bluuebunny/crossref_metadata_2025 huggingface dataset:
Illustration of informal caregiving within Saudi society: demography, scope of care and enabling arrangements
Authors: Alrashed Abeer M.
Published: April 2016

Although informal caregiving is a vital element in the process of supporting individuals with dependency, it is unrecognised most of the time, particularly by caregivers themselves. In Saudi Arabia, little attention has been devoted to informal caregivers; therefore, scarce coverage of this topic is obvious within the literature. This descriptive cross‐sectional study was carried to explore informal caregiving within Saudi society by (i) describing informal caregivers and their care recipients and (ii) measuring the scope of care and enabling arrangements in the lives of informal caregivers. Numerical measures of frequency distribution were used to describe the participants and the correlate of demography among 341 female primary caregivers of the elderly (40%), individuals with disabilities (10%) or/and children aged five or younger (51%). Inferential statistics were used to test for significant associations among study variables. The majority of the participants were married with children and were middle‐aged. However, the majority of care recipients were living with their caregivers; in addition, they were primarily females cared for by a mother or, less often, by a daughter (in‐law). Enabling arrangements were on a moderate level, mainly in healthcare access, financial resources and family support, with lower signs detected in the quality of sleep indicator. These arrangements were significantly associated with caregiver age, education, career status and source of assistance. In conclusion, the statistics revealed by this survey indicated certain challenges that have been encountered by informal caregivers, primarily involving financial and social support. More coverage within the formal system of childcare must be provided to facilitate healthier childhoods. The long‐term needs of individuals with dependency must be considered in the planning process of healthcare services, as well, remembering the needs and expectations of informal caregivers.
EFFECT OF BOLUS SIZE ON DEGLUTITION AND ESOPHAGEAL TRANSIT IN HEALTHY DOGS
Authors: Cheney Diane M. , Marks Stanley L. , Pollard Rachel E.
Published: April 2016

Contrast videofluoroscopy is the gold standard procedure for evaluating dysphagia in humans, but quantitative measures vary depending on bolus size and consistency. We hypothesized that quantitative measures made during videofluoroscopy of swallowing in dogs would differ between bolus sizes and consistencies. Ten healthy adult dogs were enrolled a prospective, crossover experimental study and underwent contrast videofluoroscopy while swallowing liquid (5, 10, and 15 ml) and canned food (3, 8, and 12 g) boluses. Maximum pharyngeal contraction occurred significantly later with medium solid boluses than with medium liquid boluses, with a mean difference of 0.021 s (adjusted P = 0.042). Upper esophageal sphincter opening occurred significantly earlier with large solid boluses than with medium solid boluses, with a mean difference of 0.018 s (adjusted P = 0.025). Thoracic esophageal transit time was significantly longer with small solid boluses than with small liquid boluses, with a mean difference of 0.68 s (adjusted P = 0.004). Odds of primary esophageal peristalsis occurring were significantly (18.5 times) higher with large solid vs. large liquid boluses (adjusted P = 0.031). No other statistical comparisons reached significance. Based on these results, we recommend a standardized approach to videofluoscopy in dogs with determination of quantitative measures using medium liquid and soft food boluses to minimize effects of size. Furthermore, we conclude that measurements made on liquid swallows should not be directly compared to measurements made on soft food boluses.
Leisure-Time Physical Activity: Experiences of College Students With Disabilities
Authors: Devine Mary Ann
Published: April 2016

College years are an experimental phase in young adulthood and can lay the foundation for lifelong behaviors. One type of behavior developed during these years is the use of leisure-time physical activity (LTPA). LTPA experiences of typical college students have been examined, but there is a lack of studies examining the experiences of students with disabilities. The purpose of this inquiry is to understand the experiences of college students with disabilities and their LTPA, with focus on factors that facilitate or create barriers to engagement. Grounded theory was used to understand LTPA with undergraduates with mobility or visual impairments. Results indicated a theme of culture of physical activity and disability as they received a message that engagement in LTPA was “unnecessary” or “heroic,” which altered their LTPA experiences. Barriers to LTPA can be understood through a social relational lens to recognize the multidimensionality of barriers and facilitators to LTPA.
Obsolescence looms for balloon data
Authors: Hand Eric
Published: April 2016

United States falls behind Europe in adopting modern data format.
The savior cells?
Authors: Couzin-Frankel Jennifer
Published: April 2016

After a painstaking journey, researchers are preparing to test stem cell therapy in ailing fetuses.
Magnetic remanence in single atoms
Authors: Donati F. , Rusponi S. , Stepanow S. , Wäckerlin C. , Singha A. , Persichetti L. , Baltic R. , Diller K. , Patthey F. , Fernandes E. , Dreiser J. , Šljivančanin Ž. , Kummer K. , Nistor C. , Gambardella P. , Brune H.
Published: April 2016

Stable magnets from single atoms

An important goal in molecular magnetism is to create a permanent magnet from a single atom. Metal atoms adsorbed on surfaces can develop strong magnetization in an applied field (paramagnetism). Donati
et al.
show that single holmium atoms adsorbed on a magnesium oxide film grown on a silver substrate show residual magnetism for temperatures up to 30 K and bistabilty that lasts for 1500 s at 10 K (see the Perspective by Khajetoorians and Heinrich). The atom avoids spin relaxation by a combination of quantum-state symmetry and by the oxide film preventing the spin from interacting with the underlying metal via tunneling.

Science
, this issue p.
318
; see also p.
296
Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens
Authors: Toliman P. , Badman S. G. , Gabuzzi J. , Silim S. , Forereme L. , Kumbia A. , Kombuk B. , Kombati Z. , Allan J. , Munnull G. , Ryan C. , Vallely L. M. , Kelly-Hanku A. , Wand H. , Mola G. D. L. , Guy R. , Siba P. , Kaldor J. M. , Tabrizi S. N. , Vallely A. J.
Published: April 2016

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.
Quantitative Assessment of Commutability for Clinical Viral Load Testing Using a Digital PCR-Based Reference Standard
Authors: Tang L. , Sun Y. , Buelow D. , Gu Z. , Caliendo A. M. , Pounds S. , Hayden R. T.
Published: April 2016

Given recent advances in the development of quantitative standards, particularly WHO international standards, efforts to better understand the commutability of reference materials have been made. Existing approaches in evaluating commutability include prediction intervals and correspondence analysis; however, the results obtained from existing approaches may be ambiguous. We have developed a “deviation-from-ideal” (DFI) approach to evaluate commutability of standards and applied it to the assessment of Epstein-Bar virus (EBV) load testing in four quantitative PCR assays, treating digital PCR as a reference assay. We then discuss advantages and limitations of the DFI approach as well as experimental design to best evaluate the commutability of an assay in practice.
Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74
Authors: Saito Akatsuki , Ferhadian Damien , Sowd Gregory A. , Serrao Erik , Shi Jiong , Halambage Upul D. , Teng Samantha , Soto Juan , Siddiqui Mohammad Adnan , Engelman Alan N. , Aiken Christopher , Yamashita Masahiro
Published: April 2016

The viral capsid of HIV-1 interacts with a number of host factors to orchestrate uncoating and regulate downstream events, such as reverse transcription, nuclear entry, and integration site targeting. PF-3450074 (PF74), an HIV-1 capsid-targeting low-molecular-weight antiviral compound, directly binds to the capsid (CA) protein at a site also utilized by host cell proteins CPSF6 and NUP153. Here, we found that the dose-response curve of PF74 is triphasic, consisting of a plateau and two inhibitory phases of different slope values, consistent with a bimodal mechanism of drug action. High PF74 concentrations yielded a steep curve with the highest slope value among different classes of known antiretrovirals, suggesting a dose-dependent, cooperative mechanism of action. CA interactions with both CPSF6 and cyclophilin A (CypA) were essential for the unique dose-response curve. A shift of the steep curve at lower drug concentrations upon blocking the CA-CypA interaction suggests a protective role for CypA against high concentrations of PF74. These findings, highlighting the unique characteristics of PF74, provide a model in which its multimodal mechanism of action of both noncooperative and cooperative inhibition by PF74 is regulated by interactions of cellular proteins with incoming viral capsids.

IMPORTANCE
PF74, a novel capsid-targeting antiviral against HIV-1, shares its binding site in the viral capsid protein (CA) with the host factors CPSF6 and NUP153. This work reveals that the dose-response curve of PF74 consists of two distinct inhibitory phases that are differentially regulated by CA-interacting host proteins. PF74's potency depended on these CA-binding factors at low doses. In contrast, the antiviral activity of high PF74 concentrations was attenuated by cyclophilin A. These observations provide novel insights into both the mechanism of action of PF74 and the roles of host factors during the early steps of HIV-1 infection.
CT head imaging in patients with head injury who present after 24 h of injury: a retrospective cohort study
Authors: Marincowitz Carl , Allgar Victoria , Townend William
Published: April 2016

Background

National Institute for Health and Care Excellence guidelines used to triage patients with head injury to CT imaging are based on research conducted in populations presenting within 24 h of injury.

We aim to compare guideline use, and outcomes, in patients with head injury that undergo CT imaging presenting within, and after 24 h of injury.

Methods

ED trauma CT head scan requests over a period of 6 months were matched to ED records. Case note review of adult patients with head injury that had undergone CT imaging was completed. Logistic regression was used to assess whether presentation after 24 h affected the guideline's ability to predict significant injuries.

Results

650 case records were available for analysis. 8.6% (56/650) showed a traumatic abnormality, 1.5% (10/650) required neurosurgery or died. 15.5% (101/650) of CT scans were for patients presenting after 24 h. 8.4% (46/549) of those presenting within, and 9.9% (10/101) of those presenting after 24 h had traumatic CT abnormalities.

The sensitivity of the guidelines for intracranial injuries was 98% (95% CI 87.0% to 99.9%) in those presenting within 24 h and 70% (95% CI 35.4% to 91.9%) in those presenting after 24 h of injury. The presence of a guideline indication statistically predicted significant injury, and this was unaffected by time of presentation.

Conclusions

Patients with head injury presenting after 24 h of injury are a clinically significant population. Existing guidelines appear to predict traumatic CT abnormalities irrespective of timing of presentation. However, their sole use in patients presenting after 24 h may result in significant injuries not being identified.
A quantitative study of cotyledon positioning in conifer development
Authors: Holloway David M. , Brook Byron , Kang JooHyun , Wong Cameron , Wu Michael
Published: April 2016

The number of cotyledons in angiosperm monocots and dicots is tightly constrained. But in the gymnosperm Pinaceae (pine family), which includes many of the conifers, cotyledon number (nc) can vary widely, commonly from 2 to 12. Conifer cotyledons form in whorled rings on a domed embryo geometry. We measured the diameter of embryos and counted the cotyledons to determine the radial positioning of the whorl and the circumferential spacing between cotyledons. Results were similar between Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), Sitka spruce (Picea sitchensis (L.) H.Karst.), and larch (Larix × leptoeuropaea, synonymous with L. × marschlinsii Coaz), indicating a common mechanism for cotyledon positioning in conifers. Disrupting transport of the growth regulator auxin (with 1-N-naphthylphthalamic acid (NPA)) led to cup-shaped embryos, indicating that whorl (ring) formation is separable from cotyledon patterning within the ring. NPA inhibits cotyledon outgrowth, but not the spacing (distance) between cotyledons. The NPA effect is direct; it does not operate indirectly on embryo size. These results support a hierarchical model for cotyledon positioning in conifers, in which a first stage (not requiring auxin transport) sets the whorl position, constraining the second stage (which requires auxin transport) to form cotyledons within this whorl. Similarly, recent studies in Arabidopsis have shown that different components of complex developmental patterns can have different transport properties; this aspect of patterning may be shared across plants.
Asphericity of a length four relative group presentation
Authors: Bin Ahmad Abd Ghafur , Al-Mulla Muna A , Edjvet Martin
Published: April 2016

We consider the relative group presentation [Formula: see text], where [Formula: see text] and [Formula: see text]. We show modulo a small number of exceptional cases exactly, when [Formula: see text] is aspherical. If [Formula: see text], then the exceptional cases occur when [Formula: see text] is isomorphic to one of [Formula: see text] or [Formula: see text].
Tumor cell intravasation
Authors: Chiang Serena P. H. , Cabrera Ramon M. , Segall Jeffrey E.
Published: April 2016

The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.
Lithocholic acid attenuates cAMP-dependent Cl− secretion in human colonic epithelial T84 cells
Authors: Ao Mei , Domingue Jada C. , Khan Nabihah , Javed Fatima , Osmani Kashif , Sarathy Jayashree , Rao Mrinalini C.
Published: April 2016

Bile acids (BAs) play a complex role in colonic fluid secretion. We showed that dihydroxy BAs, but not the monohydroxy BA lithocholic acid (LCA), stimulate Cl− secretion in human colonic T84 cells (Ao M, Sarathy J, Domingue J, Alrefai WA, Rao MC. Am J Physiol Cell Physiol 305: C447–C456, 2013). In this study, we explored the effect of LCA on the action of other secretagogues in T84 cells. While LCA (50 μM, 15 min) drastically (>90%) inhibited FSK-stimulated short-circuit current ( Isc), it did not alter carbachol-stimulated Isc. LCA did not alter basal Isc, transepithelial resistance, cell viability, or cytotoxicity. LCA's inhibitory effect was dose dependent, acted faster from the apical membrane, rapid, and not immediately reversible. LCA also prevented the Isc stimulated by the cAMP-dependent secretagogues 8-bromo-cAMP, lubiprostone, or chenodeoxycholic acid (CDCA). The LCA inhibitory effect was BA specific, since CDCA, cholic acid, or taurodeoxycholic acid did not alter FSK or carbachol action. While LCA alone had no effect on intracellular cAMP concentration ([cAMP]i), it decreased FSK-stimulated [cAMP]i by 90%. Although LCA caused a small increase in intracellular Ca2+ concentration ([Ca2+]i), chelation by BAPTA-AM did not reverse LCA's effect on Isc. LCA action does not appear to involve known BA receptors, farnesoid X receptor, vitamin D receptor, muscarinic acetylcholine receptor M3, or bile acid-specific transmembrane G protein-coupled receptor 5. LCA significantly increased ERK1/2 phosphorylation, which was completely abolished by the MEK inhibitor PD-98059. Surprisingly PD-98059 did not reverse LCA's effect on Isc. Finally, although LCA had no effect on basal Isc, nystatin permeabilization studies showed that LCA both stimulates an apical cystic fibrosis transmembrane conductance regulator Cl− current and inhibits a basolateral K+ current. In summary, 50 μM LCA greatly inhibits cAMP-stimulated Cl− secretion, making low doses of LCA of potential therapeutic interest for diarrheal diseases.
Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion
Authors: Paradis Stéphanie , Charles Anne-Laure , Meyer Alain , Lejay Anne , Scholey James W. , Chakfé Nabil , Zoll Joffrey , Geny Bernard
Published: April 2016

Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD.
Fast-adapting mechanoreceptors are important for force control in precision grip but not for sensorimotor memory
Authors: Park Susanna B. , Davare Marco , Falla Marika , Kennedy William R. , Selim Mona M. , Wendelschafer-Crabb Gwen , Koltzenburg Martin
Published: April 2016

Sensory feedback from cutaneous mechanoreceptors in the fingertips is important in effective object manipulation, allowing appropriate scaling of grip and load forces during precision grip. However, the role of mechanoreceptor subtypes in these tasks remains incompletely understood. To address this issue, psychophysical tasks that may specifically assess function of type I fast-adapting (FAI) and slowly adapting (SAI) mechanoreceptors were used with object manipulation experiments to examine the regulation of grip force control in an experimental model of graded reduction in tactile sensitivity (healthy volunteers wearing 2 layers of latex gloves). With gloves, tactile sensitivity decreased significantly from 1.9 ± 0.4 to 12.3 ± 2.2 μm in the Bumps task assessing function of FAI afferents but not in a grating orientation task assessing SAI afferents (1.6 ± 0.1 to 1.8 ± 0.2 mm). Six axis force/torque sensors measured peak grip (PGF) and load (PLF) forces generated by the fingertips during a grip-lift task. With gloves there was a significant increase of PGF (14 ± 6%), PLF (17 ± 5%), and grip and load force rates (26 ± 8%, 20 ± 8%). A variable-weight series task was used to examine sensorimotor memory. There was a 20% increase in PGF when the lift of a light object was preceded by a heavy relative to a light object. This relationship was not significantly altered when lifting with gloves, suggesting that the addition of gloves did not change sensorimotor memory effects. We conclude that FAI fibers may be important for the online force scaling but not for the buildup of a sensorimotor memory.
Comparison of the Utilization of Endoscopy Units in Selected Teaching Hospitals Across Canada
Authors: Lalor E , Thomson ABR
Published: April 2016

There is no information on the number of endoscopic procedures performed at major teaching hospitals across Canada. The directors of endoscopy units at eight teaching hospitals from Halifax to Vancouver volunteered demographic information on the unit at their location. There was a very wide range of endoscopic utilization, with approximately comparable rates of out‐patient versus in‐patient procedures and of gastroscopies versus colonoscopies, but there was no obvious linking of the ratios of in‐patients:out‐patients versus total number of designated gastrointestinal beds or total number of hospital beds. Thus, the appropriateness of endoscopic procedures needs to be based on standards of practice and accepted indications. The number of endoscopies performed per endoscopy unit support staff varied widely (from 323.7 to 1065.3 per year), and it would be interesting to learn whether this represents an opportunity for cost‐saving in some units.
Elevated Aminotransferase Activity as an Indication of Muscular Dystrophy: Case Reports and Review of the Literature
Authors: Zamora S , Adams C , Butzner JD , Machida H , Scott Rb
Published: April 2016

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identify the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome‐linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower’s sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease ‐ most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.
Immunocytochemical and Morphometric Studies of Gastrin‐, Somatostatin‐ and Serotonin‐Producing Cells in the Stomach and Duodenum of Patients with Acid Peptic Disorders
Authors: Yacoub WR , Thomson ABR , Hooper P , Jewell LD
Published: April 2016

Gastric and duodenal biopsies from 90 patients with various acid peptic disorders ‐ reflux esophagitis (n=24), gastric ulcer (n=13), duodenal ulcer (n=47) and nonulcer dyspepsia (n=6) ‐ were examined. Seven patients with minimal dyspeptic symptoms and an endoscopically and histologically normal stomach and duodenum served as controls. Immunoperoxidase staining for gastrin‐producing G cells, somatostatin‐producing D cells and serotonin‐producing EC cells was carried out on fundic, antral and duodenal biopsies, and was quantified using a Zeiss MOP Videoplan using the peroxidase‐antiperoxidase technique of Sternberger. In the gastric antrum, a G:D:EC cell ratio of approximately 1.6:1:1 was observed. In the duodenum the corresponding ratio was 1:1:2.4. No significant differences were observed within any of the major diagnostic categories. Patient age, sex, duration of symptoms, smoking habits, alcohol consumption and nonsteroidal anti‐inflammatory drug use had no effect on endocrine cell densities. Reduced G cell density in the descending duodenum was observed in the presence of mild duodenitis in four patients. In four patients with evidence of antral intestinal metaplastic changes, a significant increase in duodenal G cell densities was found. These results suggest that a change in the number of G, D or EC cells does not play a primary role in the pathophysiology of acid peptic disorders in the majority of patients.
A Hypothesis for Explaining the Geographical Distribution of Crohn’s Disease
Authors: Tamboli Cyrus P
Published: April 2016

The etiology of Crohn’s disease (CD) remains unknown, although there is epidemiological evidence supporting an environmental influence. Recent molecular techniques, including polymerase chain reaction, have renewed interest in a possible etiological role ofMycobacterium paratuberculosis, which has been isolated from a number of CD patients. The organism causes a chronic enteritis in animals called paratuberculosis, a condition with many clinical and pathological similarities to CD. This review compares the epidemiology of paratuberculosis in animals with the epidemiology of CD in humans. There is considerable overlap of regions with high prevalences of paratuberculosis and CD. This finding adds support to the implication ofM paratuberculosisin the etiology of CD.
Impact of Disease Activity on the Quality of Life of Crohn’s Disease Patients
Authors: Vallis T Michael , Turnbull Geoffrey K
Published: April 2016

Crohn’s disease (CD) patients often suffer severe symptoms that impair their quality of life. A sample of 39 CD patients who were assessed using well validated measures of disease activity and disease‐specific quality of life is reported. Twenty‐six of these patients were reassessed an average of four months after the initial assessment to determine the impact of changes in disease activity on quality of life. For the total sample (n=39) disease activity did not predict quality of life for any of the scales of the Inflammatory Bowel Disease Questionnaire (IBDQ) (r<0.13 for each). Thus, examining fluctuations in disease activity between patients did not demonstrate a disease activity‐quality of life relationship. In contrast, changes in disease activity within the same individuals over time (the repeat assessment sample, n=26) were correlated with changes in quality of life; increases in disease activity predicted decreases in quality of life on the IBDQ bowel symptoms subscale (r=‐0.463, P<0.01) and the IBDQ systemic symptoms subscale (r=0.44, P<0.05). The 10 patients with the largest decrease in disease activity over time (mean decrease of 43.54 points using the Dutch Activity Index) had significant improvement in quality of life on the bowel and systemic subscales. In contrast, the nine patients with the largest increase in disease activity over time (mean increase of 20.57 points using the Dutch Activity Index) had significant reduction in quality of life on the bowel and systemic symptoms subscales. These differences between extreme groups were significant for both the bowel symptoms (P<0.05) and systemic symptoms (P<0.05) subscales. The authors conclude that changes in disease activity affect some important aspects of quality of life: aspects related to disease‐specific (bowel symptoms) and nondisease‐specific (systemic symptoms) physical symptoms. Importantly, disease activity was not able to predict the emotional and social aspects of IBD‐related quality of life. This suggests that nondisease factors need to be considered when working with CD patients. Future research should evaluate the role of psychological intervention in improving quality of life for patients with reduced well‐being, particularly in areas of emotional and social functioning.
Regulation of Mucosal Immune Responses – The Missing Link in IBD?
Authors: Elson Charles O , Mccabe Robert P , Beagley Kenneth W , Sharmanov Almaz , Brandwein Steven L , Ridwan Ben U , Weaver Casey , Bucy R Patrick , Mcghee Jerry R , Sundberg John , Birkenmeier Edward
Published: April 2016

Although the etiology of inflammatory bowel disease (IBD) remains unknown, a major working hypothesis is that it represents a dysregulated immune response to common enteric bacterial antigens. Until recently there has been a relative dearth of experimental models to study this hypothesis. However, exciting developments in experimental models of colitis, including spontaneous, transgenic and knockout mice, now allow this and other hypotheses to be tested. The regulation of mucosal immune responses is not well understood in the normal animal, much less in those with chronic intestinal inflammation. Clearly the CD4 Th1 and Th2 pathways are important in the host response to microbial pathogens, and recent data indicate that the intestinal mucosa seems to be a site of preferential Th2 responses toward exogenous antigens. Deletion of certain cytokine genes involved in maintaining this Th1/Th2 balance (interleukin [IL]‐2, IL‐10) resulted in colitis, although deletion of others (IL‐4, interferon‐gamma) that are also involved did not. Whether these cytokine gene deletions cause a dysregulation of the mucosal immune response has yet to be shown. However, the importance of regulation can be demonstrated in a model in which a normal CD4+ T cell subset (CD45Rbhigh) is transferred into syngeneic severe combined immunodeficiency syndrome recipients. This results in a striking colitis over the ensuing weeks with chronic diarrhea and wasting of the animals. If the reciprocal CD4+ subset (CD45Rblow) is co‐transferred or if whole CD4+ T cells are transferred no colitis ensues. Therefore, T cells capable of causing colitis are present in normal animals but are prevented from doing so by immunoregulatory mechanisms. The antigens that drive the colitis in several of these models (IL‐2 knockout mouse, human leukocyte antigen B27/β2M transgenic rat) appear to be those of the normal enteric bacterial flora because germ‐free animals do not get the disease. Spontaneously colitic C3H/HeJBir mice also show prominent reactivity to enteric bacterial antigens. There are major differences among inbred mouse strains in susceptibility to colitis. The genes involved are not yet identified, but newly available technologies should allow that. In summary, these new models provide an experimental foundation to one of the major hypotheses on the cause of IBD, and will allow dissection of the genetic, environmental and immune components contributing to chronic colitis.
Late Acute Rejection Occuring in Liver Allograft Recipients
Authors: Yoshida Eric M , Shackleton Christopher R , Erb Siegfried R , Scudamore Charles H , Mori Rn Lynn M , Ford Jo-Ann E , Eggen Heather , Wynn Victoria , Partovi Nilufar , Keown Paul A
Published: April 2016

To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR) in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were retrospectively reviewed for the nearest 12‐week period preceding six episodes of LAR in five liver allograft recipients (group 1). Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2). LAR was defined as acute rejection occurring more than 365 days post‐transplantation. Median follow‐up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant). Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL) but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007) and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03) were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83%) of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8%) receiving prednisone 5 mg/day or more (P=0.004). In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post‐transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.
Helicobacter pylori: From Infection to Cure
Authors: Thomson ABR
Published: April 2016

Over 380 abstracts, presentations and posters of recent advances were highlighted at the European and InternationalHelicobacter pylorimeeting held July 7 to 9, 1995 in Edinburgh, Scotland. New advances abound, with major interest focusing on the simple, safe, inexpensive new `gold standard’ forH pylorieradication therapy: a single week of tid omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg, or omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. To avoid false negative results, two biopsies must be taken from the antrum and two from the gastric body at least four weeks after completion of eradication therapy, and ideally should be supplemented with at least one furtherH pyloritest such as a biopsy for urease activity or culture, or a urea breath test. While most patients with a gastric or duodenal ulcer (DU) who do not consume nonsteroidal anti-inflammatory drugs are infected withH pylori, the association is much less apparent in those with a DU who present with an upper gastrointestinal hemorrhage.H pylorieradication for nonulcer dyspepsia is not widely recommended, and the patient with a DU given effectiveH pylorieradication who presents with dyspepsia likely has erosive esophagitis rather than recurrent DU orH pylori. Gastroenterologists are at increased risk ofH pyloriinfection, particularly older gastroenterologists who are very busy endoscopists.
Pas de Deux: Active Ulcerative Colitis in an HIV‐Positive Patient
Authors: Pearson David C , Sutherland Lloyd R , Urbanski Stephan
Published: April 2016

A 40‐year‐old male who was found to be human immunodeficiency virus‐positive when he presented with bloody diarrhea in 1986 is described. Clinical, laboratory, endoscopic and histological findings were all compatible with ulcerative colitis, and stool cultures were repeatedly negative for pathogens. Colitis was initially mild and controlled with intermittent oral aminosalicylic acid products. Since 1993 he has had more significant symptoms requiring prednisone up to 40 mg/day. Repeat colonoscopy disclosed pancolitis and biopsies did not show evidence of cytomegalovirus infection. He has not had an acquired immune deficiency syndrome‐defining illness. CD4 cells fell below normal as his colitis worsened. This case raises questions about immune regulation in ulcerative colitis because the patient has active disease in addition to a reduced number of T helper cells. It also presents a difficult management problem because the patient has a limited life expectancy and is reluctant to accept colectomy, and further immunosuppressive therapy may be dangerous.
Osteoporosis of Crohn’s Disease: A Critical Review
Authors: Abraham Neena S , Fedorak Richard N
Published: April 2016

Osteoporosis has long been a recognized complication of Crohn’s disease (CD), with a documented incidence ranging from 31% to 65%. The cause of osteoporosis in Crohn’s patients is likely multifactorial; corticosteroids, inflammatory cytokines, small bowel resection and the resultant calcium and vitamin D deficiencies, hypogonadism, malnutrition and the cachexia of inflammation all play a role. However, the mechanism responsible for osteoporosis associated with CD remains unclear. Treatment of decreased bone density in CD patients has been limited to calcium and vitamin D replacement. The present understanding of the pathophysiology, mechanism and treatment of osteoporosis in CD is reviewed, with the focus on the role of steroid‐induced osteoporosis and the use of bisphosphonates.
Mucin in Primary Liver Carcinomas: Combined Hepatocellular‐Cholangiocarcinoma or Variant Hepatocellular Carcinoma
Authors: Hirota Shigeru , Nomoto Minoru , Hosobe Sadahiro , Aoyagi Yutaka , Asakura Hitoshi
Published: April 2016

OBJECTIVE: To investigate whether the presence of mucin defines a combined hepatocellular‐cholangiocarcinoma or merely a variant of usual hepatocellular carcinoma (HCC).

METHODS: From 1979‐92, 124 cases of usual HCC were studied at Niigata University Hospital, Niigata City, Japan, and several affiliated hospitals. Histological diagnoses were determined according to World Health Organization (WHO) criteria. Hematoxylin and eosin stain, periodic acid‐Schiff (PAS) stain, PAS stain after diastase digestion (D‐PAS) and silver stain tests were performed. Cases containing D‐PAS‐positive substances were also stained by Alcian blue (AB) stain, high iron diamine (HID) stain and concanavaline A paradox‐3 type (ConA3) stain. The classification of mucin was determined by AB, HID and ConA3 stains.

RESULTS: Mucin was recognized in the area of HCC by mucin stains in 25 of 124 cases. Two forms of mucin existence were classified: extracellular and intracellular. Mucins were classified by histochemical stains into three types: sulfomucin, sialomucin and neutral mucin.

CONCLUSIONS: According to the WHO histological classification of primary carcinoma of the liver, mucin existence is characteristic of intrahepatic cholangiocarcinoma. But if mucin exists in morphologically usual HCC, it is better to diagnose it as a variant of HCC (with mucin) rather than as a combined hepatocellular‐cholangiocarcinoma.
Validation of a New Saliva Test for Helicobacter pylori Infection
Authors: Bathe OF , Rae AJ , Zetler P , Cleator IGM
Published: April 2016

The purpose of this study was to evaluate a recently introduced saliva test measuring immunoglobulin (Ig) G antibodies to Helicobacter pylori by enzyme‐linked immunosorbent assay (ELISA). ELISA has previously been validated against IgG serological tests; however, it is not considered the definitive test for H pylori infection. Using endoscopic antral biopsies as the ’gold standard’ for comparison, the saliva test was validated on 70 patients with upper gastrointestinal symptoms admitted to St Paul’s Hospital Gastroenterology Clinic for gastroduodenoscopy. Thirty‐five patients (50%) had histological evidence of gastritis and, by using acridine orange stain, the bacterium was visualized in 25 patients (71%). A biopsy was considered positive when the bacterium was visualized. The saliva test was determined to be 80% sensitive and 80% specific for H pylori infection when the cut‐off for a positive test was 0.3 ELISA U/mL. Positive and negative predictive values were 69% and 88%, respectively. More study is required to assess the clinical utility of the test.
Lack of Effect of H2-Receptor Antagonists and Antacids on the Gastric and Duodenal Gastrin-, Somatostatin- and Serotonin-Producing Cells in Patients with Acid Peptic Disorders
Authors: Yacoub WR , Thomson ABR , Hooper P , Jewell LD
Published: April 2016

Standard therapeutic approaches to acid peptic disorders have dealt with neutralizing or inhibiting aggressive factors and/or bolstering defensive factors. Gastric and duodenal mucosal biopsies were examined from 90 patients with various acid peptic disorders, as follows: reflux esophagitis (n=24), gastric ulcer (n=13), duodenal ulcer (n=47) and nonulcer dyspepsia (n=6). Seven patients with minimal dyspeptic symptoms and an endoscopically and histologically normal stomach and duodenum served as controls. Immunoperoxidase staining for gastrin-producing G cells, somatostatin-producing D cells and serotonin-producing EC cells was carried out on fundic, antral and duodenal biopsies, and quantitated using a Zeiss MOP videoplan. No significant effects secondary to treatment with antacid, ranitidine or cimetidine were observed on endocrine cell densities and ratios. Biopsies obtained on different occasions over time indicated that in patients on enprostil (a synthetic E2prostaglandin), there was a trend towards increasing cell counts, suggesting that the serum gastrin-lowering effect of this drug may result from inhibition of gastrin release. Thus, H2-receptor antagonists and antacids do not alter gastric or duodenal mucosal G, D or EC cells in patients with acid peptic disorders.
Immunomodulation of Epithelium
Authors: Perdue Mary H
Published: April 2016

Many studies have provided evidence that the immune system is a key regulatory system of intestinal function. The interaction of immune cells with the gut epithelium plays an important role in host defence, acting to eliminate pathogens, antigens and other noxious material from the lumen of the gastrointestinal tract. During inflammatory conditions of the gut, the mucosa becomes packed with immune cells in close proximity to the enterocytes. Mediators released from these cells have profound effects on epithelial functions. The two main functions of the intestinal epithelium are to transport nutrients, ions and water, and to act as a barrier to prevent unimpeded uptake of antigenic material and microbes from the lumen. Both these functions are altered by immune reactions in response to various stimuli. Topics discussed include mast cells and epithelial function; mast cell-nerve interaction; mast cell activation; neutrophils, eosinophils and macrophages; T cells; and prostaglandins and immune cell activation.
Fatal Hepatic Decompensation in a Patient with Hepatitis B Cirrhosis Following Famciclovir Withdrawal
Authors: Myers Robert P , Chaudhary Rabindra , Fonseca Kevin , Lee Samuel S
Published: April 2016

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. Famciclovir is a nucleoside analogue with potent antiviral activity that appears promising in the management of patients with HBV infection. No data exist regarding the safety of nucleoside analogue withdrawal in patients treated for HBV cirrhosis. The authors describe a 41-year-old man with compensated HBV cirrhosis who developed fatal hepatic decompensation due to a rebound in viral replication within six weeks of discontinuing famciclovir therapy. Although several mutations in the HBV DNA polymerase gene have been documented, none has been associated with famciclovir resistance or adverse clinical outcomes. Clinicians should consider the risk of inducing serious flares in hepatic inflammation as a result of abrupt nucleoside analogue withdrawal. Until further data are available regarding the safety of withdrawal of these agents, indefinite treatment may be required in patients with established cirrhosis.
Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer
Authors: Nakagoe Tohru , Fukushima Kiyoyasu , Nanashima Atsushi , Sawai Terumitsu , Tsuji Takashi , Jibiki Masaaki , Yamaguchi Hiroyuki , Yasutake Toru , Ayabe Hiroyoshi , Matuo Tatsuki , Tagawa Yutaka , Arisawa Kokichi
Published: April 2016

BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)xantigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.

PURPOSE: To clarify the prognostic value of Lea, sialyl Lea, Lexand sialyl Lexexpression in colorectal carcinomas as prognostic factors after surgery.

PATIENTS AND METHODS: Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemical analyses for Lea, sialyl Lea, Lexand sialyl Lexexpression with the respective monoclonal antibodies.

RESULTS: Lea, sialyl Lea, Lexand sialyl Lexwere expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Lex-expressing tumours had more advanced cancer than those with nonsialyl Lex-expressing tumours (P=0.0029). The survival time after surgery of patients with Lex- or sialyl Lex-expressing tumours was significantly shorter than the survival time of those with non-Lex- or nonsialyl Lex-expressing tumours, respectively (P=0.023 and P=0.0001, respectively). Cox’s regression analysis revealed that Lexand sialyl Lexexpression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Lex-positive expression to sialyl Lex-negative expression 2.90; HR for Lex-positive expression to Lex-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III).

CONCLUSIONS: Lexexpression and sialyl Lexexpression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.