bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep sequencing the circadian and diurnal transcriptome of Drosophila brain
Authors: Hughes Michael E. , Grant Gregory R. , Paquin Christina , Qian Jack , Nitabach Michael N.
Published: April 2012

Eukaryotic circadian clocks include transcriptional/translational feedback loops that drive 24-h rhythms of transcription. These transcriptional rhythms underlie oscillations of protein abundance, thereby mediating circadian rhythms of behavior, physiology, and metabolism. Numerous studies over the last decade have used microarrays to profile circadian transcriptional rhythms in various organisms and tissues. Here we use RNA sequencing (RNA-seq) to profile the circadian transcriptome of Drosophila melanogaster brain from wild-type and period-null clock-defective animals. We identify several hundred transcripts whose abundance oscillates with 24-h periods in either constant darkness or 12 h light/dark diurnal cycles, including several noncoding RNAs (ncRNAs) that were not identified in previous microarray studies. Of particular interest are U snoRNA host genes (Uhgs), a family of diurnal cycling noncoding RNAs that encode the precursors of more than 50 box-C/D small nucleolar RNAs, key regulators of ribosomal biogenesis. Transcriptional profiling at the level of individual exons reveals alternative splice isoforms for many genes whose relative abundances are regulated by either period or circadian time, although the effect of circadian time is muted in comparison to that of period. Interestingly, period loss of function significantly alters the frequency of RNA editing at several editing sites, suggesting an unexpected link between a key circadian gene and RNA editing. We also identify tens of thousands of novel splicing events beyond those previously annotated by the modENCODE Consortium, including several that affect key circadian genes. These studies demonstrate extensive circadian control of ncRNA expression, reveal the extent of clock control of alternative splicing and RNA editing, and provide a novel, genome-wide map of splicing in Drosophila brain.
Peroxiredoxin‐1, a possible target in modulating inflammatory cytokine production in macrophage like cell line RAW264.7
Authors: Tae Lim Young , Sup Song Dong , Joon Won Tae , Lee Yun‐Jung , Yoo Jong‐Sun , Eun Hyung Kyeong , Won Yoon Joo , Park So‐Young , Woo Hwang Kwang
Published: April 2012

Peroxiredoxin (PRX), a scavenger of H2O2 and alkyl hydroperoxides in living organisms, protects cells from oxidative stress. Contrary to its known anti‐oxidant roles, the involvement of PRX‐1 in the regulation of lipopolysaccharide (LPS) signaling is poorly understood, possible immunological functions of PRX‐1 having been uncovered only recently. In the present study, it was discovered that the PRX‐1 deficient macrophage like cell line (RAW264.7) has anti‐inflammatory activity when stimulated by LPS. Treatment with LPS for 3 hrs resulted in increased gene expression of an anti‐inflammatory cytokine, interleukin‐10 (IL‐10), in PRX‐1 knock down RAW264.7 cells. Gene expression of pro‐inflammatory cytokines IL‐1β and tumor necrosis factor‐ α (TNF‐α) did not show notable changes under the same conditions. However, production of these cytokines significantly decreased in PRX‐1 knock down RAW264.7 cells with 12 hrs of stimulation. Production of IL‐10 was also increased in PRX‐1 knock down RAW264.7 cells with 12 hrs of stimulation. We predicted that higher concentrations of IL‐10 would result in decreased expression of IL‐1β and TNF‐α in PRX‐1 knock‐down cells. This was confirmed by blocking IL‐10, which reestablished IL‐1β and TNF‐α secretion. We also observed that increased concentrations of IL‐10 do not affect the NF‐κB pathway. Interestingly, STAT3 phosphorylation by LPS stimulation was significantly increased in PRX‐1 knockdown RAW264.7 cells. Up‐regulation of IL‐10 in PRX‐1 knockdown cells and the resulting downregulation of proinflammatory cytokine production seem to involve the STAT3 pathway in macrophages. Thus, down‐regulation of PRX‐1 may contribute to the suppression of adverse effects caused by excessive activation of macrophages through affecting the STAT3 signaling pathway.
Herpes simplex virus US3 protein kinase regulates host responses and determines neurovirulence
Authors: Mori Isamu
Published: April 2012

The US3 of HSV encodes a serine/threonine protein kinase that is highly conserved among members of the alphaherpesviruses. It is an accessory gene that is not required for viral replication in cultured cells but appears essential for viral survival in humans. Although accumulating in vitro evidence suggested that the viral protein kinase is multifunctional, little information is available about its functions in vivo. Several reports point out that, upon invasion into the peripheral nervous system, HSV blocks virus‐induced neuronal apoptosis, while presumably subverting host immune responses, largely through actions of the US3 protein kinase. In addition, the US3 protein kinase confers the viral neurovirulence. In the present article, functions of the HSV US3 protein kinase are briefly reviewed, with special attention given to its role in regulating host responses and neurovirulence.
The Top 10 fungal pathogens in molecular plant pathology
Authors: DEAN RALPH , VAN KAN JAN A. L. , PRETORIUS ZACHARIAS A. , HAMMOND‐KOSACK KIM E. , DI PIETRO ANTONIO , SPANU PIETRO D. , RUDD JASON J. , DICKMAN MARTY , KAHMANN REGINE , ELLIS JEFF , FOSTER GARY D.
Published: April 2012

The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a ‘Top 10’ based on scientific/economic importance. The survey generated 495 votes from the international community, and resulted in the generation of a Top 10 fungal plant pathogen list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Magnaporthe oryzae; (2) Botrytis cinerea; (3) Puccinia spp.; (4) Fusarium graminearum; (5) Fusarium oxysporum; (6) Blumeria graminis; (7) Mycosphaerella graminicola; (8) Colletotrichum spp.; (9) Ustilago maydis; (10) Melampsora lini, with honourable mentions for fungi just missing out on the Top 10, including Phakopsora pachyrhizi and Rhizoctonia solani. This article presents a short resumé of each fungus in the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant mycology community, as well as laying down a bench‐mark. It will be interesting to see in future years how perceptions change and what fungi will comprise any future Top 10.
Family‐centred residential care: the new reality?
Authors: Geurts Esther M. W. , Boddy Janet , Noom Marc J. , Knorth Erik J.
Published: April 2012

This paper considers therapeutic approaches to residential care with specific attention to the question of family involvement. It builds on a body of literature indicating the potential of residential care as a positive intervention for young people, and examines the contention that – even when family problems contribute to a young person's accommodation in residential care – family involvement could improve long‐term outcomes. The literature reviewed indicates that family involvement is indeed important. Mixed research findings reflect the diversity of approaches to family‐centred practice, but there is evidence of benefits in relation to a range of child outcomes. However, the literature also shows that family‐centred residential care is not easy to achieve. More than parent–child contact, it entails genuine involvement of parents, in decision‐making and in children's daily lives. Professionals – including social workers and residential care workers – must not only be concerned with the care and development of the child, but also with the role of the parent in their child's development, understood within an ecological perspective.
Gorse (Ulexspp.) use by ponies in winter: Is the spatial pattern of browsing independent of the neighbouring vegetation?
Authors: Aldezabal A. , Mandaluniz N. , Laskurain N. A.
Published: April 2012

Because of the progressive abandonment of agricultural practices, the extension of Atlantic dry gorse/heathlands has increased in the Cantabrian Mountains. However, there is a remarkable lack of knowledge on the spatial use of gorse by grazing animals. This study was designed to examine whether the spatial pattern of gorse browsing was independent of the neighbouring vegetation. In addition, factors that could determine the grazing/browsing pattern were investigated. For this purpose, we conducted a spatially controlled experiment using Basque Ponies (an endangered and rustic horse breed) in winter by simulating short‐term grazing at a moderate stocking rate. Measurements of size and nutritive value of grass and gorse patches were made before and after grazing to analyse grazing pressure and browsing impact. Browsing damage did not occur randomly. Sward height of grass patches was the best predictor of feeding site selection, and gorse patch edges surrounding the most‐used grass patches were browsed with a greater intensity. This foraging strategy appears to be the result of a trade‐off between maximization of intake rate and nutritive benefits. Our results highlight the importance of spatial information for predicting gorse utilization by grazing equids, in particular the effect of utilization of gorse/grass edge. We conclude that these ponies could be a suitable tool for restoring abandoned gorse shrublands.
Timing of breeding carries over to influence migratory departure in a songbird: an automated radiotracking study
Authors: Mitchell Greg W. , Newman Amy E. M. , Wikelski Martin , Ryan Norris D.
Published: April 2012

1. Determining how events interact across stages of the annual cycle is critical for understanding the factors that affect individual fitness. However, there is currently little information detailing how breeding events influence migratory behaviour.

2. Using an automated digital telemetry array and an isolated island‐breeding population of Savannah sparrows Passerculus sandwichensis, we provide the first direct evidence that the timing of breeding events carries over to influence the timing of migration in a songbird and assess for the first time how weather conditions on the breeding grounds also affect departure dates.

3. Date of migratory departure between September and October was strongly influenced by date of breeding completion in adults and fledging date in juveniles from June to July.

4. With respect to weather, adults departed during the first half of high‐pressure systems, while juveniles departed throughout the entirety of high‐pressure systems (including rainy evenings on the western edge of systems).

5. By combining both ecological and weather data, we could explain almost all variation in departure date for adults (95%), but weather conditions were not a good predictor of departure date for juveniles.

6. Our results provide strong evidence that the timing of breeding events is an important driver of migration timing and that exact departure dates are fine‐tuned according to local weather conditions in adults, but not in juveniles.
What makes a healthier nurse, workplace or leisure physical activity? Informed by the Australian and New Zealand e‐Cohort Study
Authors: Henwood Tim , Tuckett Anthony , Turner Catherine
Published: April 2012

Aim and objective.  To investigate health differences between nurses who report meeting the daily physical activity recommendations in or away from the workplace.

Background.  Adhering to the national physical activity recommendations has known health benefits. Whilst often considered a workplace active profession, data are emerging of poor health amongst nurses. However, health differences between workplace or leisure‐time physically active nurses are understudied.

Design.  The investigation is an observation study of Australian and New Zealand nurses. Data were generated from the longitudinal, population‐based, observational e‐Cohort nursing survey.

Methods.  Data were informed and groups defined by the self‐reported minutes per day of moderate physical activity collected from a large international survey of practicing nurses (n = 2264). Groups were: Group (G) 1 – high workplace (≥30 minutes/day)/high leisure (≥30 minutes/day), G2 – high workplace/low leisure (<30 minutes/day), G3 – low workplace/low leisure (<30 minutes/day) and G4 – low workplace/high leisure.

Results.  G2 had a high BMI and were younger than G4. G4 were significantly more active away from work and more likely to report cycling to work than G2. In contrast, G2 were most likely to have taken sick days because of their health (χ2 = 19·101), have difficulty sleeping most of the time and have a medical history of diagnosed anxiety and depression.

Conclusions.  This study shows that improved well‐being can be achieved in nursing cohort through leisure‐time physical activity.

Relevance to clinical practice.  This research shows that nurse should consider leisure‐time physical activity necessary to maintain and prolong health and that workplace activity is not a sufficient stimulus. This has important implications for workforce planners and administrators.
Behavioural phenotypes and special educational needs: is aetiology important in the classroom?
Authors: Reilly C.
Published: April 2012

Background A number of genetic conditions with associated intellectual disability and/or special educational needs have increasingly well‐defined behavioural phenotypes. Thus, the concept of ‘behavioural phenotype’ and aetiology of intellectual disability may be important with regard to school‐based interventions.

Method The evidence for distinctive cognitive and behavioural aspects of five of the most common genetic syndromes (Down syndrome, fragile X syndrome, Williams syndrome, Prader–Willi syndrome and velo‐cardio‐facial syndrome) associated with special educational needs is reviewed with respect to key studies and findings. The possible utility of aetiology‐related interventions in education is discussed with reference to arguments for and against such approaches with respect to published guidelines and published research.

Results Behavioural phenotypes are probabilistic and many children with a specific genetic syndrome will share commonalities with other children with other genetic syndromes and within syndrome variability is not uncommon. There is evidence that teachers and parents have limited knowledge of aspects of the proposed cognitive and behaviour profiles associated with the reviewed syndromes. While there are published guidelines in the area of learning and behaviour for each of the five reviewed syndromes there is a limited amount of evidence of the efficacy of such approaches in school settings.

Conclusion It is likely that knowing the aetiology of a child's special educational needs will be helpful for staff who work in school settings in relation to cognitive and behavioural implications. However, how such knowledge might inform teaching practice or behavioural interventions has not been studied. A model is proposed that might help inform educators about the possible role of aetiology in the classroom.
Interferometer‐based structured‐illumination microscopy utilizing complementary phase relationship through constructive and destructive image detection by two cameras
Authors: SHAO L. , WINOTO L. , AGARD D.A. , GUSTAFSSON M.G.L. , SEDAT J.W.
Published: April 2012

In an interferometer‐based fluorescence microscope, a beam splitter is often used to combine two emission wavefronts interferometrically. There are two perpendicular paths along which the interference fringes can propagate and normally only one is used for imaging. However, the other path also contains useful information. Here we introduced a second camera to our interferometer‐based three‐dimensional structured‐illumination microscope (I5S) to capture the fringes along the normally unused path, which are out of phase by π relative to the fringes along the other path. Based on this complementary phase relationship and the well‐defined phase interrelationships among the I5S data components, we can deduce and then computationally eliminate the path length errors within the interferometer loop using the simultaneously recorded fringes along the two imaging paths. This self‐correction capability can greatly relax the requirement for eliminating the path length differences before and maintaining that status during each imaging session, which are practically challenging tasks. Experimental data is shown to support the theory.
Brain Processing of Duodenal and Portal Glucose Sensing
Authors: Boubaker J. , Val‐Laillet D. , Guérin S. , Malbert C.‐H.
Published: April 2012

Peripheral and central glucose sensing play a major role in the regulation of food intake. Peripheral sensing occurs at duodenal and portal levels, although the importance of these sensing sites is still controversial. The present study aimed to compare the respective influence of these sensing pathways on the eating patterns; plasma concentrations of glucose, insulin and glucagon‐like peptide‐1 (GLP‐1); and brain activity in juvenile pigs. In Experiment 1, we characterised the changes in the microstructure as a result of a 30‐min meal in eight conscious animals after duodenal or portal glucose infusion in comparison with saline infusion. In Experiment 2, glucose, insulin and GLP‐1 plasma concentrations were measured during 2 h after duodenal or portal glucose infusions in four anaesthetised animals. In Experiment 3, single photon emission computed tomography brain imaging was performed in five anaesthetised animals receiving duodenal or portal glucose or saline infusions. Both duodenal and portal glucose decreased the amount of food consumed, as well as the ingestion speed, although this effect appeared earlier with the portal infusion. Significant differences of glucose and GLP‐1 plasma concentrations between treatments were found at the moment of brain imaging. Both duodenal and portal glucose infusions activated the dorsolateral prefrontal cortex and primary somatosensory cortex. Only duodenal glucose infusion was able to induce activation of the prepyriform area, orbitofrontal cortex, caudate and putamen, as well as deactivation of the anterior prefrontal cortex and anterior entorhinal cortex, whereas only portal glucose infusion induced a significant activation of the insular cortex. We demonstrated that duodenal and portal glucose infusions led to the modulation of brain areas that are known to regulate eating behaviour, which probably explains the decrease of food intake after both stimulations. These stimulation pathways induced specific systemic and central responses, suggesting that different brain processing matrices are involved.
Agrobacterium tumefaciens can obtain sulphur from an opine that is synthesized by octopine synthase using S‐methylmethionine as a substrate
Authors: Flores‐Mireles Ana Lidia , Eberhard Anatol , Winans Stephen C.
Published: April 2012

Agrobacterium tumefaciens incites plant tumours that produce nutrients called opines, which are utilized by the bacteria during host colonization. Various opines provide sources of carbon, nitrogen and phosphorous, but virtually nothing was previously known about how A. tumefaciens acquires sulphur during colonization. Some strains encode an operon required for the catabolism of the opine octopine. This operon contains a gene, msh, that is predicted to direct the conversion of S‐methylmethionine (SMM) and homocysteine (HCys) to two equivalents of methionine. Purified Msh carried out this reaction, suggesting that SMM could be an intermediate in opine catabolism. Purified octopine synthase (Ocs, normally expressed in plant tumours) utilized SMM and pyruvate to produce a novel opine, designated sulfonopine, whose catabolism by the bacteria would regenerate SMM. Sulfonopine was produced by tobacco and Arabidopsis when colonized by A. tumefaciens and was utilized as sole source of sulphur by A. tumefaciens. Purified Ocs also used 13 other proteogenic and non‐proteogenic amino acids as substrates, including three that contain sulphur. Sulfonopine and 11 other opines were tested for induction of octopine catabolic operon and all were able to do so. This is the first study of the acquisition of sulphur, an essential element, by this pathogen.
Meticillin‐resistantStaphylococcus pseudintermedius: clinical challenge and treatment options
Authors: Frank Linda A. , Loeffler Anette
Published: April 2012

Meticillin‐resistantStaphylococcus pseudintermedius(MRSP) has emerged as a major therapeutic challenge for small animal veterinarians over the past 10 years and continues to spread worryingly in many countries.

This review focuses on the clinical aspects of MRSP infections seen in patients with skin disease and on currently available treatment options. In addition, it discusses the implications for in‐contact people, other animals and the environment, because infection control strategies are likely to have a significant impact on treatment success and prevention of spread.

There is currently no indication that MRSP is more virulent than meticillin‐susceptibleS. pseudintermedius, and reported infections have mostly been treated successfully, although possibly with a longer time to resolution than infections with more susceptibleS. pseudintermedius. However,in vitrotesting of MRSP isolates indicates resistance to most or all antibacterial agents licensed for use in pets. Based on susceptibility results, the most useful systemic antimicrobials may include chloramphenicol, rifampicin, amikacin, clindamycin and/or minocycline. Adverse effects of some of these medications may limit their usefulness. Whilein vitrosusceptibility to vancomycin and linezolid is reported by some laboratories, use of these drugs in animals is strongly discouraged because of ethical considerations. Aggressive topical therapy has been effective as the only treatment in certain cases.

Awareness, continued research and comprehensive management of infections are required by veterinary practitioners not only to help treat infected animals but also to limit the spread and prevent the establishment of this highly drug‐resistant and zoonotic pathogen in veterinary facilities and in the community.
Spectrum of pediatric dermatological emergencies at a tertiary care hospital in India: a descriptive study
Authors: Mathias Rohini C. , Jayaseelan Elizabeth , Augustine Mary
Published: April 2012

Background  Dermatological emergencies in children are not uncommon. Worldwide, limited studies have been done to study the spectrum of such emergencies. The aim of our study was to analyze the spectrum of dermatological emergencies in the pediatric age group.

Materials and methods  Over a period of 18 months, ninety consecutive patients under 18 years of age presenting with cutaneous in addition to emergency disorders as assessed by the Nelson's severity scoring system were recruited.

Results  The most common emergency was primary cutaneous infections (40%), followed by adverse cutaneous drug reactions (13.33%). Staphylococcal scalded skin syndrome was the most frequent infection, and the most common adverse cutaneous drug reaction was Stevens–Johnson syndrome and toxic epidermal necrolysis. Other emergencies included purpura fulminans (12.22%), congenital dermatoses (11.11%), vasculitis (8.90%), angioedema (6.67%), collagen vascular diseases (2.22%), serum sickness (2.22%), post‐varicella cerebellitis (1.11%), post‐infected scabies glomerulonephritis (1.11%), and Langerhans cell histiocytosis (1.11%). These emergencies presented in equal numbers to the outpatient department of dermatology or pediatrics and to the emergency department.

Conclusion  Our study recommends the use of standard scoring systems such as the Nelson’s score to assess sick children. The appropriateness of this scale or other scales for the assessment of dermatological emergencies needs to be established. Over half of our cases were initially assessed by pediatricians and emergency personnel, highlighting the importance of spreading awareness about cutaneous emergencies and providing them with access to a dermatologist’s services.
Oxygen and anesthesia: what lung do we deliver to the post‐operative ward?
Authors: HEDENSTIERNA G.
Published: April 2012

Anesthesia is safe in most patients. However, anesthetics reduce functional residual capacity (FRC) and promote airway closure. Oxygen is breathed during the induction of anesthesia, and increased concentration of oxygen (O2) is given during the surgery to reduce the risk of hypoxemia. However, oxygen is rapidly adsorbed behind closed airways, causing lung collapse (atelectasis) and shunt. Atelectasis may be a locus for infection and may cause pneumonia. Measures to prevent atelectasis and possibly reduce post‐operative pulmonary complications are based on moderate use of oxygen and preservation or restoration of FRC. Pre‐oxygenation with 100% O2 causes atelectasis and should be followed by a recruitment maneuver (inflation to an airway pressure of 40 cm H2O for 10 s and to higher airway pressures in patients with reduced abdominal compliance (obese and patients with abdominal disorders). Pre‐oxygenation with 80% O2 may be sufficient in most patients with no anticipated difficulty in managing the airway, but time to hypoxemia during apnea decreases from mean 7 to 5 min. An alternative, possibly challenging, procedure is induction of anesthesia with continuous positive airway pressure/positive end‐expiratory pressure to prevent fall in FRC enabling use of 100% O2. A continuous PEEP of 7–10 cm H2O may not necessarily improve oxygenation but should keep the lung open until the end of anesthesia. Inspired oxygen concentration of 30–40%, or even less, should suffice if the lung is kept open. The goal of the anesthetic regime should be to deliver a patient with no atelectasis to the post‐operative ward and to keep the lung open.
Indocyanine green injection for detecting sentinel nodes using color fluorescence camera in the laparoscopy‐assisted gastrectomy
Authors: Yoshida Masashi , Kubota Keisuke , Kuroda Junko , Ohta Keiichiro , Nakamura Tetsuya , Saito Junichi , Kobayashi Michiya , Sato Takayuki , Beck Yoshifumi , Kitagawa Yuko , Kitajima Masaki
Published: April 2012

Background and Aim:  We seek for the accurate and simple method for detecting sentinel nodes of gastric cancer which can be popularized in community hospitals. The indocyanine green (ICG) fluorescence‐guided method is reported to be sensitive. However, the ordinal fluorescence cameras have gray scale imaging and require a dark room. We have developed a new device, Hyper Eye Medical System (HEMS) which can simultaneously detect color and near‐infrared rays and can be used under room light. This study was planned to examine whether submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery.

Methods:  The patients underwent gastrectomy for clinical T1a (mucosa)–T2 (muscularis propria) and clinical N0 were enrolled in the present study. As a preliminary trial, one case each of the ICG 25 and 100 µg/mL, injected on the day before operation and intraoperative injection, was examined. Then, 10 cases injected 50 µg/mL ICG on the day before operation were examined.

Results:  The ICG fluorescence of the patient injected 100 µg/mL was too intense and that of the patient injected 25 µg/mL was too faint. Sentinel lymph nodes were detected in all of 10 cases injected 50 µg/mL, the day before operation and number of sentinel lymph nodes per patient was 3.6 ± 2.1. Metastasis was observed in one case. All of ICG fluorescence‐positive sentinel nodes were positive for the metastasis. In the patient who underwent intraoperative injection, sentinel lymphatic basins could be identified.

Conclusion:  The present study shows that HEMS‐guided abdominal surgery is feasible under room light. Submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery.
Pathogenesis of proton‐pump inhibitor‐refractory non‐erosive reflux disease according to multichannel intraluminal impedance‐pH monitoring
Authors: Kohata Yukie , Fujiwara Yasuhiro , Machida Hirohisa , Okazaki Hirotoshi , Yamagami Hirokazu , Tanigawa Tetsuya , Watanabe Kenji , Watanabe Toshio , Tominaga Kazunari , Arakawa Tetsuo
Published: April 2012

Background and Aim:  Proton‐pump inhibitor (PPI) therapy is the first‐line treatment for gastroesophageal reflux disease; however, there are some reports of PPI failure in cases of non‐erosive reflux disease (NERD). Among the pathogenic factors associated with PPI‐refractory NERD, reflux other than acid reflux can not be detected by conventional pH monitoring. The purpose of this study was to clarify the usefulness of multichannel intraluminal impedance‐pH (MII‐pH) monitoring for PPI‐refractory NERD patients and examine the pathogenesis.

Methods:  We used MII‐pH monitoring to examine 29 PPI‐refractory NERD patients on PPI treatment. Reflux parameters, symptom index (SI: positive if ≥ 50%), and proximal migration were analyzed. The acidity of the reflux was divided into acid (nadir pH ≤ 4) and non‐acid (nadir pH > 4). Subjects were classified into reflux‐related disease (abnormal reflux parameters or positive SI) and non‐reflux‐related disease (normal reflux parameters and negative SI).

Results:  Of the 29 subjects, 21 were diagnosed with reflux‐related disease, including 6 with acid reflux type and 15 with non‐acid reflux type, and 8 were diagnosed with non‐reflux‐related disease. Of the total 1816 liquid reflux episodes, 834 showed proximal migration, which was more common in symptomatic reflux than in asymptomatic reflux.

Conclusions:  MII‐pH monitoring could distinguish reflux‐related disease (especially non‐acid type) from PPI‐refractory NERD. Proximal migration was associated with symptomatic reflux in PPI‐refractory NERD patients.
Correlation between Helicobacter pylori infection and low‐dose aspirin use on damage of the upper gastrointestinal tract
Authors: Fukuzawa Mari , Kawai Takashi , Watanabe Masataka , Tomiyama Hirofumi , Yamashina Akira , Moriyasu Fuminori
Published: April 2012

Background and Aim:  Low‐dose aspirin (LDA), and Helicobacter pylori (HP) infection are considered the two primary causes of peptic ulceration. The interaction between HP infection and non‐steroidal anti‐inflammatory drugs is, however, a matter of considerable discussion and controversy. In this study, we investigated possible synergistic or negative interactions between HP infection and LDA in gastric mucosal lesions, according to lesion site.

Methods:  The subjects were 120 patients attending the Cardiology Outpatients Department (average age, 67.1 ± 8.9 years; male : female ratio 2.9:1). Endoscopic findings were graded using the Modified Lanza score. Lesions were scored for the antral, body and fundal regions. Ulcers were defined as mucosal defects ≥ 5 mm in size.

Results:  There were 55 HP‐positive and 65 HP‐negative subjects, and 91 subjects on LDA therapy. The gastric antral Lanza scores were HP(−) LDA(−): 0.2 ± 1.6, HP(−) LDA(+): 1.8 ± 1.5, HP(+) LDA(−): 0.3 ± 0.7, and HP(+) LDA(+): 0.5 ± 1.0. The gastric body and fundal Lanza scores were 0.0 ± 0.0, 0.8 ± 0.9, 0.4 ± 1.1, and 1.0 ± 1.5, respectively, and 0.1 ± 0.3, 0.5 ± 0.9, 0.1 ± 0.3, and 0.1 ± 0.3, respectively. Variance analysis of the correlation between HP infection and LDA by regional Lanza scores identified both HP infection and LDA use as factors that significantly influence the antral Lanza score. However, LDA was an aggressive factor, and HP infection a protective factor. In the gastric body, LDA was a non‐significant, and HP infection a significant, aggressive factor. In the gastric fundus, neither HP infection nor LDA was a significant factor (LDA was an aggressive factor, and HP infection a protective factor).

Conclusions:  LDA had aggressive effects in all gastric lesions; on the other hand, HP infection had protective effects in the antrum and fundus in the stomach, and aggressive effects in the body in the stomach.
Laparoendoscopic single‐site cholecystectomy versus conventional laparoscopic cholecystectomy: a systematic review of randomized controlled trials
Authors: Wang Dong , Wang Yan , Ji Zhen‐Ling
Published: April 2012

Background:  Laparoendoscopic single‐site surgery is a revolution in minimally invasive surgery in recent years, and cholecystectomy is the most common intervention. However, laparoendoscopic single‐site cholecystectomy (LESSC) is a controversial procedure. Its safety, cosmetic results, complications, post‐operative pain and post‐operative stay are not confirmed by multi‐centre randomized controlled studies.

Objectives:  This review examined the impact of LESSC versus conventional laparoscopic cholecystectomy (CLC). The primary outcomes were conversional rate and intraoperative and post‐operative complications, and other outcomes were cosmetic results, operative time, post‐operative pain and post‐operative stay.

Data sources:  Pubmed, EMbase, Web of Science, Ovid, clinical trials of the US National Institutes of Health and Cochrane Database of Systematic Reviews and Controlled Trials Register were searched to identify all possible randomized controlled trials (RCTs).

Methods:  Two reviewers completed article search, and eligible data were entered into a computerized spreadsheet for analysis.

Results:  Nine studies were obtained using the search strategy. Patients accepting LESSC had a higher conversion rate than those having CLC (7.17 (3.00, 17.11) (P < 0.01)). There was no significant difference for total complications between the two groups (1.17 (0.76, 1.80) (P= 0.46)), but incidence of incisional hernia and haemorrhage (seroma) in the LESSC group was obviously higher than that in the CLC group. Operative time was much longer in the LESSC group (mean difference: 10.69 (3.14, 18.24) (P= 0.006)). Cosmetic results favoured LESSC; however, post‐operative abdominal pain and post‐operative stay were not significantly different between the two groups in most of the nine studies.

Conclusions:  LESSC can be safely performed with better cosmetic results; however, it carries a higher conversion rate and a longer operative time, and offers no benefit in terms of post‐operative abdominal pain and post‐operative stay. Further RCTs, according to the CONSORT statement, are advocated to validate its objective benefits.
Factors influencing career decisions in internal medicine
Authors: Macdonald C. , Cawood T.
Published: April 2012

Background:  Numerous factors influence career decisions for internal medicine trainees and Fellows. There is a perception that a greater emphasis is placed on work–family balance by younger physicians.

Aims:  To determine the characteristics of the modern internal medicine workforce and ascertain whether job flexibility is important to career decision‐making. We hypothesised that factors which reflect flexibility would be highly influential in decision‐making, especially for women and those with young children.

Methods:  A questionnaire was mailed to 250 New Zealand internal medicine trainees and Fellows. It focused on factors, including job flexibility, interest and collegial support, and included demographic details which were primarily aimed at ascertaining family responsibilities.

Results:  Response rate was 54%. The majority of female physicians are the main person responsible for their children (62%), and the majority of their partners work full‐time (80%). This contrasts with male physicians, of whom only 4% are the main person responsible for their children. Flexibility was found to be more influential in women, those with young children, trainees and those working in outpatient‐based subspecialties. However, contrary to our original hypothesis, flexibility was not reported to be highly influential in any group, with career choice being most influenced by interest and enjoyment, intellectual challenge and variety within the job.

Conclusion:  It is hoped that results will inform employers and those involved with training to enable them to better cater for the needs of the workforce and also encourage trainees to consider future family commitments when making career decisions.
Systematic review of the prevalence of gout and hyperuricaemia in Australia
Authors: Robinson P. C. , Taylor W. J. , Merriman T. R.
Published: April 2012

Aims:  Gout is a growing health problem worldwide especially in affluent countries, such as Australia. Gout and hyperuricaemia are associated with the metabolic syndrome, diabetes mellitus, obesity and hypertension. More importantly, Australia has a growing prevalence of these important health problems. The aim of this study was to systematically review published information regarding the prevalence of gout and hyperuricaemia in Australia.

Methods:  A systematic search was undertaken of the MEDLINE, EMBASE and Web of Science databases, as well as relevant websites for journal articles and reports relating to the prevalence of hyperuricaemia and gout in Australia.

Results:  Twenty‐five journal articles and five reports were included in the review. Data collected in a standardised way show gout increased in prevalence from 0.5% population prevalence to 1.7% population prevalence from 1968 to 1995/1996. There has been a significant rise in the prevalence of gout in the Australian Aboriginal population from 0% in 1965 to 9.7% in men and 2.9% in women in 2002. Consistent with the rise in gout prevalence, serum uric acid in blood donors has increased from 1959 to 1980 (17% in 30‐ to 40‐year‐old men).

Conclusions:  The rate of gout and hyperuricaemia in Australia is high in relation to comparable countries and is increasing. The prevalence of gout in elderly male Australians is second only to New Zealand, which has the highest reported rate in the world. Further research on Aboriginal and Torres Strait Islander gout and hyperuricaemia is required as a result of the lack of contemporary data.
Evaluation of an Australian chest pain assessment unit
Authors: Sonigra A. , Lawlor J. , Roberts L.
Published: April 2012

Background

In order to mitigate the risk of missing atypical or low probability presentations of acute coronary syndromes (ACS), many hospitals have designated resources specifically for the assessment of chest pain.

Aim

This study aims to evaluate the introduction of a chest pain assessment unit (CPAU) in a North Queensland hospital.

Methods

Information on admission status, diagnosis, procedures, length of stay and chest pain representation rates was obtained for patients presenting with chest pain to the emergency department (ED) at The Townsville Hospital in the 2.5 years prior to the introduction of a CPAU in March 2007 (n = 6665). This was compared with information on chest pain patients (n = 7885) presenting to the ED in the 2.5 years after it opened.

Results

The CPAU resulted in a reduction in the percentage of ‘missed’ cases of ACS. The rate of people who represented with chest pain at 3 months and who ultimately received an ACS diagnosis reduced from 1.9% to 1.4%. There was an increased rate of apparently appropriate angiograms from 6.7% to 9.4% of chest pain admissions. The admission rate of ED chest pain presentations was stable as was the median length of stay (1.14–1.16 days). A relative decrease in the proportion of admitted patients diagnosed with ACS compared with those with unspecified chest pain was observed.

Conclusion

The implementation of a CPAU at The Townsville Hospital resulted in improved care of those presenting to the ED with chest pain. Further Australian CPAU evaluations are recommended.
Dissociating hippocampal and striatal contributions to sequential prediction learning
Authors: Bornstein Aaron M. , Daw Nathaniel D.
Published: April 2012

Behavior may be generated on the basis of many different kinds of learned contingencies. For instance, responses could be guided by the direct association between a stimulus and response, or by sequential stimulus–stimulus relationships (as in model‐based reinforcement learning or goal‐directed actions). However, the neural architecture underlying sequential predictive learning is not well understood, in part because it is difficult to isolate its effect on choice behavior. To track such learning more directly, we examined reaction times (RTs) in a probabilistic sequential picture identification task in healthy individuals. We used computational learning models to isolate trial‐by‐trial effects of two distinct learning processes in behavior, and used these as signatures to analyse the separate neural substrates of each process. RTs were best explained via the combination of two delta rule learning processes with different learning rates. To examine neural manifestations of these learning processes, we used functional magnetic resonance imaging to seek correlates of time‐series related to expectancy or surprise. We observed such correlates in two regions, hippocampus and striatum. By estimating the learning rates best explaining each signal, we verified that they were uniquely associated with one of the two distinct processes identified behaviorally. These differential correlates suggest that complementary anticipatory functions drive each region’s effect on behavior. Our results provide novel insights as to the quantitative computational distinctions between medial temporal and basal ganglia learning networks and enable experiments that exploit trial‐by‐trial measurement of the unique contributions of both hippocampus and striatum to response behavior.
From prediction error to incentive salience: mesolimbic computation of reward motivation
Authors: Berridge Kent C.
Published: April 2012

Reward contains separable psychological components of learning, incentive motivation and pleasure. Most computational models have focused only on the learning component of reward, but the motivational component is equally important in reward circuitry, and even more directly controls behavior. Modeling the motivational component requires recognition of additional control factors besides learning. Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue‐triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. Thus, one consequence of the difference between incentive salience and learning can be to decouple cue‐triggered motivation of the moment from previously learned values of how good the associated reward has been in the past. Another consequence can be to produce irrationally strong motivation urges that are not justified by any memories of previous reward values (and without distorting associative predictions of future reward value). Such irrationally strong motivation may be especially problematic in addiction. To understand these phenomena, future models of mesocorticolimbic reward function should address the neurobiological state factors that participate to control generation of incentive salience.
Re‐evaluating the role of the orbitofrontal cortex in reward and reinforcement
Authors: Noonan M. P. , Kolling N. , Walton M. E. , Rushworth M. F. S.
Published: April 2012

The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value‐guided decision‐making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.
A theoretical account of cognitive effects in delay discounting
Authors: Kurth‐Nelson Zeb , Bickel Warren , Redish A. David
Published: April 2012

Although delay discounting, the attenuation of the value of future rewards, is a robust finding, the mechanism of discounting is not known. We propose a potential mechanism for delay discounting such that discounting emerges from a search process that is trying to determine what rewards will be available in the future. In this theory, the delay dependence of the discounting of future expected rewards arises from three assumptions. First, that the evaluation of outcomes involves a search process. Second, that the value is assigned to an outcome proportionally to how easy it is to find. Third, that outcomes that are less delayed are typically easier for the search process to find. By relaxing this third assumption (e.g. by assuming that episodically‐cued outcomes are easier to find), our model suggests that it is possible to dissociate discounting from delay. Our theory thereby explains the empirical result that discounting is slower to episodically‐imagined outcomes, because these outcomes are easier for the search process to find. Additionally, the theory explains why improving cognitive resources such as working memory slows discounting, by improving searches and thereby making rewards easier to find. The three assumptions outlined here are likely to be instantiated during deliberative decision‐making, but are unlikely in habitual decision‐making. We model two simple implementations of this theory and show that they unify empirical results about the role of cognitive function in delay discounting, and make new neural, behavioral, and pharmacological predictions.
Beyond simple reinforcement learning: the computational neurobiology of reward‐learning and valuation
Authors: O’Doherty John P.
Published: April 2012

Neural computational accounts of reward‐learning have been dominated by the hypothesis that dopamine neurons behave like a reward‐prediction error and thus facilitate reinforcement learning in striatal target neurons. While this framework is consistent with a lot of behavioral and neural evidence, this theory fails to account for a number of behavioral and neurobiological observations. In this special issue of EJN we feature a combination of theoretical and experimental papers highlighting some of the explanatory challenges faced by simple reinforcement‐learning models and describing some of the ways in which the framework is being extended in order to address these challenges.