CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy‐confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.
Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part C: Protein Synthesis and Post-Translational Processing in Eukaryotic Cells
Authors: Wild Gary E , Papalia Patrizia , Ropeleski Mark J , Faria Julio , Thomson Alan BR
Published: April 2016

The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.
Helicobacter pyloriAntibiotic Resistance: Trends Over Time
Authors: Lahaie Raymond G , Gaudreau Christiane
Published: April 2016

Resistance to antibiotics can be a major problem in the treatment of bacterial infections. As the use of antibiotics increases, bacterial resistance to these agents is rising and in many cases is responsible for the failure of treatment regimens. Although the treatment ofHelicobacter pyloriinfection requires the use of more than one antibiotic to obtain adequate eradication rates, the efficacy of the currently used antibiotic combinations has been shown to be decreased by resistance to one of the antibiotics. The use of antibiotics in regimens for the treatment ofH pyloriis increasing in many countries, including Canada. This increase is both in the use of these antibiotics alone for the treatment of nongastrointestinal infections and in their use in association with proton pump inhibitors for the treatment ofH pyloriinfection. In several European and Asian countries, where resistance to antibiotics is being monitored, it has been demonstrated thatH pyloriresistance to metronidazole and to clarithromycin increased throughout the 1990s. Thus far, the data available in Canada do not show increased resistance to either of these antibiotics. As for other antibiotics used in the treatment ofH pyloriinfection, such as tetracycline and amoxicillin, the rate of resistance to these agents is still very low and does not constitute a significant problem. Because the efficacy of the regimens used in the treatment ofH pyloriinfection is compromised by resistance to the antibiotics used, it is important thatH pyloriresistance rates in Canada and throughout the world continue to be monitored. Only with such reliable data can the most optimal regimens be recommended.
Do NSAIDs Prevent Colorectal Cancer?
Authors: Arber Nadir
Published: April 2016

There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumours per animal and fewer animals with tumours after administration of several different NSAIDs. Studies in humans consistently support this hypothesis. Intervention data from familial adenomatosis coli establish that the process of human colonic adenoma polyp formation is affected. Supportive evidence comes from 21 of 23 human studies -- both case-control and cohort. The reduced risk has been found in men and women, for cancers of the colon and the rectum and for the use of both ASA and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. The molecular mechanisms responsible for the chemopreventive action of this class of drugs is not completely established. Protection may affect several pathways, including cell cycle arrest and induction of apoptosis.  Because of the consistency of epidemiological, clinical and experimental data, there is no need for further placebo trials. At the same time, there is a need to establish the dose, duration and frequency of use required for cancer-preventive activity.