bluuebunny/crossref_metadata_2025 huggingface dataset:
Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice
Authors: Li X.‐H. , Lin M.‐L. , Wang Z.‐L. , Wang P. , Tang H.‐H. , Lin Y.‐Y. , Li N. , Fang Q. , Wang R.
Published: March 2016

Background

Hemopressin was identified as an endogenous inverse agonist/antagonist of CB1 receptor, whereas VD‐hemopressin(α) [VD‐Hpα] and VD‐hemopressin(β) [VD‐Hpβ] were found as the novel endogenous peptidic agonists of cannabinoid receptors. As cannabinoids are potent modulators of gastrointestinal (GI) motility, our aim was to characterize the effects of hemopressin and related peptides on GI motility in vivo.

Methods

The responses of intracerebroventricular (i.c.v.) administration of the reference compound WIN55,212‐2, hemopressin, and related peptides to GI motility were investigated by measuring upper GI transit, colonic bead expulsion, and whole gut transit in mice.

Key Results

Central administration of the classical cannabinoid receptor agonist WIN55,212‐2 dose‐dependently slowed upper GI transit, colonic expulsion, and whole gut transit via CB1 receptor. Similarly, Hpα, VD‐Hpα, and VD‐Hpβ delayed upper GI transit and colonic expulsion after i.c.v. administration. At the high doses, Hpα and VD‐Hpβ inhibited whole gut transit, whereas VD‐Hpα had no effect on whole gut transit. In addition, the effects of these three peptides on GI transit were antagonized by the CB1 receptor selective antagonist AM251, but not by the CB2 receptor selective antagonist AM630.

Conclusion & Inferences

The endogenous cannabinoid peptide ligands hemopressin, VD‐Hpα, and VD‐Hpβ inhibited GI transit through the activation of CB1, but not CB2 cannabinoid receptors. The lower potencies of the hemopressin and related peptides in GI transit assays may be important for the future development of cannabinoid peptides as the therapeutic analgesics with limited GI side effects.
Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome
Authors: Jarrett M. E. , Han C. J. , Cain K. C. , Burr R. L. , Shulman R. J. , Barney P. G. , Naliboff B. D. , Zia J. , Heitkemper M. M.
Published: March 2016

Background

Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity.

Methods

Women between ages 18–45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4‐week symptom diary and had a 12‐h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid‐follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test.

Key Results

As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS‐diarrhea [IBS‐D], IBS‐constipation plus mixed [IBS‐CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS‐CM group than the IBS‐D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS‐CM group was higher than the IBS‐D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group.

Conclusions & Inferences

Despite similar levels of abdominal pain in IBS, the IBS‐CM group demonstrated greater sensitivity to both thermal and visceral testing procedures.
Maxillary tuberosity fracture and ophthalmologic complications following removal of maxillary third molar
Authors: Baba J. , Iwai T. , Endo H. , Aoki N. , Tohnai I.
Published: March 2016

Third molar removal is one of the most common procedures performed by dentists and oral surgeons. Removal of maxillary third molar is associated with a lower rate of complication compared to the mandible, and maxillary tuberosity fracture or ophthalmologic complications after removal of maxillary third molar are very rare. We report maxillary tuberosity fracture and ophthalmologic complications following removal of maxillary third molar. A 35‐year‐old female underwent removal of left maxillary third molar at private dental clinic. Following the complete extraction, excessive haemorrhage occurred and maxillary tuberosity fracture was seen and the patient was brought by ambulance to our hospital. The bleeding was controlled by vacuum‐formed splint and nasal packing. Computed tomography revealed that lateral maxillary tuberosity and posterior wall of the maxillary sinus was defect and there was a slight intraorbital haematoma via the inferior orbital fissure as well as with extension in the maxillary sinus and adjacent spaces such as buccal, masticator, pterygomaxillary and infratemporal spaces. Because an ophthalmologist noted only slight diplopia in lateral gaze without abnormal signs in other examinations and nasal and oral bleeding were controlled, the surgical treatment was not required. The patient was immediately hospitalised for close observation. Intravenous antibiotics and steroids were administered. Because swelling of the cheek and buccal mucosa was gradually decreasing without further haemorrhage, the patient was discharged 4 days after the extraction. The diplopia was recovered completely 11 days after the extraction.
Validated Measures of Illness Perception and Behavior in People with Knee Pain and Knee Osteoarthritis: A Scoping Review
Authors: Hamilton Clayon B. , Wong Ming‐Kin , Gignac Monique A.M. , Davis Aileen M. , Chesworth Bert M.
Published: March 2016

Objective

To identify validated measures that capture illness perception and behavior and have been used to assess people who have knee pain/osteoarthritis.

Methods

A scoping review was performed. Nine electronic databases were searched for records from inception through April 19, 2015. Search terms included illness perception, illness behavior, knee, pain, osteoarthritis, and their related terms. This review included English language publications of primary data on people with knee pain/osteoarthritis who were assessed with validated measures capturing any of 4 components of illness perception and behavior: monitor body, define and interpret symptoms, take remedial action, and utilize sources of help. Seventy‐one publications included relevant measures. Two reviewers independently coded and analyzed each relevant measure within the 4 components.

Results

Sixteen measures were identified that capture components of illness perception and behavior in the target population. These measures were originally developed to capture constructs that include coping strategies/skills/styles, illness belief, illness perception, self‐efficacy, and pain behavior. Coding results indicated that 5, 11, 12, and 5 of these measures included the monitor body, define and interpret symptoms, take remedial action, and utilize sources of help components, respectively.

Conclusions

Several validated measures were interpreted as capturing some components, and only 1 measure was interpreted as capturing all of the components of illness perception and behavior in the target population. A measure that comprehensively captures illness perception and behavior could be valuable for informing and evaluating therapy for patients along a continuum of symptomatic knee osteoarthritis.
The restorer gene for soybean M‐type cytoplasmic male sterility, Rf‐m, is located in a PPR gene‐rich region on chromosome 16
Authors: Wang Dagang , Zhang Lei , Li Jiekun , Hu Guoyu , Wu Qian , Jiang Haiyan , Huang Zhiping
Published: March 2016

Over the past decade, M‐type cytoplasmic male sterility (CMS) line W931A and a variety of restorer lines have been exploited for the release of hybrid seeds in soybean (Glycine max). However, the identities of restorer genes in the nuclei of soybean restorer lines are still unclear. In this study, we analysed the inheritance pattern of restorer locus Rf‐m from restorer line WR016 and constructed a high‐resolution map of this locus. Results showed that Rf‐m in WR016 is a monogenic dominant gene located within a 162.4‐kb region on chromosome 16, which is flanked on each side by new developed simple sequence repeat (SSR) markers GmSSR1602 and GmSSR1610 at a distance of 0.11 and 0.25 cM, respectively. Nineteen open reading frames (ORFs) were predicted in this region. Of these, seven genes arranged in tandem on chromosome 16 encode pentatricopeptide repeat (PPR) proteins, which is similar to other reported restorer loci in plants. These results lay a solid foundation for map‐based cloning of the Rf‐m gene and will be helpful for marker‐assisted selection of elite CMS restorer lines.
In situmicroscopy reveals reversible cell wall swelling in kelp sieve tubes: one mechanism for turgor generation and flow control?
Authors: Knoblauch Jan , Tepler Drobnitch Sarah , Peters Winfried S. , Knoblauch Michael
Published: March 2016

Kelps, brown algae (Phaeophyceae) of the order Laminariales, possess sieve tubes for the symplasmic long‐distance transport of photoassimilates that are evolutionarily unrelated but structurally similar to the tubes in the phloem of vascular plants. We visualized sieve tube structure and wound responses in fully functional, intact Bull Kelp (Nereocystis luetkeana[K. Mertens] Postels & Ruprecht 1840). In injured tubes, apparent slime plugs formed but were unlikely to cause sieve tube occlusion as they assembled at the downstream side of sieve plates. Cell walls expanded massively in the radial direction, reducing the volume of the wounded sieve elements by up to 90%. Ultrastructural examination showed that a layer of the immediate cell wall characterized by circumferential cellulose fibrils was responsible for swelling and suggested that alginates, abundant gelatinous polymers of the cell wall matrix, were involved. Wall swelling was rapid, reversible and depended on intracellular pressure, as demonstrated by pressure‐injection of silicon oil. Our results revive the concept of turgor generation and buffering by swelling cell walls, which had fallen into oblivion over the last century. Because sieve tube transport is pressure‐driven and controlled physically by tube diameter, a regulatory role of wall swelling in photoassimilate distribution is implied in kelps.
Association between electroencephalographic modulation, psychotic‐like experiences and cognitive performance in the general population
Authors: Gomez‐Pilar Javier , Martín‐Santiago Oscar , Suazo Vanessa , de Azua Sonia Ruiz , Haidar Mahmoud Karim , Gallardo Ricardo , Poza Jesús , Hornero Roberto , Molina Vicente
Published: March 2016

Aim

An association between deficit of electroencephalographic (EEG) modulation during an oddball task and psychotic symptoms has been described in clinical samples, in agreement with the proposed role of altered salience in psychosis. To discard the possible influence of medication, the relation between psychotic‐like experiences (PLE) and EEG modulation in the general population was explored.

Methods

EEG and PLE were assessed in 194 healthy subjects during a P300 paradigm. EEG modulation was assessed as changes from pre‐stimulus to response windows in spectral entropy (SE; a measurement of signal irregularity), median frequency (MF; a quantifier of the frequency distribution of oscillatory activity) and theta, alpha, beta‐1, beta‐2 and gamma relative power (RP; a summary of the distribution of spectral components).

Results

A significant widespread decrease in SE and MF from baseline to response was found, with a significant increase in RP for theta and a decrease for higher frequency bands, supporting an increase in EEG regularity and a slowing of brain oscillations during the response. Furthermore, a significant association was found between SE modulation and distress of negative PLE, as well as between verbal memory and RP modulation for beta‐1. Performance in verbal fluency was associated with the increase in theta RP during the response.

Conclusion

EEG irregularity of healthy subjects decreased at the expense of a larger contribution of theta RP and a decreased contribution of fast frequency bands. Subjects with smaller modulation showed poorer cognitive scores and greater distress of negative PLE.
A 10‐year follow‐up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole‐genome sequencing
Authors: Ono Ryusuke , Masaki Taro , Mayca Pozo Franklin , Nakazawa Yuka , Swagemakers Sigrid M. A. , Nakano Eiji , Sakai Wataru , Takeuchi Seiji , Kanda Fumio , Ogi Tomoo , van der Spek Peter J. , Sugasawa Kaoru , Nishigori Chikako
Published: March 2016

Background

Most patients with xeroderma pigmentosum complementation group D (XP‐D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP‐D patients are attributed partly to a predominant mutation in ERCC2, and the allele frequency of S541R is highest in Japan.

Methods

We diagnosed a child with mild case of XP‐D by the evaluation of DNA repair activity and whole‐genome sequencing, and followed her ten years.

Results

Skin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm2, which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post‐UV unscheduled DNA synthesis was 20.4%, and post‐UV recovery of RNA synthesis was 58% of non‐irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* in ERCC2: then, patient was diagnosed with XP‐D. Y197* has not been described before.

Conclusion

Her mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation of ERCC2 among Japanese XP‐D patients, as it was identified most frequently in Japanese XP‐D patients and it has not been found elsewhere outside Japan.
Epistemic Angst
Authors: Pritchard Duncan
Published: March 2016

Support is canvassed for a novel solution to the sceptical problem regarding our knowledge of the external world. Key to this solution is the claim that what initially looks like a single problem is in fact two logically distinct problems. In particular, there are two putative sceptical paradoxes in play here, which each trade on distinctive epistemological theses. It is argued that the ideal solution to radical scepticism would thus be a biscopic proposal—viz., a two‐pronged, integrated, undercutting treatment of both putative sceptical paradoxes. A particular biscopic proposal is then explored which brings together two apparently opposing anti‐sceptical theses: he Wittgensteinian account of the structure of rational evaluation and epistemological disjunctivism. It is argued that each proposal enables us to gain a purchase on one, but only one, aspect of the two‐sided sceptical problem. Furthermore, it is argued that these proposals are not only compatible positions, but also mutually supporting and advanced in the same undercutting spirit. A potential cure is thus offered for epistemic angst.
Pathogen‐induced conditioning of the primary xylem vessels – a prerequisite for the formation of bacterial emboli by Pectobacterium atrosepticum
Authors: Gorshkov V. Y. , Daminova A. G. , Mikshina P. V. , Petrova O. E. , Ageeva M. V. , Salnikov V. V. , Gorshkova T. A. , Gogolev Y. V.
Published: March 2016

Representatives of Pectobacterium genus are some of the most harmful phytopathogens in the world. In the present study, we have elucidated novel aspects of plant–Pectobacterium atrosepticum interactions. This bacterium was recently demonstrated to form specific ‘multicellular’ structures – bacterial emboli in the xylem vessels of infected plants. In our work, we showed that the process of formation of these structures includes the pathogen‐induced reactions of the plant. The colonisation of the plant by P. atrosepticum is coupled with the release of a pectic polysaccharide, rhamnogalacturonan I, into the vessel lumen from the plant cell wall. This polysaccharide gives rise to a gel that serves as a matrix for bacterial emboli. P. atrosepticum‐caused infection involves an increase of reactive oxygen species (ROS) levels in the vessels, creating the conditions for the scission of polysaccharides and modification of plant cell wall composition. Both the release of rhamnogalacturonan I and the increase in ROS precede colonisation of the vessels by bacteria and occur only in the primary xylem vessels, the same as the subsequent formation of bacterial emboli. Since the appearance of rhamnogalacturonan I and increase in ROS levels do not hamper the bacterial cells and form a basis for the assembly of bacterial emboli, these reactions may be regarded as part of the susceptible response of the plant. Bacterial emboli thus represent the products of host–pathogen integration, since the formation of these structures requires the action of both partners.
Network Neutrality Versus Paid Prioritization: Analyzing the Impact on Content Innovation
Authors: Guo Hong , Easley Robert F.
Published: March 2016

We examine the link between network neutrality (NN) and content innovation on the Internet by comparing the impact of NN and packet discrimination (PD) regimes on content innovation. We do this in the context of a two‐sided market model that simultaneously considers content provider (CP) and consumer decisions concerning market entry and participation while taking into account consumers’ response to network congestion. We find that content innovation flourishes under NN to a greater degree than under PD due to two effects we uncover: the generation of what we call a pro bono innovation zone in which CPs are able to enter the market without contributing to network provider profits; and the cross‐side congestion effect, a negative network externality wherein higher broadband market coverage levels result in greater congestion for CPs, and increased content results in greater congestion for consumers, taking into account consumers’ strategic response to network congestion. These results have important implications for current public policy debates regarding the Federal Communications Commission's Open Internet Rules.
Designing Supply Contracts Considering Profit Targets and Risk
Authors: Deng Shiming , Yano Candace Arai
Published: March 2016

Managers at all stages of a supply chain are concerned about meeting profit targets. We study contract design for a buyer–supplier supply chain, with each party maximizing expected profit subject to a chance constraint on meeting his respective profit target. We derive the optimal contract form (across all contract types) with randomized and deterministic payments. The best contract has the property that, if the chance constraints are binding, at most one party fails to satisfy his profit target for any given demand realization. This implies that “least risk sharing,”that is, minimizing the probability of outcomes for which both parties fail to achieve their profit targets, is optimal, contrary to the usual expectations of “risk sharing.” We show that an optimal contract can possess only two of the following three properties simultaneously: (i) supply chain coordination, (ii) truth‐telling, and (iii) non‐randomized payments. We discuss methods to mitigate the consequent implementation challenges. We also derive the optimal contract form when chance constraints are incorporated into several simpler and easier‐to‐implement contracts. From a numerical study, we find that an incremental returns contract (in which the marginal rebate rate depends on the return quantity) performs quite well across a relatively broad range of conditions.
Humanitarian Funding in a Multi‐Donor Market with Donation Uncertainty
Authors: Aflaki Arian , Pedraza‐Martinez Alfonso J.
Published: March 2016

This study analyzes the trade‐off between funding strategies and operational performance in humanitarian operations. If a Humanitarian Organization (HO) offers donors the option of earmarking their donations, HO should expect an increase in total donations. However, earmarking creates constraints in resource allocation that negatively affect HO's operational performance. We study this trade‐off from the perspective of a single HO that maximizes its expected utility as a function of total donations and operational performance. HO implements disaster response and development programs and it operates in a multi‐donor market with donation uncertainty. Using a model inspired by Scarf's minimax approach and the newsvendor framework, we analyze the strategic interaction between HO and its donors. The numerical section is based on real data from 15 disasters during the period 2012–2013. We find that poor operational performance has a larger effect on HO's utility function when donors are more uncertain about HO's expected needs for disaster response. Interestingly, increasing the public awareness of development programs helps HO to get more non‐earmarked donations for disaster response. Increasing non‐earmarked donations improves HO's operational efficiency, which mitigates the impact of donation uncertainty on HO's utility function.
A stress‐associated NAC transcription factor (SlNAC35) from tomato plays a positive role in biotic and abiotic stresses
Authors: Wang Guodong , Zhang Song , Ma Xiaocui , Wang Yong , Kong Fanying , Meng Qingwei
Published: March 2016

The NAC transcription factor family participates in responses to various kinds of environmental stimuli in plants. Responses of NAC genes to abiotic stresses have been widely studied, but their functions in response to biotic stress are little reported in plants, especially in crops. In the present study, we examined the functions of a novel tomato (Solanum lycopersicum) NAC protein (SlNAC35) in abiotic and biotic stress resistance by using transgenic tobacco. Expression analysis found that SlNAC35 expression was induced by drought stress, salt stress, bacterial pathogen, and signaling molecules, suggesting its involvement in plant responses to biotic and abiotic stimuli. Moreover, transgenic lines exhibited a greater number of lateral roots and longer root length compared with Vec lines (empty vector lines) after drought and salt treatment. These results indicate that overexpression of SlNAC35 promoted root growth and development under drought and salt stresses. Higher expressions of NtARF1, NtARF2 and NtARF8 were observed under drought and salt stresses in transgenic lines, suggesting that overexpression of SlNAC35 promoted growth and development of roots in transgenic lines possibly by involving auxin signaling and by regulating NtARF expression. In addition, SlNAC35 overexpression improved resistance to bacterial pathogen in transgenic tobacco, and reactive oxygen species may be in the upstream of salicylic acid (SA) signaling in transgenic tobacco during defense response.
The nursing role during end‐of‐life care in the intensive care unit related to the interaction between patient, family and professional: an integrative review
Authors: Noome Marijke , Beneken genaamd Kolmer Deirdre M. , van Leeuwen Evert , Dijkstra Boukje M. , Vloet Lilian C. M.
Published: March 2016

Aim

The aim of this study was to explore how intensive care unit (ICU) nurses describe their role during End‐of‐Life Care (EOLC) in the ICU, related to the interaction between patient, family and professionals (care triad).

Method

Three electronic databases, PubMed, CINAHL and EMBASE, and reference lists of included studies were searched for studies in English, Dutch or German between January 2002 and August 2015. Studies were included if they presented data about EOLC in the adult ICU, and the role of ICU nurses around EOLC. Quantitative and qualitative studies and opinion articles were extracted. Inductive content analysis was carried out to analyse and categorise the data.

Results

Twenty studies were included. Four categories emerged: care for the ICU patient, care for the family, environmental aspects of EOLC and organisational aspects of EOLC. Regarding the care triad, a gap exists between theoretical models and the actual care provided by ICU nurses during EOLC. The relational aspect of care, like aimed with care triad, is absent.

Conclusion

The literature clearly indicates that the role of ICU nurses concerns care for the patient, family and environment. It described which care should be given, but it remains unclear how care should be given (attitude). Therefore, it is difficult for ICU nurses to provide this care. Further, it seems that care provided to family mainly consists of giving advice on how to care for the patient; care for family members themselves was only mentioned in a few studies. Therefore, it seems that family does not always receive adequate care yet, which may be helpful in preventing problems like depression, anxiety or post‐traumatic stress disorder. It can be concluded that it is important for ICU nurses to be aware of the existing relationships; however, comparing the literature, care triad does not appear to be reached.
Electroencephalographic study showing that tactile stimulation by fabrics of different qualities elicit graded event‐related potentials
Authors: Hoefer D. , Handel M. , Müller K.‐M. , Hammer T. R.
Published: March 2016

Background/purpose

Neurophysiologic data on reactions of the human brain towards tactile stimuli evoked by fabrics moved on the skin are scarce. Furthermore, evaluation of fabrics' pleasantness using questionnaires suffers subjective biases. That is why we used a 64‐channel electroencephalography (EEG) to objectively evaluate real‐time brain reactions to fabric–skin interactions.

Methods

Tactile stimuli were triggered by selected fabrics of different qualities, i.e. modal/polyamide single jersey, cotton double rib and a jute fabric, applied hidden to either the palm or forearm of 24 subjects via a custom‐made fabric‐to‐skin applicator called SOFIA. One‐way anova analysis was carried out to verify the EEG data.

Results

The modal/polyamide fabric applied to the forearm and palm led to slightly stronger emotional valence scores in the brain than the conventional or baseline fabric. Furthermore, the single jersey elicits significant higher event‐related potential (ERP) signals in all subjects when applied to the forearm, suggesting less distraction and better cognitive resources during the fabric/skin interaction. The brain thus reacts with instantaneous ERP to tactile stimulation of fabrics and is able to discriminate different qualities via implicit preferences.

Conclusion

The test procedure described here may be a tool to evaluate the fabric feel with the exclusion of subjective biases.
Discovery of HLA‐B*58:77, a novel HLA‐B*58 variant, in a Taiwanese blood donor
Authors: Yang K. L. , Hung J. H. , Lin P. Y.
Published: March 2016

One nucleotide substitution at residue 506 of HLA‐B*58:01:01:01 results in a novel allele, HLA‐B*58:77.
Early non‐invasive selection of patients at high risk of severe hepatitis C recurrence after liver transplantation
Authors: Crespo G. , Gambato M. , Millán O. , Casals G. , Ruiz P. , Londoño M.C. , Mira A. , Forns X. , Brunet M. , Jiménez W. , Navasa M.
Published: March 2016

Background

The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon (IFN)‐free regimens.

Methods

In a retrospective study with prospectively collected data, we investigated whether the use of several non‐invasive methods (fibrosis 4 index [FIB‐4], AST‐to‐platelets ratio index [APRI], enhanced liver fibrosis test [ELF], IFN‐γ‐inducible protein 10 [IP‐10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F ≥2) and/or portal hypertension (hepatic venous pressure gradient ≥6 mmHg) 12 months after transplant. Seventy‐two hepatitis C virus (HCV)‐infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study.

Results

The levels of all biomarkers were significantly higher in HCV‐infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB‐4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved.

Conclusions

Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non‐invasive methods.
Identification of multiple lipid genes with modifications in expression and sequence associated with the evolution of hydroxy fatty acid accumulation in Physaria fendleri
Authors: Horn Patrick J. , Liu Jinjie , Cocuron Jean‐Christophe , McGlew Kathleen , Thrower Nicholas A. , Larson Matt , Lu Chaofu , Alonso Ana P. , Ohlrogge John
Published: March 2016

Two Brassicaceae species, Physaria fendleri and Camelina sativa, are genetically very closely related to each other and to Arabidopsis thaliana. Physaria fendleri seeds contain over 50% hydroxy fatty acids (HFAs), while Camelina sativa and Arabidopsis do not accumulate HFAs. To better understand how plants evolved new biochemical pathways with the capacity to accumulate high levels of unusual fatty acids, transcript expression and protein sequences of developing seeds of Physaria fendleri, wild‐type Camelina sativa, and Camelina sativa expressing a castor bean (Ricinus communis) hydroxylase were analyzed. A number of potential evolutionary adaptations within lipid metabolism that probably enhance HFA production and accumulation in Physaria fendleri, and, in their absence, limit accumulation in transgenic tissues were revealed. These adaptations occurred in at least 20 genes within several lipid pathways from the onset of fatty acid synthesis and its regulation to the assembly of triacylglycerols. Lipid genes of Physaria fendleri appear to have co‐evolved through modulation of transcriptional abundances and alterations within protein sequences. Only a handful of genes showed evidence for sequence adaptation through gene duplication. Collectively, these evolutionary changes probably occurred to minimize deleterious effects of high HFA amounts and/or to enhance accumulation for physiological advantage. These results shed light on the evolution of pathways for novel fatty acid production in seeds, help explain some of the current limitations to accumulation of HFAs in transgenic plants, and may provide improved strategies for future engineering of their production.
The broadly effective recessive resistance gene xa5 of rice is a virulence effector‐dependent quantitative trait for bacterial blight
Authors: Huang Sheng , Antony Ginny , Li Ting , Liu Bo , Obasa Ken , Yang Bing , White Frank F.
Published: March 2016

Mutations in disease susceptibility (S) genes, here referred to as recessive resistance genes, have promise for providing broad durable resistance in crop species. However, few recessive disease resistance genes have been characterized. Here, we show that the broadly effective resistance gene xa5,for resistance to bacterial blight of rice (Oryza sativa), is dependent on the effector genes present in the pathogen. Specifically, the effectiveness of xa5 in preventing disease by strains of Xanthomonas oryzae pv. oryzae is dependent on major transcription activation‐like (TAL) effector genes, and correlates with reduced expression of the cognate S genes. xa5 is ineffective in preventing disease by strains containing the TAL effector gene pthXo1, which directs robust expression of the S gene OsSWEET11, a member of sucrose transporter gene family. Incompatibility is associated with major TAL effectors that target the known alternative S genes OsSWEET14 and OsSWEET13. Incompatibility is defeated by transfer of pthXo1 to otherwise xa5‐incompatible strains or by engineering a synthetic designer TAL effector to boost SWEET gene expression. In either case, compatible or incompatible, target gene expression and lesion formation are reduced in the presence of xa5. The results indicate that xa5 functions as a quantitative trait locus, dampening effector function, and, regardless of compatibility, target gene expression. Resistance is hypothesized to occur when S gene expression, and, by inference, sucrose leakage, falls below a threshold level.
Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale
Authors: Lovering Andrew T. , Lozo Mislav , Barak Otto , Davis James T. , Lojpur Mihajlo , Lozo Petar , Čaljkušić Krešimir , Dujić Željko
Published: March 2016

New Findings

What is the central question of this study?

Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension?

What is the main finding and its importance?

The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension.

The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses () and/or patent foramen ovale () could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty‐six subjects with CHF (New York Heart Association Classes I–III), with (+) or without (−) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s−1 (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s−1 (CHF PH−, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect and . Seventeen of 56 subjects with CHF (30%) had , but only four of 56 subjects with CHF had (7%), both similar to age‐ and sex‐matched control subjects. Mean arterial oxygen saturation () was lower in subjects with . Only CHF PH+ subjects with had arterial hypoxaemia (mean <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with . Significant was not present in either CHF PH+ or PH− subjects, suggesting that is not dependent on increased pulmonary pressure and does not contribute significantly to arterial hypoxaemia in older subjects with CHF. Given that was lower in all subjects with CHF who had compared with those without , a patent foramen ovale should be considered when determining potential causes of arterial hypoxaemia, because was present in 30% of these subjects.
Carotid body modulation in systolic heart failure from the clinical perspective
Authors: Niewinski Piotr
Published: March 2016

Augmented sensitivity of peripheral chemoreceptors (PChS) is a common finding in systolic heart failure (HF). It is related to lower left ventricle systolic function, higher plasma concentrations of natriuretic peptides, worse exercise tolerance and greater prevalence of atrial fibrillation compared to patients with normal PChS. The magnitude of ventilatory response to the activation of peripheral chemoreceptors is proportional to the level of heart rate (tachycardia) and blood pressure (hypertension) responses. All these responses can be measured non‐invasively in a safe and reproducible fashion using different methods employing either hypoxia or hypercapnia. Current interventions aimed at modulation of peripheral chemoreceptors in HF are focused on carotid bodies (CBs). There is a clear link between afferent signalling from CBs and sympathetic overactivity, which remains the priority target of modern HF treatment. However, CB modulation therapies may face several potential obstacles: (1) As evidenced by HF trials, an excessive inhibition of sympathetic system may be harmful. (2) Proximity of critical anatomical structures (important vessels and nerves) makes surgical and transcutaneous interventions on CB technically demanding. (3) Co‐existence of atherosclerosis in the area of carotid artery bifurcation increases the risk of central embolic events related to CB modulation. (4) The relative contribution of CBs vs. aortic bodies to sympathetic activation in HF patients is unclear. (5) Choosing optimal candidates for CB modulation from the population of HF patients may be problematic. (6) There is a risk of nocturnal hypoxia following CB ablation – mostly after bilateral procedures and in patients with concomitant obstructive sleep apnoea.

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A Nonautochthonous U.S. Strain of Vibrio parahaemolyticus Isolated from Chesapeake Bay Oysters Caused the Outbreak in Maryland in 2010
Authors: Haendiges Julie , Jones Jessica , Myers Robert A. , Mitchell Clifford S. , Butler Erin , Toro Magaly , Gonzalez-Escalona Narjol
Published: March 2016

In the summer of 2010,
Vibrio parahaemolyticus
caused an outbreak in Maryland linked to the consumption of oysters. Strains isolated from both stool and oyster samples were indistinguishable by pulsed-field gel electrophoresis (PFGE). However, the oysters contained other potentially pathogenic
V. parahaemolyticus
strains exhibiting different PFGE patterns. In order to assess the identity, genetic makeup, relatedness, and potential pathogenicity of the
V. parahaemolyticus
strains, we sequenced 11 such strains (2 clinical strains and 9 oyster strains). We analyzed these genomes by
in silico
multilocus sequence typing (MLST) and determined their phylogeny using a whole-genome MLST (wgMLST) analysis. Our
in silico
MLST analysis identified six different sequence types (STs) (ST8, ST676, ST810, ST811, ST34, and ST768), with both of the clinical and four of the oyster strains being identified as belonging to ST8. Using wgMLST, we showed that the ST8 strains from clinical and oyster samples were nearly indistinguishable and belonged to the same outbreak, confirming that local oysters were the source of the infections. The remaining oyster strains were genetically diverse, differing in >3,000 loci from the Maryland ST8 strains. eBURST analysis comparing these strains with strains of other STs available at the
V. parahaemolyticus
MLST website showed that the Maryland ST8 strains belonged to a clonal complex endemic to Asia. This indicates that the ST8 isolates from clinical and oyster sources were likely not endemic to Maryland. Finally, this study demonstrates the utility of whole-genome sequencing (WGS) and associated analyses for source-tracking investigations.

IMPORTANCE
Vibrio parahaemolyticus
is an important foodborne pathogen and the leading cause of bacterial infections in the United States associated with the consumption of seafood. In the summer of 2010,
Vibrio parahaemolyticus
caused an outbreak in Maryland linked to oyster consumption. Strains isolated from stool and oyster samples were indistinguishable by pulsed-field gel electrophoresis (PFGE). The oysters also contained other potentially pathogenic
V. parahaemolyticus
strains with different PFGE patterns. Since their identity, genetic makeup, relatedness, and potential pathogenicity were unknown, their genomes were determined by using next-generation sequencing. Whole-genome sequencing (WGS) analysis by whole-genome multilocus sequence typing (wgMLST) allowed (i) identification of clinical and oyster strains with matching PFGE profiles as belonging to ST8, (ii) determination of oyster strain diversity, and (iii) identification of the clinical strains as belonging to a clonal complex (CC) described only in Asia. Finally, WGS and associated analyses demonstrated their utility for trace-back investigations.
Construction of Nontoxigenic Mutants of Nonproteolytic Clostridium botulinum NCTC 11219 by Insertional Mutagenesis and Gene Replacement
Authors: Clauwers Charlien , Vanoirbeek Kristof , Delbrassinne Laurence , Michiels Chris W.
Published: March 2016

Group II nonproteolytic
Clostridium botulinum
(gIICb) strains are an important concern for the safety of minimally processed ready-to-eat foods, because they can grow and produce botulinum neurotoxin during refrigerated storage. The principles of control of gIICb by conventional food processing and preservation methods have been well investigated and translated into guidelines for the food industry; in contrast, the effectiveness of emerging processing and preservation techniques has been poorly documented. The reason is that experimental studies with
C. botulinum
are cumbersome because of biosafety and biosecurity concerns. In the present work, we report the construction of two nontoxigenic derivatives of the type E gIICb strain NCTC 11219. In the first strain, the botulinum toxin gene (
bont
/
E
) was insertionally inactivated with a retargeted intron using the ClosTron system. In the second strain,
bont
/
E
was exchanged for an erythromycin resistance gene using a new gene replacement strategy that makes use of
pyrE
as a bidirectional selection marker. Growth under optimal and stressed conditions, sporulation efficiency, and spore heat resistance of the mutants were unaltered, except for small differences in spore heat resistance at 70°C and in growth at 2.3% NaCl. The mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with gIICb. In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in gIICb and other clostridia.

IMPORTANCE
The nontoxigenic mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with psychrotrophic
Clostridium botulinum
. In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in clostridia.
Weekend effect in endovascular stroke treatment: do treatment decisions, procedural times, and outcome depend on time of admission?
Authors: Nikoubashman Omid , Probst Thomas , Schürmann Kolja , Othman Ahmed E , Matz Oliver , Brockmann Marc-Alexander , Müller Marguerite , Wiesmann Martin , Reich Arno
Published: March 2016

Background

Epidemiologic studies identified a ‘weekend effect’ or ‘out-of-hours effect’, which implies that procedural and clinical outcomes of patients with stroke, who are admitted out-of-hours, are less favorable than for patients admitted during working-hours.

Objective

To determine (1) whether our procedural times and clinical outcome were affected by an out-of-hours effect and (2) whether the decision in favor of, or against, endovascular stroke treatment (EST) depends on the time of admission.

Methods

Between February 2010 and January 2015, 6412 consecutive patients presenting with symptoms of acute ischemic stroke were evaluated for EST eligibility according to established local protocols and generally accepted consensus criteria, and dichotomized into working-hours and out-of-hours cohorts according to admission times. Within both groups, patients given EST were identified and the rate of treatment decision, procedural times, and clinical outcome were compared and analyzed.

Results

Clinical and radiological features of patients admitted in working-hours and out-of-hours did not differ significantly. Procedural times and clinical outcome were not affected by an out-of-hours effect (p≥0.054). 221/240 (92.1%) out-of-hours patients and 154/166 (92.8%) working-hours patients who were eligible for EST were transferred to the angiography suite for EST (p=0.798). The rationale not to treat patients who were eligible for EST did not differ between working-hours and out-of-hours admission (p=0.756).

Conclusions

It is possible to produce competitive procedural times regardless of the time of admission and to prevent a treatment decision bias when standard operating procedures are applied consistently.
Mentoring perception and academic performance: an Academic Health Science Centre survey
Authors: Athanasiou Thanos , Patel Vanash , Garas George , Ashrafian Hutan , Shetty Kunal , Sevdalis Nick , Panzarasa Pietro , Darzi Ara , Paroutis Sotirios
Published: March 2016

Purpose

To determine the association between professors' self-perception of mentoring skills and their academic performance.

Design

Two hundred and fifteen professors from Imperial College London, the first Academic Health Science Centre (AHSC) in the UK, were surveyed. The instrument adopted was the Mentorship Skills Self-Assessment Survey. Statement scores were aggregated to provide a score for each shared core, mentor-specific and mentee-specific skill. Univariate and multivariate regression analyses were used to evaluate their relationship with quantitative measures of academic performance (publications, citations and h-index).

Results

There were 104 professors that responded (response rate 48%). There were no statistically significant negative correlations between any mentoring statement and any performance measure. In contrast, several mentoring survey items were positively correlated with academic performance. The total survey score for frequency of application of mentoring skills had a statistically significant positive association with number of publications (B=0.012, SE=0.004, p=0.006), as did the frequency of acquiring mentors with number of citations (B=1.572, SE=0.702, p=0.030). Building trust and managing risks had a statistically significant positive association with h-index (B=0.941, SE=0.460, p=0.047 and B=0.613, SE=0.287, p=0.038, respectively).

Conclusions

This study supports the view that mentoring is associated with high academic performance. Importantly, it suggests that frequent use of mentoring skills and quality of mentoring have positive effects on academic performance. Formal mentoring programmes should be considered a fundamental part of all AHSCs’ configuration.
A study on pothole repair in Canada through questionnaire survey and laboratory evaluation of patching materials
Authors: Biswas Simita , Hashemian Leila , Hasanuzzaman Md. , Bayat Alireza
Published: March 2016

To investigate the current pothole repair practices in Canada, a questionnaire was distributed to Canadian transportation agencies. Outcomes showed a large portion of pothole repairs were performed during the summer season. Conventional cold mix, hot mix asphalt, Quality Pavement Repair, and Innovative Asphalt Repair were identified as commonly used patching materials. Moreover, the ‘throw-and-go’ method was the most common patching procedure and durability of repaired patches in winter was significantly less than repaired patches in summer. To evaluate the performance of patching materials, a laboratory testing program was conducted on cold mixes identified by the survey as being most commonly used. The laboratory results showed that curing time and temperature had a significant effect on strength gain for all cold mixes. Conventional cold mix showed higher stability and cohesion properties, while Quality Pavement Repair showed better moisture resistance and adhesion properties. All the cold mixes were sensitive to freeze–thaw damage.