bluuebunny/crossref_metadata_2025 huggingface dataset:
A long noncoding RNA associated with susceptibility to celiac disease
Authors: Castellanos-Rubio Ainara , Fernandez-Jimenez Nora , Kratchmarov Radomir , Luo Xiaobing , Bhagat Govind , Green Peter H. R. , Schneider Robert , Kiledjian Megerditch , Bilbao Jose Ramon , Ghosh Sankar
Published: March 2016

Long noncoding RNAs in inflammation

Growing evidence suggests that long noncoding RNAs (lncRNAs) are important modulators of gene expression. Castellanos-Rubio
et al.
identified a lncRNA, lnc13, that suppresses inflammatory gene expression in macrophages (see the Perspective by Huarte). Lnc13 interacts with proteins that regulate chromatin accessibility. Stimulating macrophages with a cell wall component from bacteria decreased expression of lnc13 and increased the expression of several inflammatory genes. Decreased levels of lnc13 in intestinal tissue from individuals with celiac disease hint that lnc13 may also play a role in the pathogenesis of immune-mediated diseases.

Science
, this issue p.
91
; see also p.
43
Mitochondrial disease therapy from thin air?
Authors: Shoubridge Eric A.
Published: March 2016

Low-oxygen treatment slows neurodegeneration in a model of a mitochondrial disorder

[Also see Research Article by

Jain
et al.

]
The Human Papillomavirus 16 E7 Oncoprotein Attenuates AKT Signaling To Promote Internal Ribosome Entry Site-Dependent Translation and Expression of c-MYC
Authors: Strickland Sydney Webb , Vande Pol Scott
Published: March 2016

While the role of high-risk human papillomavirus (HPV) oncoproteins E6 and E7 in targeting p53 and retinoblastoma (Rb) has been intensively studied, how E6 and E7 manipulate cellular signaling cascades to promote the viral life cycle and cancer development is less understood. Keratinocytes containing the episomal HPV-16 genome had decreased activation of AKT, which was phenocopied by HPV-16 E7 expression alone. Attenuation of phosphorylated AKT (pAKT) by E7 was independent of the Rb degradation function of E7 but could be ablated by a missense mutation in the E7 carboxy terminus, H73E, thereby defining a novel structure-function phenotype for E7. Downstream of AKT, reduced phosphorylation of p70 S6K and 4E-BP1 was also observed in E7-expressing keratinocytes, which coincided with an increase in internal ribosomal entry site (IRES)-dependent translation that enhanced the expression of several cellular proteins, including MYC, Bax, and the insulin receptor. The decrease in pAKT mediated by E7 is in contrast to the widely observed increase of pAKT in invasive cervical cancers, suggesting that the activation of AKT signaling could be acquired during the progression from initial productive infections to invasive carcinomas.

IMPORTANCEHPV causes invasive cervical cancers through the dysregulation of the cell cycle regulators p53 and Rb, which are degraded by the viral oncoproteins E6 and E7, respectively. Signaling cascades contribute to cancer progression and cellular differentiation, and how E6 and E7 manipulate those pathways remains unclear. The phosphoinositol 3-kinase (PI3K)/AKT pathway regulates cellular processes, including proliferation, cell survival, and cell differentiation. Surprisingly, we found that HPV-16 decreased the phosphorylation of AKT (pAKT) and that this is a function of E7 that is independent of the Rb degradation function. This is in contrast to the observed increase in AKT signaling in nearly 80% of cervical cancers, which typically show an acquired mutation within the PI3K/AKT cascade leading to constitutive activation of the pathway. Our observations suggest that multiple changes in the activation and effects of AKT signaling occur in the progression from productive HPV infections to invasive cervical cancers.
Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences
Authors: Jelen Mateja M. , Chen Zigui , Kocjan Boštjan J. , Hošnjak Lea , Burt Felicity J. , Chan Paul K. S. , Chouhy Diego , Combrinck Catharina E. , Estrade Christine , Fiander Alison , Garland Suzanne M. , Giri Adriana A. , González Joaquín Víctor , Gröning Arndt , Hibbitts Sam , Luk Tommy N. M. , Marinic Karina , Matsukura Toshihiko , Neumann Anna , Oštrbenk Anja , Picconi Maria Alejandra , Sagadin Martin , Sahli Roland , Seedat Riaz Y. , Seme Katja , Severini Alberto , Sinchi Jessica L. , Smahelova Jana , Tabrizi Sepehr N. , Tachezy Ruth , Tohme Faybush Sarah , Uloza Virgilijus , Uloziene Ingrida , Wong Yong Wee , Židovec Lepej Snježana , Burk Robert D. , Poljak Mario
Published: March 2016

Human papillomavirus 11
(HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B.

IMPORTANCE
This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.
B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts
Authors: Priyamvada Lalita , Cho Alice , Onlamoon Nattawat , Zheng Nai-Ying , Huang Min , Kovalenkov Yevgeniy , Chokephaibulkit Kulkanya , Angkasekwinai Nasikarn , Pattanapanyasat Kovit , Ahmed Rafi , Wilson Patrick C. , Wrammert Jens
Published: March 2016

Dengue virus (DENV) infection results in the production of both type-specific and cross-neutralizing antibodies. While immunity to the infecting serotype is long-lived, heterotypic immunity wanes a few months after infection. Epidemiological studies link secondary heterotypic infections with more severe symptoms, and cross-reactive, poorly neutralizing antibodies have been implicated in this increased disease severity. To understand the cellular and functional properties of the acute dengue virus B cell response and its role in protection and immunopathology, we characterized the plasmablast response in four secondary DENV type 2 (DENV2) patients. Dengue plasmablasts had high degrees of somatic hypermutation, with a clear preference for replacement mutations. Clonal expansions were also present in each donor, strongly supporting a memory origin for these acutely induced cells. We generated 53 monoclonal antibodies (MAbs) from sorted patient plasmablasts and found that DENV-reactive MAbs were largely envelope specific and cross neutralizing. Many more MAbs neutralized DENV than reacted to envelope protein, emphasizing the significance of virion-dependent B cell epitopes and the limitations of envelope protein-based antibody screening. A majority of DENV-reactive MAbs, irrespective of neutralization potency, enhanced infection by antibody-dependent enhancement (ADE). Interestingly, even though DENV2 was the infecting serotype in all four patients, several MAbs from two patients neutralized DENV1 more potently than DENV2. Further, half of all type-specific neutralizing MAbs were also DENV1 biased in binding. Taken together, these findings are reminiscent of original antigenic sin (OAS), given that the patients had prior dengue virus exposures. These data describe the ongoing B cell response in secondary patients and may further our understanding of the impact of antibodies in dengue virus pathogenesis.

IMPORTANCE
In addition to their role in protection, antibody responses have been hypothesized to contribute to the pathology of dengue. Recent studies characterizing memory B cell (MBC)-derived MAbs have provided valuable insight into the targets and functions of B cell responses generated after DENV exposure. However, in the case of secondary infections, such MBC-based approaches fail to distinguish acutely induced cells from the preexisting MBC pool. Our characterization of plasmablasts and plasmablast-derived MAbs provides a focused analysis of B cell responses activated during ongoing infection. Additionally, our studies provide evidence of OAS in the acute-phase dengue virus immune response, providing a basis for future work examining the impact of OAS phenotype antibodies on protective immunity and disease severity in secondary infections.
A neoteric multidrug combination: novel approach to limited cutaneous systemic scleroderma involving the face
Authors: Kumar M Hari , Kumar M Siva , Kumar Sabitha Hari , Kumar Kingsly Selva
Published: March 2016

Limited cutaneous scleroderma is a subtype of scleroderma limited to the skin of the face, hands, feet and forearms. We present a case of a 45-year-old woman affected by limited cutaneous systemic scleroderma involving the orofacial region and causing restricted mouth opening. The patient showed noteworthy improvement of the skin lesion by use of a combination of intralesional corticosteroid with hyaluronidase and various multiantioxidants, resulting in amelioration of her mouth opening problem. The patient gave her full informed written consent to this report being published.
Stress management for equine vets
Authors: Crowe Carolyne
Published: March 2016

Equine practice brings its own particular pressures, says Carolyne Crowe, who offers some advice on how to recognise and counteract the stress that might result.
Might dolutegravir be part of a functional cure for HIV?
Authors: Wainberg Mark A. , Han Ying-Shan , Mesplède Thibault
Published: March 2016

Antiretroviral therapy (ART) has greatly decreased HIV-related morbidity and mortality. However, HIV can establish viral reservoirs that evade both the immune system and ART. Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) related to the first-generation INSTIs raltegravir (RAL) and elvitegravir (EVG). DTG shows a higher genetic barrier to the development of HIV-1 resistance than RAL and EVG. More interestingly, clinical resistance mutations to DTG in treatment-naïve patients have not been observed to date. This review summarizes recent studies on strategies toward a cure for HIV, explores resistance profiles of DTG, and discusses how DTG might help in finding a functional cure for HIV.
Entropic motion in loop quantum gravity
Authors: García-Islas J. Manuel
Published: March 2016

Entropic forces result from an increase of the entropy of a thermodynamical physical system. It has been proposed that gravity is such a phenomenon and many articles have appeared in the literature concerning this problem. We propose a method that may reproduce an entropic force and may be related to loop quantum gravity. By considering the interaction between a fixed gravity state space and a particle state in loop quantum gravity, we show that it leads to a mathematical description of a random walk of such a particle. The random walk, in special situations, can be seen as an entropic motion in such a way that the particle will move towards a location where entropy increases. This may prove that such a theory can reproduce gravity as it is expected.
Spectroscopic investigation, HOMO–LUMO energies, natural bond orbital (NBO) analysis and thermodynamic properties of two-armed macroinitiator containing coumarin with DFT quantum chemical calculations
Authors: Akman Feride
Published: March 2016

In the present work, two-armed macroinitiator containing coumarin were synthesized, characterized by Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance techniques and investigated theoretically using density functional theory (DFT) calculations. The molecular geometry, fundamental vibrational frequencies, atomic charges obtained from atomic polar tensors and Mulliken were analyzed by means of structure optimizations based on the DFT method with 6-31G+(d, p) as a basis set. The 1H chemical shifts were calculated by the gauge-including atomic orbital method and compared with available experimental data. The electronic properties, such as highest occupied molecular orbital – lowest unoccupied molecular orbital (HOMO–LUMO) energies, electron affinity, electronegativity, ionization energy, hardness, chemical potential, global softness, and global electrophilicity were calculated by using the DFT method. The electrostatic potential and molecular electrostatic potential surfaces were performed to predict the reactive sites of the two-armed macroinitiator. The energy difference between acceptor and donor and stabilization energy were determined using natural bond orbital analysis. The results show that the occurrence of intramolecular charge transfers within the polymer. Time-dependent density functional theory calculations of visible spectra were analyzed at different solvents. Finally, thermodynamic functions, such as enthalpy, heat capacity, and entropy, of the two-armed macroinitiator at different temperatures were calculated and the relationship with temperature was investigated.
Combining Renyi Entropy and EWMA to Detect Common Attacks in Network
Authors: Yan Ruoyu
Published: March 2016

How to timely and precisely identify attack behaviors in network without dealing with a large number of traffic features and historical data, such as training data, is an important research work in the field of network security. In this paper, firstly, the differences between Renyi entropy and Shannon entropy are analyzed and compared. In order to capture network traffic changes exactly, Renyi entropy instead of Shannon entropy is proposed to measure selected traffic features. Then EWMA control chart theory is used to check Renyi entropy time series for detecting and screening anomalies. And three kinds of network attacks are also analyzed and characterized by behavior feature vector for attack identification. Finally a feature similarity-based method is used to identify attacks. The experimental results of real traffic traces show that the proposed method has good capability to detect and identify these attacks with less computation cost. To evaluate attack identification method conveniently, an approach is proposed to generate simulated attack traffics. Compared with Shannon entropy-based method, the experiments on simulation traffics show that Renyi entropy-based method has much higher overall accuracy, average precision and average true positive rate. Further comparison indicates the proposed method has more powerful performance to detect attacks than PCA-based method.
Hong Kong's Political Trends
Authors: LIM Tai Wei
Published: March 2016

Politically, Hong Kong's unease is with the level of control the Chinese central government exercises over the Special Administrative Region and how autonomy is perceived between the two. Against this backdrop of unease, 2015 was a challenging year for Hong Kong due to ongoing social debates and discontent over the cost of housing, income gaps and inequitable opportunities and job prospects due to inequitable wealth and resource distribution.
Risk evaluation, detection and simulation during effusive eruption disasters
Authors: Harris Andrew , De Groeve Tom , Carn Simon , Garel Fanny
Published: March 2016

Lava ingress into a vulnerable population will be difficult to control, so that evacuation will be necessary for communities in the path of the active lava, followed by post-event population, infrastructural, societal and community replacement and/or relocation. There is a pressing need to set up a response chain that bridges scientists and responders during an effusive crisis to allow near-real-time delivery of globally standard ‘products’ for a timely and adequate humanitarian response. In this chain, the scientific research groups investigating lava remote-sensing and modelling need to provide products that are both useful to, and trusted by, the crisis response community. Requirements for these products include (a) formats that can be immediately integrated into a crisis management procedure, and (b) in an agreed and stable standard. A review of current capability reveals that we are at a point where the community can provide such a response, as is the aim of the RED SEED (Risk Evaluation, Detection and Simulation during Effusive Eruption Disasters) working group. This book is the first production of this group and is intended not only as a directory of current capabilities and operational service providers, but also as a statement of intent and need, while providing a simulation designed to demonstrate how a truly pan-disciplinary response to an effusive crisis could work.
The robot apocalypse is here
Authors: Yang Jean
Published: March 2016

Many of us may think the robot apocalypse is far away. After all, the robots we know do not seem capable of taking over our world. This piece is about how the robot apocalypse is already here, though it may not look how we expect, and about what we can do to prevent anything truly apocalyptic from happening.
Big data and social netbanks
Authors: Geslevich-Packin Nizan , Lev-Aretz Yafit
Published: March 2016

Social netbanks hold much potential as alternative financial institutions that could better serve marginalized populations. But they bring with them a number of regulatory complications and informational risks. We explore the rise of big data and social netbanks, and describe some of the challenges they present.
Clinical Management of Inflammatory Bowel Disease: Beyond Disease Activity. I. Assessing Psychosocial Factors
Authors: Vallis T Michael , Turnbull Geoffrey K
Published: March 2016

Inflammatory bowel disease (IBD) is a chronic, relapsing disorder that can be very disabling to the patient and often leads to significant lifestyle problems (eg, emotional distress, social isolation, work impairment and disability). Available evidence strongly indicates that health status is influenced by psychosocial factors as well as disease activity. This is the first of a two-part series, the purpose of which is to provide a framework to guide the gastroenterologist in the assessment and management of psychosocial factors that impact on the health status of the IBD patient. Part I contains a review of existing approaches to assessment of psychosocial factors, which include focusing on psychosomatic or psychiatric factors. The growing body of evidence in support of a “biopsychosocial” approach to understanding and treating health status is reviewed. In this approach, distress and disability are not seen as due to psychopathology, but stemming directly from the experience of illness itself. Part II will focus on specific strategies to maximize psychosocial adjustment to this disabling illness.
Eosinophilic Gastroenteritis in a Patient with Ehlers-Danlos Syndrome - A Rare Combination
Authors: Al-Traif I , Jewell L , Thomson ABR
Published: March 2016

A case of eosinophilic gastroenteritis in a patient with Ehlers-Danlos syndrome who presented with abdominal pain, vomiting, diarrhea and profound weight loss is presented. Because of inability to tolerate glucocorticosteroids, symptoms were treated with sodium chromoglycate and an elemental diet given by jejunostomy. The patient did well on this program. The gastrointestinal manifestations of eosinophilic gastroenteritis and Ehlers-Danlos syndrome are reviewed as well as the treatment modalities available for eosinophilic gastroenteritis.
Thermal Methods for Therapy of Nonvariceal Bleeding
Authors: Fleischer David
Published: March 2016

This presentation addresses the thermal methods for therapy of nonvariceal bleeding. The following subtopics will be considered: overview of thermal options, combination therapy, data, technique, conclusions regarding peptic ulcer therapy and unique situations.
Signet Ring Cell Carcinoma of the Colon Radiologically Stimulating Ileocecal Tuberculosis
Authors: Kwan WC Peter , Freeman HJ
Published: March 2016

A 65-year-old East Indian woman with episodic vomiting and anemia had radiological evaluations showing calcified lymph nodes in the abdomen and chest, with narrowing of the ileocecal valve and ascending colon suggesting the possibility of ileoccal tuberculosis. Evaluations subsequently proved this to be a signet ring cell carcinoma of the colon with infiltration of the terminal ileum.
5-ASA Suppositories in Hemorrhoidal Disease
Authors: Gionchetti P , Campieri M , Belluzzi A , Brignola C , Miglioli M , Barbara L
Published: March 2016

Forty patients with active hemorrhoidal disease were entered into this double-blind trial, 20 of whom were randomized to treatment with 5-aminosalicylic acid (5-ASA) (500 mg) suppositories. Clinical and sigmoidoscopic assessment was carried out before the start of the trial and after two weeks of treatment. At the end of the study, 5-ASA suppositories showed results superior to those of placebo for all parameters evaluated (P<0.01). There were no adverse events reported related to the use of suppositories. 5-ASA suppositories are a valid therapeutic approach for hemorrhoidal disease as it reduces the intensity of all symptoms and significantly decreases congestion of the hemorrhoidal plexus.
Positive Correlation between Normal Serum Gastrin Concentrations and Antral and Duodenal G Cells
Authors: Yacoub WR , Thomson ABR , Sherbaniuk RW , Hooper P , Jewell LD
Published: March 2016

It is controversial whether there is a correlation between serum gastrin concentrations and the density of G cells in the antral or duodenal mucosa. In this study, endoscopically obtained antral and duodenal biopsies were stained immunocytochemically for gastrin and the G cells quantitated using an MOP Videoplan computer image analysis system. Studies were performed in 20 patients with acid-peptic disorders (gastric ulcer, n=5; duodenal ulcer, n=10; reflux esophagitis, n=4; and nonulcer dyspepsia, n=1). Correlations between antral and duodenal G cell densities, and basal- and food-stimulated serum gastrin concentrations within the normal range (less than 100 mg/L) – but not in those with elevated gastrin concentrations – support the postulate that alterations in G cell function are important in patients with acid-peptic disorders.
Childhood Peutz-Jeghers Syndrome: Diversity of Clinical Features and Complications, and Literature Review
Authors: Oliver Mark R , Scott R Brent , Eccles Robin C , Trevenen Cynthia , Meddings Jonathon B , Martin Steven R
Published: March 2016

This case report of a six-year-old child with Peutz-Jeghers syndrome illustrates the potential diversity of presenting gastrointestinal symptoms and signs including hematemesis, obstruction and recurrent intussusception. Endoscopy was useful in assessment, while endoscopic polypectomy and surgical resection were both necessary for management. The literature is reviewed and the possible role that this syndrome may have in the development of both gastrointestinal and nongastrointestinal tumours is highlighted.
Acute Fatty Liver of Pregnancy: A Review of Maternal Morbidity in 13 Patients Seen Over 12 Years in Nova Scotia
Authors: Hoare Connie D , Malatjalian Dickran A , Badley Bernard W , Sidorov Joseph J , Williams C Noel
Published: March 2016

OBJECTIVE: To review the maternal and fetal survival in all cases of acute fatty liver of pregnancy seen by the Division of Gastroenterology at Grace Maternity Hospital and the Victoria General Hospital from 1979-91.

DESIGN: A retrospective review of the clinical data obtained from the medical charts of 13 patients with a liver biopsy-based histopathological diagnosis of acute fatty liver of pregnancy.

SETTING: Grace Maternity Hospital, a tertiary care centre serving d1e Atlantic provinces. Twelve patients were subsequently transferred to Victoria General Hospital for postpartum management in the setting of the medical intensive care unit.

MAIN OUTCOME MEASURES: Classically, acute fatty liver of pregnancy is complicated by over 70% maternal and fetal mortality rate. Recent reports have indicated significantly improved maternal and fetal survival because of more awareness, improved management and the identification of milder forms of the disease.

RESULTS: In this study of 13 cases of acute fatty liver of pregnancy, maternal survival was 100% and fetal survival was 93%.

CONCLUSION: The excellent maternal and fetal survival in this series is attributed co awareness, close collaboration between obstetricians and gastroenterologists, prompt diagnosis and delivery and the management of postpartum patients in an intensive care unit setting.
Immunosppressive Agents in Inflammatory Bowel Disease: Current Status and Future Prospects
Authors: Shanahan Fergus , O'’Sullivan Gerald C , Collins J Kevin
Published: March 2016

Inflammatory bowel disease involves an interaction between genetic susceptibility factors and environmental triggers, and the intestinal injury is mediated by the host immunoinflammatory response. Identification of the mechanisms and mediators that contribute to the tissue injury has provided a sound rationale for the therapeutic use of immunosuppressive and immunomodulatory agents. The efficacy of traditional immunosuppressive drugs, such as the purine analogues in both Crohn’s disease and ulcerative colitis, is well established. The major limitation of the use of these drugs is the delayed clinical response associated with their use. This has prompted an evaluation of other immunosuppressivcs, such as cyclosporine and related drugs, that have a more rapid onset of action. Convincing data indicate a distinct role for cyclosporine in certain patients with acute severe ulcerative colitis. However, despite early promising results with cyclosporine in Crohn’s disease, recent results have been less encouraging. There is also uncertainty about the exact clinical role of cyclosporine because of concerns regarding long term toxicity. At present, many investigators regard cyclosporine as an interim measure for acutely ill patients. The challenge that remains is the development of novel immunomodulatory strategies that are specific for the mucosal immune system and that are based on recent advances in our understanding of the pathogenesis of mucosal inflammation.
Ultrasound Demonstration of a Benign Gastric Ulcer with Gastric Outlet Obstruction
Authors: Pattee PL , Tao HH , Bhargava R , Al-Alwadhi A
Published: March 2016

A benign antral gastric ulcer in an adult causing gastric outlet obstruction was demonstrated by ultrasonography. The extent and benign nature of the ulcer was suggested by ultrasound before gastric surgery was performed. Features implying a benign gastric ulcer were: observation of peristaltic waves through the underlying muscular layer, homogenicity of the ulcer crater and characteristic mound or volcano-like appearance of the heaped-up folds of mucosa. The differential diagnosis and the role of ultrasound in the diagnosis of gastric ulcers are discussed.
Failure of Splenectomy to Ameliorate Portal Hypertension in Myeloproliferative Disorders
Authors: Lee Samuel S , Van Rosendaal Guido , Lay Thomas E , Kelly James K , Pineo Graham F
Published: March 2016

The correct treatment of portal hypertension associated with myeloproliferative disorders remains uncertain. Splenectomy has been advocated by some to eliminate the forward flow component of the portal hypertension and thus reduce portal pressure. The authors describe three recent cases of myeloproliferative disorder in whom splenectomy failed to achieve any significant amelioration of portal hypertension, with in-depth hemodynamic studies in one patient. Based on these experiences, the authors suggest that splenectomy is not the optimum treatment of the portal hypertension associated with myeloproliferative disorders.
Fructose and/or Sorbitol Intolerance in a Subgroup of Lactose Intolerant Patients
Authors: Mishkin SR , Sablauskas L , Mishkin S
Published: March 2016

The diagnosis and treatment of lactose intolerance often does not resolve all the symptoms of postcibal bloating and flatulence. Included in this study were 104 lactose intolerant patients (71 female, 33 male) who complained of residual postcibal discomfort in spite of adherence to and benefit from appropriate measures for their documented lactose intolerance (at least 20 ppm H2after 25 g lactose as well as appropriate symptomatic discomfort). Clinical characteristics common to this group included: symptomatic diarrhea (12.5%), history of foreign travel (5.8%), endoscopic and pathological evidence of gastritis and helicobacter infection (19.2 and 8.7%, respectively), nonspecific abnormalities of small bowel follow-through (15.4%), Crohn’s disease (8.7%) and colonic cliverticulosis (14.4%). Intolerance co fructose (at least 10 ppm H2after 25 g fructose plus appropriate symptoms) or sorbitol (at least 10 ppm H2after 5 g sorbitol plus appropriate symptoms) was documented in 17.3 and 18.3%, respectively. Intolerance to both fructose and sorbicol (administered as separate challenges), more than twice as common as intolerance to either one alone, occurred in 41.4% and was independent of sex. In conclusion, additional carbohydrate intolerances contribute to postcibal discomfort in more than 75% of lactose intolerant patients who remain symptomatic in spite of adherence to appropriate measures for this condition. While 62% of all patients had benefited significantly (greater than 50%) from appropriate dietary measures and enzyme replacement for lactose intolerance, only 40% of those who were also fructose intolerant and 47% who were sorbitol intolerant benefited (greater than 50%) from appropriate dietary measures (no enzyme replacement yet available) for intolerance to these sugars.
Basic Science for the Clinical Gastroenterologist: A Review of the Recent Literature on the Small Bowel – Part II
Authors: Thomson ABR
Published: March 2016

In small bowel science, as in all parts of medicine, there has been a recent explosion of information. This is the second of a two-part series in which the scientific basis of clinical gastroenterology practice and its future are considered. Advances in understanding the mechanisms of intestinal transport are examined, followed by a perspective of intestinal adaptation in health and disease. The author also discusses clinically important areas of motility and bloodflow.
Iatrogenic Gallbladder Perforation Treated by Laparoscopic Cholecystectomy
Authors: Graham S , Hermann S , Depew WT , Pace RF
Published: March 2016

A case of gallbladder perforation with bile peritonitis resulting from a percutaneous needle biopsy of the liver is presented. Using laparoscopic cholecystectomy as the surgical management, the patient made a rapid and smooth recovery.
Successful Treatment of Hepatoportal Arteriovenous Fistula by Transcatheter Embolization with Steel Coils
Authors: Picton Taralyn D , Machan Lindsay , Davis Jennifer , Freeman Hugh J , Steinbrecher Urs P
Published: March 2016

Portal hypertension is most commonly caused by increased intrahepatic resistance as a result of cirrhosis, but can also occur as a result of abnormally high portal bloodflow. This article describes a patient with a history of remote liver trauma in whom portal hypertension and variceal bleeding were shown to be due to an arteriovenous fistula between the hepatic artery and portal vein. Transcatheter embolization with Gianturco coils resulted in obliteration of the fistula and normalization of portal pressures.
Colonic Diaphragm Disease in a Patient Receiving Long Term Diclofenac Therapy
Authors: Weiss Alan A , Owen David A
Published: March 2016

A 65-year-old woman who had been taking diclofenac for five years developed cramping central abdominal pain. Barium enema examination was negative, but colonoscopy revealed prominent mucosal folds in the right colon with areas of ulceration. Because of continued symptoms, a right hemicolectomy was performed, which showed four separate short segment strictures or diaphragms. This case demonstrates a rare complication of nonsteroidal anti-inflammatory agent therapy that should be considered in the differential diagnosis of unexplained abdominal pain.
Seasonal Pattern in the Relapses of Crohn's Disease and Ulcerative Colitis in British Columbia
Authors: Anderson Frank H , Zeng Lecheng
Published: March 2016

Ulcerative colitis (UC) reportedly has a seasonal variation of exacerbations. No seasonal variation of relapses in Crohn's disease (CD) has been reported. A retrospective study of the monthly distribution in the relapses of inflammatory bowel disease (IBD) demonstrated seasonality in both UC and CD. From 1971-93, 226 patients (CD=139, UC=87) with regular follow-ups for at least 13 consecutive months were analyzed. In the study period, 592 relapses occurred in CD patients and 300 in UC patients. The peak relapse seasons were autumn and winter and the lowest was summer, for both CD and UC. The seasonal pattern was independent of sex. These results support the view that seasonal factors may be involved in the relapse of IBD.
A Normal Appearing Duodenal Papilla in Familial Polyposis Need to be Biopsied: A Case Report
Authors: Schweiger Franzjosef , Radhi Jasim , Roberge Roger M
Published: March 2016

The upper gastrointestinal tract is the most common site of extracolonic neoplasms in patients with familial polyposis coli. The majority of these patients develops adenomas in the duodenal periampullary area, some of which progress to adenocarcinoma. Early diagnosis and long term endoscopic surveillance are widely recommended to prevent the development of invasive cancer by early treatment of these tumours. The authors report the case of an asymptomatic 50-year-old man with familial polyposis coli in whom an adenocarcinoma of the papilla was diagnosed by random biopsy in the presence of negative radiographic and endoscopic studies. This case emphasizes the importance of regular screening and endoscopic biopsies of the major duodenal papilla and periampullary region in polyposis patients.
Special Problems Associated with Surgical Trials in Inflammatory Bowel Disease
Authors: McLeod Robin S
Published: March 2016

It is well accepted that the randomized controlled trial (RCT) is the best design for determining treatment effectiveness. Despite this, the surgical literature, particularly in the area of inflammatory bowel disease, is replete with case series while there is a paucity of RCTs assessing surgical interventions. There certainly is no lack of questions to be answered and there is a lack of consensus on many issues. Why then are there so few RCTs? Unfortunately, it appears that surgeons in general are more accepting of evidence from case series. However, it also appears that there are certain issues that are unique to, or at least occur more frequently in, clinical trials assessing surgical interventions. The issues of special concern in surgical trials can broadly be categorized as methodological and feasibility issues. Methodological issues include difficulties in standardization of the procedure, deciding on the timing of the trial and prevention of bias when blinding may be difficult or impossible. All these are challenges, but do not preclude the performance of RCTs. On the other hand, feasibility issues may pose more of a challenge. Patients may refuse entry, particularly if they view the two treatments as ‘unequal’ (eg, medical versus surgical therapy) and irreversible (as they usually are in surgery). Patient accrual may be difficult given the variable patterns of disease and indications for surgery. Finally, unlike medical therapies which are controlled by regulating agencies, surgical procedures can simply be performed and there may be little incentive, and even some disincentives, for the surgeon to participate in a trial. Despite these difficulties, better evaluation of surgical therapies is required. Where possible, RCTs should be performed, but in situations where this is not possible other trial designs must be employed that may lack some of the rigour of an RCT but that are more rigorous than the uncontrolled case series.
Immune-Mediated Neutropenia and Thrombocytopenia in a Patient with Ulcerative Colitis: An Unusual Hematological Association with IBD
Authors: Kim Young-In , Brzezinski Aaron , Brandwein Joseph , Baker Jeffrey P
Published: March 2016

Hematological manifestations of inflammatory bowel disease (IBD) are well described in the literature. However, the combination of immune-mediated neutropenia and thrombocytopenia has only been reported once in association with IBD. A case is reported of immune-mediated neutropenia and thrombocytopenia in a patient with ulcerative colitis during a relapse. No obvious causes of these hematological abnormalities were found in the patient despite an exhaustive search. An immune-mediated process was confirmed by positive antineutrophil antibody and platelet-associated antibody in the patient’s serum, and the demonstration of binding of the patient’s immunoglobulin G to autologous neutrophils. The patient was treated with high-dose steroid, intravenous gamma-globulin and eventually splenectomy. The platelet count subsequently normalized; although the severe neutropenia recurred, it has subsequently improved without further treatment. Although a definitive cause-effect relationship cannot be established, the immune-mediated neutropenia and thrombocytopenia may be an unusual hematological manifestation associated with ulcerative colitis.
Small Bowel Review - Part I
Authors: Thomson ABR , Wild G
Published: March 2016

Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleosides, nucleotides and polyamines; salt and water absorption, and diarrhea, including antidiarrheal therapy and oral rehydration treatment; lipids (digestion and absorption, fatty acid binding proteins, intracellular metabolism, lipoproteins and bile acids); and metals (eg, iron) and vitamins.
Pancreaticoduodenal Tuberculosis Simulating Metastatic Ovarian Carcinoma
Authors: Zalev Arthur H , Sacks Jeffrey S , Warren Ralph E
Published: March 2016

A patient from Thailand presented with symptoms suggestive of peptic ulceration. Radiology showed an ulcerated duodenal stricture, a pancreaticoduodenal mass and extensive retroperitoneal lymphadenopathy suggestive of metastatic carcinoma. Tuberculosis was diagnosed only at laparotomy. The incidence of tuberculosis is increasing, and alimentary tuberculosis should be considered in patients from populations at risk presenting with obscure abdominal complaints or unexplained radiologic findings.
Helicobacter pyloriHighlights from the First Canadian Digestive Disease Week
Authors: Matisko Ann , Thomson Alan BR
Published: March 2016

The first annual Canadian Digestive Disease Week (CDDW) took place in Banff, Alberta from March 4 to 10, 1996. The CDDW meeting was attended by over 600 Canadian physicians, fellows and researchers, and included a Gastroenterology Fellows' Program, as well as Practitioners' and Scientific Programs. It was apparent from the posters and presentations thatHelicobacter pyloriresearch ongoing in Canada is at the leading edge. World leaders inH pyloriresearch spoke on topics ranging from the genetics ofH pyloriand the pathogenesis of its associated diseases, to the clinical challenge of successful eradication of infection. This overview summarizes the information aboutH pyloripresented at the 1996 CDDW.
Hepatitis B Infection and Liver Transplantation
Authors: Yoshida Eric M
Published: March 2016

Patients with chronic hepatitis B virus (HBV) infection have historically incurred high rates of allograft reinfection from extrahepatic reservoirs of HBV, with worse long term outcome compared with that of transplant recipients without HBV infection. As a result, chronic HBV infection has been considered a contraindication for transplantation. Prophylaxis against HBV recurrence, in the form of passive immunization with high dose hepatitis B hyperimmunoglobulin and the antiviral agent lamivudine, has recently been demonstrated to decrease the risk of reinfection. With appropriate prophylaxis, liver transplantation can be a viable proposition for patients with HBV infection. Past experience and current status of HBV infection and transplantation are reviewed, with emphasis on the issues surrounding prophylaxis.
Hepatopulmonary Syndrome Associated with Schistosomal Liver Disease
Authors: Al-Moamary Mohamed , Altraif Ibrahim
Published: March 2016

A 55-year-old man with schistosomal liver disease presented with shortness of breath, orthodeoxia, platypnea, cyanosis, marked digital clubbing and liver failure. Extensive investigation revealed no other etiology for liver disease apart from schistosomiases. The diagnosis of hepatopulmonary syndrome was based on clinical grounds, as well as abnormal arterial blood gases and positive contrast echocardiography. The patient underwent orthotopic liver transplantation, which was initially successful, but then died of respiratory complications and multi-organ failure on day 42 post-transplant. To the authors' knowledge this is the first report of hepatopulmonary syndrome associated with schistosomal liver disease.
Hereditary Colon Cancer
Authors: Gilchrist Dawna M
Published: March 2016

Hereditary colon cancer comprises approximately 10% of total colon cancer, a disease that affects 6% of the North American population. Knowledge of molecular genetics of familial adenomatous polyposis and hereditary nonpolyposis colon cancer has improved our diagnostic abilities and management, as well as furthered our understanding of the mechanisms of tumour initiation and progression.
Canadian Association of Gastroenterology Practice Guideline for Clinical Competence in Diagnostic and Therapeutic Endoscopic Retrograde Cholangiopancreatography
Authors: Cockeram Alan
Published: March 2016

This Practice Guideline is intended to assist individuals, training programs and credentialling bodies in understanding the training for and application of endoscopic retrograde cholangiopancreatography (ERCP), as well as in designating credentialling and maintenance of competence. The Canadian Association of Gastroenterology (CAG) Practice Guideline on training and credentialling provides the necessary background (1). Many of the principles outlined have been previously accepted by CAG (2).
Small Bowel Review: Part I
Authors: Thomson ABR , Hasan J , Keelan M , Wild G
Published: March 2016

In the past year there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 500 papers were assessed, and some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist.
The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema
Authors: Hermanrud Thorbjørn , Duus Nicolaj , Bygum Anette , Rasmussen Eva Rye
Published: March 2016

Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature.
Pricing Strategies in the Remanufacturing Market for the Uncertain Market Size in the Second Period
Authors: Deng Liurui , Yang Shenggang
Published: March 2016

Our main endeavor is to investigate the effect of the uncertain market size in the second period on the pricing strategies in the remanufacturing market. Observing the previous research, we find that the market size in the second period is always supposed to be certain. However, there is substantial empirical and experimental evidence that the market size in reality deviates from this assumption. In fact, though the market size in the first period is definitized, it is difficult to confirm the change of the market scale in the second period, since this change is affected by all kinds of elements, such as the awareness of environmental protection, some consumers’ psychological factors, and the related governments’ policies. Hence, we pay attention to the case in which the change rate of the market scale in the second period is random variable. We suppose that this rate satisfies uniform distribution on[0,2]. Underlying this assumption, we further provide an insight into the game-playing relationship between original equipment manufacturers (OEMs) and remanufacturers. Moreover, we delicately and subtly incorporate the game theory, stochastic analysis, adversarial risk analysis (ARA), and optimization methods into the pricing strategies in the remanufacturing market. Last but not least, considerable efforts and attempts have been made to subtly test the sensitivity of an optimal solution to the different parameters.
Netrin-1 Peptide Is a Chemorepellent inTetrahymena thermophila
Authors: Kuruvilla Heather , Schmidt Bradley , Song Stephanie , Bhajjan Marian , Merical Matthew , Alley Caleb , Griffin Christopher , Yoder David , Hein Josephine , Kohl Daniel , Puffenberger Cambria , Petroff David , Newcomer Elise , Good Kortney , Heston Graham , Hurtubise Anna
Published: March 2016

Netrin-1 is a highly conserved, pleiotropic signaling molecule that can serve as a neuronal chemorepellent during vertebrate development. In vertebrates, chemorepellent signaling is mediated through the tyrosine kinase, src-1, and the tyrosine phosphatase, shp-2.Tetrahymena thermophilahas been used as a model system for chemorepellent signaling because its avoidance response is easily characterized under a light microscope. Our experiments showed that netrin-1 peptide is a chemorepellent inT. thermophilaat micromolar concentrations.T. thermophilaadapts to netrin-1 over a time course of about 10 minutes. Netrin-adapted cells still avoid GTP, PACAP-38, and nociceptin, suggesting that netrin does not use the same signaling machinery as any of these other repellents. Avoidance of netrin-1 peptide was effectively eliminated by the addition of the tyrosine kinase inhibitor, genistein, to the assay buffer; however, immunostaining using an anti-phosphotyrosine antibody showed similar fluorescence levels in control and netrin-1 exposed cells, suggesting that tyrosine phosphorylation is not required for signaling to occur. In addition, ELISA indicates that a netrin-like peptide is present in both whole cell extract and secreted protein obtained fromTetrahymena thermophila.Further study will be required in order to fully elucidate the signaling mechanism of netrin-1 peptide in this organism.