bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of HIV-1 DNA Level Interfering with Reliability of HIV-1 RNA Quantification Performed on Dried Blood Spots Collected from Successfully Treated Patients
Authors: Zida Sylvie , Tuaillon Edouard , Barro Makoura , Kwimatouo Lekpa Franchard Arnaud , Kagoné Thérèse , Nacro Boubacar , Ouedraogo Abdoul Salam , Bolloré Karine , Sanosyan Armen , Plantier Jean-Christophe , Meda Nicolas , Sangaré Lassana , Rouzioux Christine , Rouet François , Kania Dramane
Published: March 2016

The impact of HIV-1 DNA coamplification during HIV-1 RNA quantification on dried blood spots (DBS) was explored. False-positive HIV RNA detection (22/62, 35%) was associated with high HIV-1 DNA levels. Specificity of HIV-1 RNA assays on DBS should be evaluated following manufacturer protocols on samples with HIV-1 DNA levels of ≥1,000 copies/10
6
peripheral blood mononuclear cells.
Conserved Tryptophan Motifs in the Large Tegument Protein pUL36 Are Required for Efficient Secondary Envelopment of Herpes Simplex Virus Capsids
Authors: Ivanova Lyudmila , Buch Anna , Döhner Katinka , Pohlmann Anja , Binz Anne , Prank Ute , Sandbaumhüter Malte , Bauerfeind Rudolf , Sodeik Beate
Published: March 2016

Herpes simplex virus (HSV) replicates in the skin and mucous membranes, and initiates lytic or latent infections in sensory neurons. Assembly of progeny virions depends on the essential large tegument protein pUL36 of 3,164 amino acid residues that links the capsids to the tegument proteins pUL37 and VP16. Of the 32 tryptophans of HSV-1-pUL36, the tryptophan-acidic motifs
1766
WD
1767
and
1862
WE
1863
are conserved in all HSV-1 and HSV-2 isolates. Here, we characterized the role of these motifs in the HSV life cycle since the rare tryptophans often have unique roles in protein function due to their large hydrophobic surface. The infectivity of the mutants HSV-1(17
+
)Lox-pUL36-WD/AA-WE/AA and HSV-1(17
+
)Lox-CheVP26-pUL36-WD/AA-WE/AA, in which the capsid has been tagged with the fluorescent protein Cherry, was significantly reduced. Quantitative electron microscopy shows that there were a larger number of cytosolic capsids and fewer enveloped virions compared to their respective parental strains, indicating a severe impairment in secondary capsid envelopment. The capsids of the mutant viruses accumulated in the perinuclear region around the microtubule-organizing center and were not dispersed to the cell periphery but still acquired the inner tegument proteins pUL36 and pUL37. Furthermore, cytoplasmic capsids colocalized with tegument protein VP16 and, to some extent, with tegument protein VP22 but not with the envelope glycoprotein gD. These results indicate that the unique conserved tryptophan-acidic motifs in the central region of pUL36 are required for efficient targeting of progeny capsids to the membranes of secondary capsid envelopment and for efficient virion assembly.

IMPORTANCE
Herpesvirus infections give rise to severe animal and human diseases, especially in young, immunocompromised, and elderly individuals. The structural hallmark of herpesvirus virions is the tegument, which contains evolutionarily conserved proteins that are essential for several stages of the herpesvirus life cycle. Here we characterized two conserved tryptophan-acidic motifs in the central region of the large tegument protein pUL36 of herpes simplex virus. When we mutated these motifs, secondary envelopment of cytosolic capsids and the production of infectious particles were severely impaired. Our data suggest that pUL36 and its homologs in other herpesviruses, and in particular such tryptophan-acidic motifs, could provide attractive targets for the development of novel drugs to prevent herpesvirus assembly and spread.
Diffuse descending necrotising mediastinitis and pleural empyema secondary to acute odontogenic infection resulting in severe dysphagia
Authors: Glen Peter , Morrison James
Published: March 2016

We report a case of acute odontogenic sepsis in a 59-year-old man, presenting with diffuse, descending necrotising mediastinitis complicated by pleural empyema. Despite surviving the odds, his recovery was complicated by severe dysphagia, resulting in gastrostomy feeding for 6 months. Until now, severe dysphagia following descending necrotising mediastinitis has been unreported.
Speaking out about physical harms from tobacco use: response to graphic warning labels among American Indian/Alaska Native communities
Authors: Patterson Silver Wolf David A , Tovar Molly , Thompson Kellie , Ishcomer Jamie , Kreuter Matthew W , Caburnay Charlene , Boyum Sonia
Published: March 2016

Objective

This study is the first to explore the impact of graphic cigarette labels with physical harm images on members of American Indian/Alaska Native (AI/AN) communities. The aim of this article is to investigate how AI/AN respond to particular graphic warning labels.

Methods

The parent study recruited smokers, at-risk smokers and non-smokers from three different age groups (youths aged 13–17 years, young adults aged 18–24 years and adults aged 25+ years) and five population subgroups with high smoking prevalence or smoking risk. Using nine graphic labels, this study collected participant data in the field via an iPad-administered survey and card sorting of graphic warning labels. This paper reports on findings for AI/AN participants.

Results

After viewing graphic warning labels, participants rated their likelihood of talking about smoking risks to friends, parents and siblings higher than their likelihood of talking to teachers and doctors. Further, this study found that certain labels (eg, the label of the toddler in the smoke cloud) made them think about their friends and family who smoke.

Conclusions

Given the influence of community social networks on health beliefs and attitudes, health communication using graphic warning labels could effect change in the smoking habits of AI/AN community members. Study findings suggest that graphic labels could serve as stimuli for conversations about the risks of smoking among AI/AN community members, and could be an important element of a peer-to-peer smoking cessation effort.
Assessing sociodemographic differences (or lack thereof) in prenatal diagnosis of congenital heart defects: a population-based study
Authors: Khoshnood Babak , Lelong Nathalie , Andrieu Thibaut , Houyel Lucile , Bonnet Damien , Jouannic Jean-Marie , Goffinet François
Published: March 2016

Objectives

Our main objective was to assess sociodemographic differences in the probability of prenatal diagnosis of congenital heart defects (CHD); we also looked at differences in termination of pregnancy for fetal anomaly (TOPFA).

Design

Prospective cohort observational study.

Setting

Population-based cohort of CHD (live births, TOPFA, fetal deaths) born to women residing in the Greater Paris area (Paris and its surrounding suburbs, N=317 538 total births).

Participants

2867 cases of CHD, including 2348 (82%) live births, 466 (16%) TOPFA and 53 (2%) fetal deaths.

Primary and secondary outcome measures

Differences in the probability of prenatal diagnosis by maternal occupation, geographic origin and place of residence; differences in the probability of TOPFA.

Results

29.1% (95% CI 27.5% to 30.8%) of all CHD were prenatally diagnosed. Probability of prenatal diagnosis was similar by maternal occupation, geographic origin and place of residence. In contrast, there were substantial differences in the probability of TOPFA by maternal geographic origin; differences by maternal occupation and place of residence were generally smaller and not statistically significant.

Conclusions

Our findings suggest that an appropriate health system organisation aimed at providing universal, reimbursed specialised services to all women can provide comparable access to prenatal diagnosis for all sociodemographic groups. In contrast, we found substantial differences in TOPFA for women of different geographic origins, which may reflect women's preferences that should be respected, but that can nonetheless lead to the situation where families with fewer resources will be disproportionately responsible for care of newborns with more severe forms of CHD.
Improving the management of behaviour that challenges associated with dementia in care homes: protocol for pharmacy–health psychology intervention feasibility study
Authors: Maidment Ian D , Shaw Rachel L , Killick Kirsty , Damery Sarah , Hilton Andrea , Wilcock Jane , Barnes Nigel , Brown Graeme , Gillespie Sarah , Fox Chris , Barton Garry , Iliffe Steve , Seare Nichola
Published: March 2016

Introduction

The inappropriate use of antipsychotics in people with dementia for behaviour that challenges is associated with an estimated 1800 deaths annually. However, solely focusing on antipsychotics may transfer prescribing to other equally dangerous psychotropics. Little is known about the role of pharmacists in the management of psychotropics used to treat behaviours that challenge. This research aims to determine whether it is feasible to implement and measure the effectiveness of a combined pharmacy–health psychology intervention incorporating a medication review and staff training package to limit the prescription of psychotropics to manage behaviour that challenges in care home residents with dementia.

Methods/analysis

6 care homes within the West Midlands will be recruited. People with dementia receiving medication for behaviour that challenges, or their personal consultee, will be approached regarding participation. Medication used to treat behaviour that challenges will be reviewed by the pharmacist, in collaboration with the general practitioner (GP), person with dementia and carer. The behavioural intervention consists of a training package for care home staff and GPs promoting person-centred care and treating behaviours that challenge as an expression of unmet need. The primary outcome measure is the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Other outcomes include quality of life (EQ-5D and DEMQoL), cognition (sMMSE), health economic (CSRI) and prescribed medication including whether recommendations were implemented. Outcome data will be collected at 6 weeks, and 3 and 6 months. Pretraining and post-training interviews will explore stakeholders’ expectations and experiences of the intervention. Data will be used to estimate the sample size for a definitive study.

Ethics/dissemination

The project has received a favourable opinion from the East Midlands REC (15/EM/3014). If potential participants lack capacity, a personal consultee will be consulted regarding participation in line with the Mental Capacity Act. Results will be published in peer-reviewed journals and presented at conferences.
How much sugar is hidden in drinks marketed to children? A survey of fruit juices, juice drinks and smoothies
Authors: Boulton Jane , Hashem Kawther M , Jenner Katharine H , Lloyd-Williams Ffion , Bromley Helen , Capewell Simon
Published: March 2016

Objective

To investigate the amount of sugars in fruit juices, juice drinks and smoothies (FJJDS) marketed to children.

Design

We surveyed the sugars content (per 100 ml and standardised 200 ml portion) of all FJJDS sold by seven major UK supermarkets (supermarket own and branded products). Only products specifically marketed towards children were included. We excluded sports drinks, iced teas, sugar-sweetened carbonated drinks and cordials as being not specifically marketed towards children.

Results

We identified 203 fruit juices (n=21), juice drinks (n=158) and smoothies (n=24) marketed to children. Sugars content ranged from 0 to 16 g/100 ml. The mean sugars content was 7.0 g/100 ml, but among the 100% fruit juice category, it was 10.7 g/100 ml. Smoothies (13.0 g/100 ml) contained the highest amounts of sugars and juice drinks (5.6 g/100 ml) contained the lowest amount. 117 of the 203 FJJDS surveyed would receive a Food Standards Agency ‘red’ colour-coded label for sugars per standardised 200 ml serving. Only 63 FJJDS would receive a ‘green’ colour-coded label. 85 products contained at least 19 g of sugars—a child's entire maximum daily amount of sugars. 57 products contained sugar (sucrose), 65 contained non-caloric sweeteners and five contained both. Seven products contained glucose-fructose syrup.

Conclusions

The sugars content in FJJDS marketed to children in the UK is unacceptably high. Manufacturers must stop adding unnecessary sugars and calories to their FJJDS.
Analysis of solid waste management systems in Alberta and British Columbia using provincial comparison
Authors: Bruce Nathan , Asha Aklima Zerin , Ng Kelvin Tsun Wai
Published: March 2016

In this paper, waste management in Alberta (AB) and British Columbia (BC) from 1996 to 2010 are examined with respect to generation characteristics and management efficiency. The daily average waste generation rates in AB and BC were 3.34 kg/capita and 2.50 kg/capita, respectively. It was found that annual family income has a positive relation with residential waste generation in both provinces, as did the proportion of educated citizens. Gross domestic product was positively related to non-residential waste generation in AB, and negatively related in BC. Annual agricultural farm cash receipts were positively related to non-residential waste generation in both provinces, and AB’s industry earnings were significantly higher. Between 1998 and 2010, the average diversion rate in AB was 15.1%, and BC’s was 32.9%, which place them on opposing sides of the national average (23.4%). Total operating expenditures were similar in both provinces, yet BC’s waste diversion was more than double AB’s.
Nongrowing season soil surface nitrate and phosphate dynamics in a corn–soybean rotation in eastern Canada: in situ evaluation using anionic exchange membranes
Authors: Shi Yichao , Ziadi Noura , Messiga Aimé J. , Lalande Roger
Published: March 2016

Determining how agricultural management practices affect changes in soil nitrogen (N) and phosphorus (P) could further our understanding of soil N and P cycle. The main objective of this study was to assess in situ nongrowing season soil nitrate and phosphate dynamics as adsorbed on anionic exchange membranes (AEM-N and AEM-P, respectively). The membranes were buried in the surface horizon (5 cm below the soil surface) over the nongrowing season (mid-November to mid-April) in five consecutive years (2009–2010 to 2013–2014) in a long-term corn–soybean rotation experiment established in 1992 in eastern Canada. The treatments consisted of two tillage systems, namely moldboard plow (MP) and no-till (NT), and nine combinations of fertilizer applications, namely three N rates (0, 80, and 160 kg N ha−1) and three P rates (0, 17.5, and 35 kg P ha−1) in a split-plot design with four replications. The results showed that AEM-N and AEM-P averaged 1.8 µg cm−2 d−1 and 7.4 ng cm−2 d−1 under MP, respectively, and 2.8 µg cm−2 d−1 and 67.8 ng cm−2 d−1 under NT, respectively. Nitrogen application increased AEM-N in 2010–2011, 2011–2012, and 2012–2013, but decreased AEM-P mainly under NT. Phosphorus fertilization had no effect on AEM-N, but increased AEM-P under both MP and NT. We conclude that AEM can be used as a technique to study N and P dynamics under cold winters of eastern Canada.
Applicability of second-order expansion in s13 to explore δCP in small and medium baseline ν experiments
Authors: Singh Mandip
Published: March 2016

The series expansion of neutrino evolution matrix “[Formula: see text]”, up to first-order in small reactor mixing angle [Formula: see text] is very useful formalism to study experiments quantitatively. The formalism has been used especially to investigate CP-violating phase [Formula: see text]. In order to perform a broad investigation for the possible measurement of [Formula: see text] phase, we will study small baseline experiments: Chooz [Formula: see text], T2K [Formula: see text] and ESS [Formula: see text], medium baseline experiment: NO[Formula: see text]A [Formula: see text] and long baseline experiment: LBNE [Formula: see text].
Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease
Authors: Nie Di-min , Wu Qiu-ling , Zheng Peng , Chen Ping , Zhang Ran , Li Bei-bei , Fang Jun , Xia Ling-hui , Hong Mei
Published: March 2016

Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD.
Twelve hours of heat stress induces inflammatory signaling in porcine skeletal muscle
Authors: Ganesan Shanthi , Reynolds Carmen , Hollinger Katrin , Pearce Sarah C. , Gabler Nicholas K. , Baumgard Lance H. , Rhoads Robert P. , Selsby Joshua T.
Published: March 2016

Heat stress causes morbidity and mortality in humans and animals and threatens food security by limiting livestock productivity. Inflammatory signaling may contribute to heat stress-mediated skeletal muscle dysfunction. Previously, we discovered increased circulating endotoxin and intramuscular oxidative stress and TNF-α protein abundance, but not inflammatory signaling following 24 and 72 h of heat stress. Thus the purpose of this investigation was to clarify the role of inflammatory signaling in heat-stressed skeletal muscle. Crossbred gilts ( n = 8/group) were assigned to either thermal neutral (24°C), heat stress (37°C), or pair-fed thermal neutral (24°C) conditions for 12 h. Following treatment, animals were euthanized, and the semitendinosus red (STR) and white (STW) were recovered. Heat stress did not alter inflammatory signaling in STW. In STR, relative heat shock protein abundance was similar between groups, as was nuclear content of heat shock factor 1. In whole homogenate, relative abundance of the NF-κB activator inhibitory κB kinase-α was increased by heat stress, although abundance of NF-κB was similar between groups. Relative abundance of phosphorylated NF-κB was increased by heat stress in nuclear fractions. Activator protein-1 (AP-1) signaling was similar between groups. While there were few differences in transcript expression between thermal neutral and heat stress, 80 and 56% of measured transcripts driven by NF-κB or AP-1, respectively, were increased by heat stress compared with pair-fed thermal neutral. Heat stress also caused a reduction in IL-6 transcript and relative protein abundance. These data demonstrate that short-term heat stress causes inflammatory signaling through NF-κB in oxidative, but not glycolytic, skeletal muscle.
Decreased otolith-mediated vestibular response in 25 astronauts induced by long-duration spaceflight
Authors: Hallgren Emma , Kornilova Ludmila , Fransen Erik , Glukhikh Dmitrii , Moore Steven T. , Clément Gilles , Van Ombergen Angelique , MacDougall Hamish , Naumov Ivan , Wuyts Floris L.
Published: March 2016

The information coming from the vestibular otolith organs is important for the brain when reflexively making appropriate visual and spinal corrections to maintain balance. Symptoms related to failed balance control and navigation are commonly observed in astronauts returning from space. To investigate the effect of microgravity exposure on the otoliths, we studied the otolith-mediated responses elicited by centrifugation in a group of 25 astronauts before and after 6 mo of spaceflight. Ocular counterrolling (OCR) is an otolith-driven reflex that is sensitive to head tilt with regard to gravity and tilts of the gravito-inertial acceleration vector during centrifugation. When comparing pre- and postflight OCR, we found a statistically significant decrease of the OCR response upon return. Nine days after return, the OCR was back at preflight level, indicating a full recovery. Our large study sample allows for more general physiological conclusions about the effect of prolonged microgravity on the otolith system. A deconditioned otolith system is thought to be the cause of several of the negative effects seen in returning astronauts, such as spatial disorientation and orthostatic intolerance. This knowledge should be taken into account for future long-term space missions.
Distinct α- and β-band rhythms over rat somatosensory cortex with similar properties as in humans
Authors: Fransen Anne M. M. , Dimitriadis George , van Ede Freek , Maris Eric
Published: March 2016

We demonstrate distinct α- (7–14 Hz) and β-band (15–30 Hz) rhythms in rat somatosensory cortex in vivo using epidural electrocorticography recordings. Moreover, we show in rats that a genuine β-rhythm coexists alongside β-activity that reflects the second harmonic of the arch-shaped somatosensory α-rhythm. This demonstration of a genuine somatosensory β-rhythm depends on a novel quantification of neuronal oscillations that is based on their rhythmic nature: lagged coherence. Using lagged coherence, we provide two lines of evidence that this somatosensory β-rhythm is distinct from the second harmonic of the arch-shaped α-rhythm. The first is based on the rhythms' spatial properties: the α- and β-rhythms are demonstrated to have significantly different topographies. The second is based on the rhythms' temporal properties: the lagged phase-phase coupling between the α- and β-rhythms is demonstrated to be significantly less than would be expected if both reflected a single underlying nonsinusoidal rhythm. Finally, we demonstrate that 1) the lagged coherence spectrum is consistent between signals from rat and human somatosensory cortex; and 2) a tactile stimulus has the same effect on the somatosensory α- and β-rhythms in both rats and humans, namely suppressing them. Thus we not only provide evidence for the existence of genuine α- and β-rhythms in rat somatosensory cortex, but also for their homology to the primate sensorimotor α- and β-rhythms.
Altered intrinsic connectivity of the auditory cortex in congenital amusia
Authors: Leveque Yohana , Fauvel Baptiste , Groussard Mathilde , Caclin Anne , Albouy Philippe , Platel Hervé , Tillmann Barbara
Published: March 2016

Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest.
Inflammatory stimuli acutely modulate peripheral taste function
Authors: Kumarhia Devaki , He Lianying , McCluskey Lynnette Phillips
Published: March 2016

Inflammation-mediated changes in taste perception can affect health outcomes in patients, but little is known about the underlying mechanisms. In the present work, we hypothesized that proinflammatory cytokines directly modulate Na+ transport in taste buds. To test this, we measured acute changes in Na+ flux in polarized fungiform taste buds loaded with a Na+ indicator dye. IL-1β elicited an amiloride-sensitive increase in Na+ transport in taste buds. In contrast, TNF-α dramatically and reversibly decreased Na+ flux in polarized taste buds via amiloride-sensitive and amiloride-insensitive Na+ transport systems. The speed and partial amiloride sensitivity of these changes in Na+ flux indicate that IL-1β and TNF-α modulate epithelial Na+ channel (ENaC) function. A portion of the TNF-mediated decrease in Na+ flux is also blocked by the TRPV1 antagonist capsazepine, although TNF-α further reduced Na+ transport independently of both amiloride and capsazepine. We also assessed taste function in vivo in a model of infection and inflammation that elevates these and additional cytokines. In rats administered systemic lipopolysaccharide (LPS), CT responses to Na+ were significantly elevated between 1 and 2 h after LPS treatment. Low, normally preferred concentrations of NaCl and sodium acetate elicited high response magnitudes. Consistent with this outcome, codelivery of IL-1β and TNF-α enhanced Na+ flux in polarized taste buds. These results demonstrate that inflammation elicits swift changes in Na+ taste function, which may limit salt consumption during illness.
The Relevance of Apoptosis for Cellular Homeostasis and Tumorogenesis in the Intestine
Authors: Renehan Andrew G , Bach Simon P , Potten Christopher S
Published: March 2016

Intestinal epithelium is a rapidly renewing tissue in which cell homeostasis is regulated by a balance among proliferation, growth arrest, differentiation and apoptosis (programmed cell death). Until recently, studies on oncogenesis have focused on the regulation of cell proliferation. The recognition that apoptosis must be understood to comprehend how appropriate cell numbers are maintained and how alterations in any part of the equation can contribute to malignancy has led to an explosion of research in this field. The first half of this review gives an overview of morphology and mechanisms of apoptosis, emphasizing key areas of genetic control such as thebcl-2family andp53. The second half of the review focuses on the role of apoptosis in normal cellular homeostasis and tumorigenesis in the gastrointestinal epithelium. The importance of understanding the molecular biology of apoptotic pathways in cancer therapy and future directions are also addressed.
Reactivation of Hepatitis B e Antigen-Negative Chronic Hepatitis B in a Bone Marrow Transplant Recipient following Lamivudine Withdrawal
Authors: Myers Robert P , Swain Mark G , Urbanski Stefan J , Lee Samuel S
Published: March 2016

Reactivation of hepatitis B virus (HBV) is a recognized complication of bone marrow transplantation (BMT). Lamivudine is a nucleoside analogue with potent antiviral activity that has been used in the prophylaxis of HBV reactivation in at-risk BMT recipients. Currently, no data exist regarding the safety of nucleoside analogue withdrawal in these patients. A 32-year-old BMT recipient with hepatitis B e antigen (HBeAg)-negative, chronic HBV who developed a serious flare of hepatic inflammation due to a rebound in viral replication within 12 weeks of discontinuing lamivudine therapy is described. The patient remained HBeAg-negative despite high level viremia, suggesting the emergence of a mutant viral strain. The patient's acute hepatitis resolved promptly with the reinstitution of lamivudine therapy. Further studies are necessary to define the safety and efficacy of nucleoside analogues in the prevention of HBV reactivation in at-risk BMT recipients. Clinicians should consider the risk of inducing serious flares of hepatic inflammation due to abrupt nucleoside analogue withdrawal in these patients.
Crohn's Disease of the Esophagus: Three Cases and a Literature Review
Authors: Rudolph Ivan , Goldstein Franz , DiMarino Anthony J
Published: March 2016

Three cases of esophageal Crohn's disease (CD) are described, each with dysphagia and/or odynophagia caused by esophageal ulceration. All three patients had associated ileocolitis. One patient followed for a prolonged period responded to treatment with sulfasalazine and prednisone. A computer search back to 1967 produced 72 additional cases of esophageal CD. Among these 75 patients (total), who were, on average, 34 years old, esophageal disease was the presenting disease symptom in 41 patients (55%). The diagnosis was difficult in 13 patients, in whom no distal bowel disease was detected at the time of initial esophageal presentation. The most common presentation was dysphagia associated with aphthous or deeper ulcerations (52 patients). In 11 of these patients, oral aphthous ulcerations were also present. Esophageal stenosis or fistulas to surrounding structures were present in 27 patients and led to surgery in 17 patients. Most of the unfavourable outcomes were in this group of 27 patients with esophageal complications, including five deaths. Fourteen additional patients required surgery for CD of other areas. Responses of uncomplicated ulcerative disease of the esophagus tended to be favourable if the medical regimen included prednisone. Clinical patterns of esophageal CD were divided into three categories: ulcerative, stenosing and asymptomatic (acute disease in children).
Anti-TNF Therapy and Malignancy – A Critical Review
Authors: Cohen Roger B , Dittrich Karen A
Published: March 2016

The roles of tumour necrosis factor (TNF) and anti-TNF therapy in malignancy are reviewed, including an overview of baseline risk factors for malignancy in inflammatory diseases and the incidences of malignancies observed in clinical trials of an anti-TNF-a therapy, infliximab. The preclinical data and early clinical experience presented for infliximab do not provide evidence for a causal relationship between TNF-a antagonism and the development of lymphoid or nonlymphoid cancers.
Application of the Vienna Classificaton for Crohn's Disease to a Single Clinician Database of 877 Patients
Authors: Freeman Hugh James
Published: March 2016

An international working party at the World Congress of Gastroenterology held in Vienna, Austria from September 6 to 11, 1998 defined a classification for Crohn's disease based on patient age at diagnosis (eg, less than 40 years of age, 40 years of age or older), disease location (eg, terminal ileum, colon, ileocolon or upper gastrointestinal tract) and behaviour (eg, stricturing, penetrating). Disease location in the upper gastrointestinal tract was defined by disease being present proximal to the terminal ileum, regardless of terminal ileal or colon involvement. A 20-year, single clinician database of 877 patients from a university campus hospital was used, and comprised 492 women (56.1%) and 385 men (43.9%). Of these patients, 740 (84.4%) were diagnosed before age 40 years and 137 (15.6%) were diagnosed by 40 years of age or older. Disease was located in the terminal ileum alone in 222 patients (25.3%), colon alone in 238 patients (27.2%) and ileocolon in 304 patients (34.6%). Another 113 patients (13.1%) had disease in the upper gastrointestinal tract, usually with disease also in the terminal ileum (23 patients), colon (12 patients) or ileocolon (71 patients). Only seven of 877 patients had disease located in the upper gastrointestinal tract alone with no distal disease. Disease behaviour could be classified as nonstricturing and nonpenetrating in 256 patients (29.2%), stricturing in 294 patients (33.6%) and penetrating in 327 patients (37.2%). Of the 877 patients with Crohn's disease, 837 were white, 38 were Asian and two were black. In this tertiary care setting of a single clinician practice in a Canadian teaching hospital at the University of British Columbia, Crohn's disease predominantly affects women, and young adults with a high rate of stricturing and penetrating complications.
Dysplasia-Associated Polypoid Mucosal Lesion in a Pelvic Pouch after Restorative Proctocolectomy for Ulcerative Colitis
Authors: Freeman Hugh
Published: March 2016

A 32-year-old man with ulcerative colitis had a colectomy for toxic colitis. Later, a rectal mucosectomy was performed along with the creation of a pelvic pouch. In 1998, approximately 10 years after this staged restorative proctocolectomy was completed, endoscopic examination of the pelvic pouch detected a small mucosal polypoid mass lesion. Although the lesion had the macroscopic appearance of an inflammatory polyp, microscopic sections of the resected lesion revealed dysplastic changes. Endoscopic polypectomy was performed to remove the lesion, and further histological surveillance examinations of the pelvic pouch have not detected additional dysplastic mucosal changes.
The Dyspepsia Alphabet: DU, GU, GERD, NERD, NUD/FD and UD
Authors: Thomson ABR
Published: March 2016

The care of patients with dyspepsia may be almost as confusing as the many terms that are used to describe this very common symptom. A symptom-based approach may prove to be ideal for the patient with undiagnosed dyspepsia. This brief overview describes some of the many terms used to describe dyspepsia. Clearly, new treatment algorithms are needed for the care of patients with undiagnosed dyspepsia seen in a primary care setting.
Granulomatous Cheilitis and Crohn's Disease
Authors: Ahmad Ishfaq , Owens David
Published: March 2016

Granulomatous cheilitis is characterized by recurrent swelling of the labial tissues and granulomatous histology. Granulomatous cheilitis has been recognized as an early manifestation of Crohn's disease. It may follow, coincide with or precede the onset of Crohn's disease. The first case presented involved an extraintestinal manifestation of Crohn's disease, and the second case presented is of development of granulomatous cheilitis a year before the onset of symptomatic Crohn's disease. Although chronic granulomatous cheilitis is a very rare disorder, once it is diagnosed, the patient should be followed up carefully. These patients should be investigated for asymptomatic Crohn's disease either when the diagnosis of granulomatous cheilitis is confirmed or when gastrointestinal symptoms develop.
Pancreatitis with Electrocardiographic Changes Mimicking Acute Myocardial Infarction
Authors: Khairy Paul , Marsolais Pierre
Published: March 2016

A 64‐year‐old woman with mild acute pancreatitis presented with epigastric pain, nausea and vomiting while undergoing hemodialysis for chronic renal insufficiency. Serial electrocardiograms revealed new onset ST segment elevations in leads V2 to V4 mimicking an anterior myocardial infarction, followed by diffusely inverted deep T waves. No cardiac pathology was demonstrated by echocardiography or coronary angiography. A review of the literature and possible pathophysiological mechanisms of electrocardiographic changes in acute pancreatitis, such as metabolic abnormalities, hemodynamic instability, vasopressors, pericarditis, myocarditis, a cardiobiliary reflex, exacerbation of underlying cardiac pathology, coagulopathy and coronary vasospasm, are discussed.
Gastroparesis: Prevalence, Clinical Significance and Treatment
Authors: Horowitz Michael , Su Yu-Chung , Rayner Christopher K , Jones Karen L
Published: March 2016

The application of novel techniques to quantify gastric motor function and gastric emptying has yielded important insights into the prevalence, pathogenesis and clinical sequelae of gastroparesis. Both acute and chronic gastroparesis occur frequently; gastric emptying of solids is delayed in 30% to 50% of patients with diabetes mellitus, functional dyspepsia and gastroesophageal reflux disease. While many patients with gastroparesis experience upper gastrointestinal symptoms that adversely affect quality of life, the concept that symptoms are inevitably the direct outcome of delay in gastric emptying is now recognized to be overly simplistic. In contrast, the potential impact of gastroparesis on oral drug absorption and blood glucose control in patients with diabetes mellitus has probably been underestimated. While the use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy in symptomatic patients with gastroparesis, a number of novel pharmacological therapies are being evaluated, and preliminary studies using gastric pacing show promise.
High Prevalence of Celiac Disease in Patients with Type 1 Diabetes Detected by Antibodies to Endomysium and Tissue Transglutaminase
Authors: Gillett PM , Gillett HR , Israel DM , Metzger DL , Stewart L , Chanoine J-P , Freeman HJ
Published: March 2016

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia.

PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed.

RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy.

CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.
Dysplasia Risk in Ileal Pouches after Reconstructive Surgery for Ulcerative Colitis
Authors: Freeman Hugh J
Published: March 2016

An important goal for the surgeon after performing proctocolectomy for ulcerative colitis is the preservation of continence, with the formation of a pelvic ileal pouch. In most patients who have required this procedure, clinical results have been satisfactory. In recent years, it has become appreciated that many patients with a satisfactory surgical result are still at risk for pouchitis and pouch neoplasia. This is not surprising because creation of a pouch leads to an environment characterized by stasis, with associated mucosal adaptive changes. In some patients, the ileal mucosa in the pouch may assume the appearance of colonic mucosa.
Colonic Disorders in Adult Cystic Fibrosis
Authors: Chaun Hugh
Published: March 2016

By 1996, the median survival of patients with cystic fibrosis (CF) in North America had increased to 31 years. With the markedly improved life expectancy, many CF patients are now adults. There is an associated increased risk of certain colonic disorders, and the emergence of other previously unrecognized disorders, in adult CF patients. The distal intestinal obstruction syndrome (DIOS), which is more common in older patients, is a frequent cause of abdominal pain. Intussusception may complicate DIOS; other differential diagnoses include appendiceal disease, volvolus, Crohn's disease, fibrosing colonopathy and colonic carcinoma. The diagnosis of acute appendicitis, although uncommon in patients with CF, is often delayed, and appendiceal abscess is a frequent complication. The prevalence of Crohn's disease in CF has been shown to be 17 times that of the general population. Right-sided microscopic colitis is a recently recognized entity in CF of uncertain clinical significance. Fibrosing colonopathy has been confined mostly to children with CF, attributed to the use of high strength pancreatic enzyme supplements, but it has been reported in three adults. Nine cases of carcinoma of the large intestine have been reported worldwide, associated with an apparent excess risk of digestive tract cancers in CF. Despite high carrier rates ofClostridium difficilein patients with CF, pseudomembranous colitis is distinctly rare, but severe cases complicated by toxic megacolon have been reported. In these patients, watery diarrhea is often absent. Adult CF patients with refractory or unexplained intestinal symptoms merit thorough investigations.
Cytokines and Liver Diseases
Authors: Tilg Herbert
Published: March 2016

Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a) has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.
An Unusual Case of Hepatic Abscess
Authors: Tambay Robert , Côté Jean , Bourgault Anne-Marie , Villeneuve Jean-Pierre
Published: March 2016

A case of recurring primary hepatic actinomycosis is reported. A 50-year-old man presented with fever, weight loss and multiple hepatic masses. A diagnosis was obtained by cytological examination of a biopsy sample taken from the largest hepatic mass, which revealed the presence ofActinomycesspecies. The patient was treated with penicillin for 12 months and did well. Seven years later, he presented with similar symptoms but with a single large liver mass and a pulmonary infiltrate in the right lower lobe. Liver biopsy showed an inflammatory pseudotumour, and lung biopsy showed the presence ofActinomycesspecies. Again, the patient was treated with penicillin. Five months later, the patient was doing well, and a follow-up computed tomography scan showed partial regression of the hepatic pseudotumour. This case indicates that hepatic actinomycosis can recur several years after an appropriate treatment and stresses the need for careful follow-up in such patients.
Intestinal Carcinoid Tumours in a Father and Daughter
Authors: Pal Tuya , Liede Alexander , Mitchell Margot , Calender Alain , Narod Steven A
Published: March 2016

Familial cases of carcinoid tumours that are not associated with any known syndrome or disease are extremely rare. All cases reported in the world literature have involved carcinoid tumours of the gastrointestinal tract. Two cases of carcinoid tumours of the small intestine in a father and daughter are presented. Laboratory analyses did not support the hypothesis that the occurrence of carcinoid tumours in this family is a variant of the multiple endocrine neoplasia type 1 syndrome. A review of the literature on familial occurrence of intestinal carcinoid tumours in the absence of any other known carcinoid tumour-predisposing genetic syndrome is provided.
Stability of Human Gallbladder Bile: Effect of Freezing
Authors: Janowitz Paul , Mason Richard , Kratzer Wolfgang
Published: March 2016

In the present study, the stability of the most essential biliary parameters of human gallbladder bile at -18°C was examined over several months. In 12 patients with gallstone disease (10 female, two male; 52.1±13.3 years of age), bile was obtained through fine needle puncture of the gallbladder under local anesthetic. The concentrations of total lipids, cholesterol, phospholipids and bile acids, and the cholesterol saturation index and crystal appearance time were determined before and after freezing over a mean period of 4.38±2.9 months. Gallbladder bile obtained by fine needle puncture has proved to be of excellent quality. The total lipid concentration was unchanged before (8.30±4.16 g/dL) and after freezing (9.16±4.54 g/dL, P=0.6027). The biliary cholesterol, phospholipids and bile acid concentrations, and cholesterol saturation index showed no statistically significant differences before and after freezing. A significant difference arises in the context of subdivision of the group to the nucleation time. Before freezing, most patients had a nucleation time between five and eight days, which shortened to between one and four days after thawing (P=0.0100). The authors conclude that, with the exception of the nucleation time, human gallbladder bile can be stored at -18°C for four months with stability of major lipid components.
From the Gut to the Liver: Another Organ to Watch in FAP Patients
Authors: Paulson Spencer , Patel Charmi , Patel Hitendra
Published: March 2016

We report a rare association of hepatocellular carcinoma with familial adenomatous polyposis in a young patient and its clinical significance. A 28-year-old female with a past medical history of familial adenomatous polyposis (FAP) and subsequent colonic adenocarcinoma underwent total colectomy. She later presented with intermittent right upper quadrant pain and nausea of four months’ duration. MRI of the abdomen revealed multiple liver lesions, the largest 8.5 cm in diameter, with radiologic features suggestive of hepatocellular carcinoma. A CT-guided liver biopsy demonstrated well-differentiated HCC which was confirmed by immunohistochemistry. In patients with a history of FAP, a heightened awareness of the possibility of concurrent or subsequent HCC is warranted.
Multiobjective Design of Wearable Sensor Systems for Electrocardiogram Monitoring
Authors: Martinez-Tabares F. J. , Costa-Salas Y. J. , Cuesta-Frau D. , Castellanos-Dominguez G.
Published: March 2016

Wearable sensor systems will soon become part of the available medical tools for remote and long term physiological monitoring. However, the set of variables involved in the performance of these systems are usually antagonistic, and therefore the design of usable wearable systems in real clinical applications entails a number of challenges that have to be addressed first. This paper describes a method to optimise the design of these systems for the specific application of cardiac monitoring. The method proposed is based on the selection of a subset of 5 design variables, sensor contact, location, and rotation, signal correlation, and patient comfort, and 2 objective functions, functionality and wearability. These variables are optimised using linear and nonlinear models to maximise those objective functions simultaneously. The methodology described and the results achieved demonstrate that it is possible to find an optimal solution and therefore overcome most of the design barriers that prevent wearable sensor systems from being used in normal clinical practice.