bluuebunny/crossref_metadata_2025 huggingface dataset:
Mice find endophyte‐infected seed of tall fescue unpalatable – implications for the aviation industry
Authors: Finch S. C. , Pennell C. G. L. , Kerby J. W. F. , Cave V. M.
Published: October 2015

Bird strike is a significant problem for the aviation industry, caused in part by the attractiveness of the grass surrounding airports to birds. Endophyte‐infected grasses such as Avanex® have been shown to reduce bird populations at airports through the production of secondary metabolites. These metabolites are unpalatable to herbivorous, omnivorous and granivorous birds and are known to reduce insect densities, thereby making the sown areas less attractive to insectivorous birds. Raptors also provide a bird‐strike threat which could be reduced by controlling mouse populations around airports. In this study, the effect of endophyte‐infected seed on mouse feeding behaviour has been investigated. By performing a choice trial offering diets containing endophyte‐infected and endophyte‐free tall fescue seed, it was shown that endophyte‐infected seed was less palatable to mice (P < 0·001 in a 14‐d trial). Furthermore, when diet positions were reversed, mouse feeding behaviour was modified to again select endophyte‐free material (P < 0·001 over a further 14 d). This result shows that endophyte‐infected grasses could not only be used in the control of bird populations but they also have the potential to control mouse populations which in turn would decrease the number of raptors. This use of endophyte‐infected grasses in areas surrounding airport runways shows great promise for the aviation industry.
“Now Where Do We Go from Here?” Separateness, Integration, and Pluralism in Philadelphia
Authors: Zakai Sivan , Schneider Jack
Published: October 2015

Schooling for racial, ethnic, or religious minorities presents a challenge in the American democracy. Such groups, insofar as they are equal citizens, have the right to maintain their identities. As such, they have often used separate educational institutions to transmit distinct traditions, values, and mores. To the extent that the American experiment is a pluralistic one, the decision to remain different from dominant groups is a valid one.
The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex
Authors: Clark P. M. , Kunkel M. , Monos D. S.
Published: October 2015

Many genes related to innate and adaptive immunity reside within the major histocompatibility complex (MHC) and have been associated with a multitude of complex, immune‐related disorders. Despite years of genetic study, this region has seen few causative determinants discovered for immune‐mediated diseases. Reported associations have been curated in various databases including the Genetic Association Database, NCBI database of clinically relevant variants (ClinVar) and the Human Gene Mutation Database and together capture genetic associations and annotated pathogenic loci within the MHC and across the genome for a variety of complex, immune‐mediated diseases. A review of these three distinct databases reveals disparate annotations between associated genes and pathogenic loci, alluding to the polygenic, multifactorial nature of immune‐mediated diseases and the pleiotropic character of genes within the MHC. The technical limitations and inherent biases imposed by current approaches and technologies in studying the MHC create a strong case for the need to perform targeted deep sequencing of the MHC and other immunologically relevant loci in order to fully elucidate and study the causative elements of complex immune‐mediated diseases.
Expression of activation‐induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti‐pneumococcal B1a cells
Authors: Yamamoto Natsuo , Kerfoot Steven M. , Hutchinson Andrew T. , Dela Cruz Charles S. , Nakazawa Naomi , Szczepanik Marian , Majewska‐Szczepanik Monika , Nazimek Katarzyna , Ohana Noboru , Bryniarski Krzysztof , Mori Tsutomu , Muramatsu Masamichi , Kanemitsu Keiji , Askenase Philip W.
Published: October 2015

We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation‐induced cytidine deaminase (AID−/−), or invariant natural killer T (iNKT) cells (Jα18−/−), or interleukin‐13 (IL‐13−/−) had impaired early clearance of pneumococci in the lung, compared with wild‐type mice. In contrast, AID−/− mice adoptively transferred with AID+/+ B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity‐like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen‐specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti‐pneumococcal B1a cell initiating response, probably through early production of IL‐13, given that IL‐13−/− mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID‐dependent subset.
Interleukin‐23 (IL‐23), independent of IL‐17 and IL‐22, drives neutrophil recruitment and innate inflammation during Clostridium difficile colitis in mice
Authors: McDermott Andrew J. , Falkowski Nicole R. , McDonald Roderick A. , Pandit Chinmay R. , Young Vincent B. , Huffnagle Gary B.
Published: October 2015

Our objective was to determine the role of the inflammatory cytokine interleukin‐23 (IL‐23) in promoting neutrophil recruitment, inflammatory cytokine expression and intestinal histopathology in response to Clostridium difficile infection. Wild‐type (WT) and p19−/− (IL‐23KO) mice were pre‐treated with cefoperazone in their drinking water for 5 days, and after a 2‐day recovery period were challenged with spores from C. difficile strain VPI 10463. Interleukin‐23 deficiency was associated with significant defects in both the recruitment of CD11bHigh Ly6GHigh neutrophils to the colon and the expression of neutrophil chemoattractants and stabilization factors including Cxcl1, Cxcl2, Ccl3 and Csf3 within the colonic mucosa as compared with WT animals. Furthermore, the expression of inflammatory cytokines including Il33, Tnf and Il6 was significantly reduced in IL‐23‐deficient animals. There was also a trend towards less severe colonic histopathology in the absence of IL‐23. The induction of Il17a and Il22 was also significantly abrogated in IL‐23KO mice. Inflammatory cytokine expression and neutrophilic inflammation were not reduced in IL‐17a‐deficient mice or in mice treated with anti‐IL‐22 depleting monoclonal antibody. However, induction of RegIIIg was significantly reduced in animals treated with anti‐IL‐22 antibody. Taken together, these data indicate that IL‐23, but not IL‐17a or IL‐22, promotes neutrophil recruitment and inflammatory cytokine and chemokine expression in the colon in response to C. difficile infection.
Macrophage‐derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant
Authors: Shakya Akhilesh Kumar , Kumar Ashok , Holmdahl Rikard , Nandakumar Kutty Selva
Published: October 2015

Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well‐balanced polymer, poly‐N‐isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly‐N‐isopropylacrylamide‐co‐poly‐N‐tertbutylacrylamide and poly‐N‐tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly‐N‐tertbutylacrylamide induced arthritis, especially in Ncf1‐deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm‐CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo‐responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events.
Programmed DNA breaks in lymphoid cells: repair mechanisms and consequences in human disease
Authors: Prochazkova Jana , Loizou Joanna I.
Published: October 2015

In recent years, several novel congenital human disorders have been described with defects in lymphoid B‐cell and T‐cell functions that arise due to mutations in known and/or novel components of DNA repair and damage response pathways. Examples include impaired DNA double‐strand break repair, as well as compromised DNA damage‐induced signal transduction, including phosphorylation and ubiquitination. These disorders reinforce the importance of genome stability pathways in the development of lymphoid cells in humans. Furthermore, these conditions inform our knowledge of the biology of the mechanisms of genome stability and in some cases may provide potential routes to help exploit these pathways therapeutically. Here we review the mechanisms that repair programmed DNA lesions that occur during B‐cell and T‐cell development, as well as human diseases that arise through defects in these pathways.
Genetic characterisation of influenza C viruses detected in Singapore in 2006
Authors: Ting Pei‐jun , Seah Shirley Gek‐Kheng , Lim Elizabeth Ai‐Sim , Liaw Jasper Chin‐Wen , Boon‐Huan Tan
Published: October 2015

In an earlier study on respiratory infections in Singapore military recruits, four influenza C virus (FLUCV) infections were detected out of the 1354 samples collected. All four isolates were detected in 2006, and their whole genome was completely sequenced and analysed. Phylogenetic analysis of the hemagglutinin esterase fusion (HEF) gene revealed that all four Singapore isolates belonged to the C/Japan‐Kanagawa/1/76‐related lineage. However, the genes of the four FLUCV isolates had origins from several different lineages, and the genome composition resembles that of the C/Japan‐Miyagi/9/96‐like strains that had been circulating in Japan between 1996 and 2000.
Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation Using a Circular Multipolar Ablation Catheter: Safety and Efficacy Using Low‐Power Settings
Authors: BURRI HARAN , PARK CHAN‐IL , POKU NANA , GIRAUDET PHILIPPE , STETTLER CARINE , ZIMMERMANN MARC
Published: October 2015

Low‐Power Ablation of AF Using the nMARQ Catheter

Introduction

The circular irrigated decapolar nMARQ ablation catheter designed for treating atrial fibrillation (AF) has recently been recalled following two deaths due to esoatrial fistula. Injury to the esophagus has been previously reported in up to 50% of patients using 20–25 W unipolar radiofrequency (RF) energy. Low power of 15 W has been proposed to prevent this complication, but the efficacy of this strategy to avoid AF recurrence is unknown.

Methods and Results

Consecutive patients with drug‐refractory, symptomatic AF were included. Under electroanatomical navigation, the nMARQ catheter was used to isolate all PVs by applying 15 W of unipolar RF simultaneously from up to 10 poles during 40 seconds. Multiple applications were used for each vein, until isolation was achieved. Follow‐up was performed after a 2‐month blanking period. A total of 50 patients (37 males, age 58 ± 10 years) were included. All PVs were acutely isolated without requiring touch‐up by conventional ablation catheters. Pericardial effusion occurred in two patients, of whom one required periocardiocentesis. Right phrenic nerve palsy occurred in another patient, which partially resolved. There were no cases of esophageal fistula or stroke. After a follow‐up of 15±4 months, AF recurred in 27/50 (54%) patients.

Conclusion

The recurrence rate of AF with 15 W unipolar applications is high. Despite use of low power, complications such as pericardial effusion and phrenic nerve palsy may occur.
Plasma Parathyroid Hormone Is Independently Related to Nocturnal Blood Pressure in Hypertensive Patients: The Styrian Hypertension Study
Authors: Verheyen Nicolas D. , Kienreich Katharina , Gaksch Martin , van Ballegooijen Adriana J. , Grübler Martin R. , Hartaigh Briain Ó. , Schmid Johannes , Fahrleitner‐Pammer Astrid , Kraigher‐Krainer Elisabeth , Colantonio Caterina , Belyavskiy Evgeny , Treiber Gerlies , Catena Cristiana , Brussee Helmut , Pieske Burkert , März Winfried , Tomaschitz Andreas , Pilz Stefan
Published: October 2015

High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24‐hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross‐sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39–61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH‐modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β‐coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies.
The Impact of Using Different Methods to Assess Completeness of 24‐Hour Urine Collection on Estimating Dietary Sodium
Authors: Wielgosz Andreas , Robinson Christopher , Mao Yang , Jiang Ying , Campbell Norm R. C. , Muthuri Stella , Morrison Howard
Published: October 2015

The standard for population‐based surveillance of dietary sodium intake is 24‐hour urine testing; however, this may be affected by incomplete urine collection. The impact of different indirect methods of assessing completeness of collection on estimated sodium ingestion has not been established. The authors enlisted 507 participants from an existing community study in 2009 to collect 24‐hour urine samples. Several methods of assessing completeness of urine collection were tested. Mean sodium intake varied between 3648 mg/24 h and 7210 mg/24 h depending on the method used. Excluding urine samples collected for longer or shorter than 24 hours increased the estimated urine sodium excretion, even when corrections for the variation in timed collections were applied. Until an accurate method of indirectly assessing completeness of urine collection is identified, the gold standard of administering para‐aminobenzoic acid is recommended. Efforts to ensure participants collect complete urine samples are also warranted.
Banking on Bonds: The New Links Between States and Markets
Authors: Gabor Daniela , Ban Cornel
Published: October 2015

This article examines a neglected structural transformation in European finance: the growing importance of government debt as collateral for Europe's repo markets, where banks borrow cash against collateral. Seduced by the promises of repo market‐driven financial integration, the EU institutions and Member States encouraged private finance to generate its own architecture for the European repo market in the early years of the euro, sidelining known problems about systemic fragilities. These fragilities materialized after Lehman Brothers’ collapse and were exacerbated by the ECB's collateral policies. The European sovereign debt crisis shows that governments, just like private asset issuers, can rapidly become vulnerable to repo pro‐cyclicality and collateral crises.
Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure
Authors: Yin Guo Qing , Zhong Bei
Published: October 2015

Background and Aim

In China, inappropriate therapies with nucleos(t)ide analogues (NA) have induced hepatitis B virus resistance, combination therapy with nucleoside and nucleotide (ComTNsNt) failure, or multi‐drug resistant mutations. However, the efficacy of combination therapy with entecavir plus tenofovir for ComTNsNt failure is limited. In the current study, the regimens of interferon‐α (IFN‐α) therapy, switching from NAs to IFN‐α, and subsequent re‐treatment with IFN‐α were applied to treat ComTNsNt failure. We further evaluated the efficacy of this therapy.

Methods

Eleven patients with ComTNsNt failure were enrolled in this study. Nine subjects (9/11) received IFN‐α switching therapy. Combination therapy with IFN‐α and ComTNsNt was administered in the first 4 weeks. Then, ComTNsNt was discontinued at the end of Week 4, and IFN‐α monotherapy was continued for 6 months. Two (2/11) patients discontinued ComTNsNt without receiving IFN‐α treatment. All 11 patients received the first re‐treatment of IFN‐α when they experienced hepatitis relapses after the withdrawal of IFN‐α or ComTNsNt. Six (6/11) patients received a second re‐treatment of IFN‐α. Follow up was conducted after IFN‐α therapy in all 11 patients.

Results

Two patients (2/9) receiving IFN‐α switching therapy experienced alanine aminotransferase (ALT) flare. In contrast, the two patients without IFN‐α switching therapy experienced ALT flare. Multiple re‐treatments with IFN‐α resulted in a sustained response.

Conclusions

Interferon‐α switching therapy and IFN‐α re‐treatment might be applied for treatment of ComTNsNt failure. IFN‐α switching therapy resulted in safe ComTNsNt cessation, and IFN‐α re‐treatment induced a sustained response of IFN‐α in all patients. This IFN‐α treatment is an optional treatment for ComTNsNt failure.
Doppler tissue perfusion parameters in recognizing pancreatic malignant tumors
Authors: Dyrla Przemysław , Lubas Arkadiusz , Gil Jerzy , Niemczyk Stanisław
Published: October 2015

Background

Histopathology, radiological imaging methods with the administration of contrast agents are efficient to differentiate focal lesions of the pancreas. Invasiveness, contrast toxicity, and limited accessibility ameliorate their application. Noninvasive and contrast‐agent‐free method could improve diagnostics and accelerate treatment.

Aims

The aim of the study is to evaluate the diagnostic properties of ultrasound parameters of organ perfusion in the detection of malignant tumors of the pancreas.

Methods

Thirty‐six patients with a focal lesion of the pancreas underwent endosonography with color flow imaging and biopsy for histological evaluation. Five patients were excluded because of the absence of the Doppler signal in pancreatic lesion. In the dynamic tissue perfusion measurement (DTPM) means of flow velocity (FV), resistive index, pulsatility index, and perfusion relief intensity (PR) were estimated.

Results

In the group with malignant tumors FV was significantly lower compared with the group with inflammatory changes. In receiver operating characteristic (ROC) analysis FV below the optimal cut‐off point of 2.382 cm/s identified patients with malignant lesions with a sensitivity of 92% and specificity of 90%. In the group with malignant tumors significantly lower values of PR in all considered percentiles were observed. Based on the ROC analysis in the group with solid tumors, it was found that PR25 ≤ 0.057 allowed to recognize malignancies with a sensitivity of 100% and specificity of 80%, and in the groups with solid and cystic tumors with a sensitivity of 100% and specificity of 79%.

Conclusions

FV and PR intensity derived from DTPM are reliable markers in recognition of pancreatic malignant masses.
Caffeine prevents antihyperalgesic effect of gabapentin in an animal model of CRPS‐I: evidence for the involvement of spinal adenosine A1 receptor
Authors: Martins Daniel F. , Prado Marcos R. B. , Daruge‐Neto Eduardo , Batisti Ana P. , Emer Aline A. , Mazzardo‐Martins Leidiane , Santos Adair R. S. , Piovezan Anna P.
Published: October 2015

This study was designed to determine whether 3 weeks of gabapentin treatment is effective in alleviating neuropathic pain‐like behavior in animal models of complex regional pain syndrome type‐I and partial sciatic nerve ligation (PSNL). We investigated the contribution of adenosine subtypes to the antihyperalgesic effect of gabapentin by examining the effect of caffeine, a non‐selective adenosine A1 and A2 receptor antagonist or 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX), a selective adenosine A1 subtype receptor antagonist on this effect. Neuropathic pain was produced by unilateral prolonged hind paw ischemia and reperfusion (I/R) or PSNL procedures which resulted in stimulus‐evoked mechanical hyperalgesia. After procedures, animals received gabapentin (10, 30, or 100 mg/kg intraperitoneal, respectively), caffeine (10 mg/kg intraperitoneal or 150 nmol intrathecally) or DPCPX (3 µg intrathecally) alone or in combination. Mice were tested for tactile mechanical hyperalgesia at 1, 2, and 3 weeks following procedures. Gabapentin produced dose‐related inhibition of mechanical hyperalgesia over a 3‐week period, and this effect was blocked by concomitant caffeine or DPCPX administration 1 week after injuries. The results of this study demonstrated that the mechanism through which gabapentin produces its effect may involve the activation of adenosine A1 subtype receptor.
Diagnostic value of plasma lysophosphatidic acid levels in ovarian cancer patients: A case–control study and updated meta‐analysis
Authors: Cao Liyan , Zhang Yunjie , Fu Zhanzhao , Dong Lixin , Yang Sen , Meng Wei , Li Yiyang , Zhang Wenchao , Zhang Jialing , Zheng Changjun , Zhu He , Fan Limei
Published: October 2015

Aim

We investigated whether plasma levels of lysophosphatidic acid (LPA) could serve as a diagnostic indicator for assessing disease progression in ovarian cancer (OC) patients.

Material and Methods

In this study, we enrolled 98 patients with OC, 70 patients with benign ovarian tumors and 75 healthy controls. Plasma levels of LPA and cancer antigen 125 (CA‐125) were measured in all study subjects. The diagnostic values of LPA and CA‐125 plasma levels were evaluated and an updated meta‐analysis was performed to examine the association between LPA plasma levels and OC progression. Statistical analyses were performed with spss 18.0 and R 3.1.0 software.

Results

In our case–control study, OC patients showed significantly higher plasma LPA levels compared to patients with benign tumors and healthy controls (all P < 0.05). Plasma LPA levels exhibited higher diagnostic sensitivity (P = 0.008) and specificity (P = 0.042) in detecting OC, compared to an established marker, CA‐125. Notably, the sensitivity for early stage OC was significantly higher for plasma LPA levels in comparison to CA‐125 (P < 0.05). Consistent with this, the area under the receiver–operator curve was greater for LPA (0.899) in comparison to that for CA‐125 (0.751). Further, meta‐analysis showed that plasma LPA levels were significantly higher in OC patients compared to patients with benign tumors or healthy controls (all P < 0.05).

Conclusion

Plasma LPA levels are elevated in OC patients and correlate with disease progression. Further, LPA shows higher sensitivity and specificity in OC diagnosis, compared to CA‐125, especially in early stage OC.
Percutaneous absorption of chemicals: developing an understanding for the treatment of disease in frogs
Authors: Llewelyn V. K. , Berger L. , Glass B. D.
Published: October 2015

The permeable nature of frog skin presents an alternative route for the delivery of therapeutic chemicals to treat disease in frogs. However, although therapeutic chemicals are often topically applied to the skin of frogs, their pharmacokinetics have rarely been reported. To provide evidence to guide both candidate drug and formulation selection, we highlight factors expected to influence percutaneous absorption through frog skin, including the anatomy and physiology of the skin and the physicochemical properties of applied therapeutic chemicals. Importantly, we also highlight the effects of the formulation on percutaneous absorption, especially the inclusion of potential penetration enhancers as excipients. Finally, we collate empirical data on the topical application of various therapeutic chemicals in postmetamorphic frogs and show that, in contrast to mammalian species, even large chemicals (i.e. >500 Da) and those with a wide range of logPvalues (−4 through +6) are likely to be absorbed percutaneously. Topical application in frogs thus promises a convenient and effective method for delivering systemic treatments of a diverse range of chemicals; however, further experimental quantification is required to ensure optimal outcomes.
Effect of socioeconomic status on hepatocellular carcinoma incidence and stage at diagnosis, a population‐based cohort study
Authors: Anyiwe Kika , Qiao Yao , De Prithwish , Yoshida Eric M. , Earle Craig C. , Thein Hla‐Hla
Published: October 2015

Background & Aims

Hepatocellular carcinoma (HCC) incidence is increasing worldwide and cirrhosis is the most important risk factor predominantly caused by chronic viral hepatitis infection. We studied the impact of socioeconomic status (SES) on HCC incidence and stage at diagnosis among viral hepatitis cases.

Methods

A population‐based retrospective cohort study was conducted through the Ontario Cancer Registry linked data. Incidence rates were calculated using person‐time methodology. Association between SES (income quintile) and HCC incidence was assessed using proportional‐hazards regression. The impact of SES on HCC stage was investigated using logistic regression.

Results

Among 11 350 individuals diagnosed with viral hepatitis between 1991 and 2010, a crude HCC incidence rate of 21.4 cases per 1000 person‐years was observed. Adjusting for age, gender, urban/rural residence and year of viral hepatitis diagnosis, a significant association was found between SES and HCC incidence, with an increased risk among individuals in the lowest three income quintiles (incidence rate ratio, IRR = 1.235; 95% CI: 1.074–1.420; IRR = 1.183; 95% CI: 1.026–1.364; IRR = 1.158; 95% CI: 1.000–1.340 respectively). No significant association between SES and HCC incidence was found after additionally adjusting for risk factors associated with HCC. However, HCC risk factors such as cirrhosis and HIV are associated with SES. Furthermore, no association was found between SES and HCC stage.

Conclusions

The association between SES and HCC incidence is likely because of differences in risk factors across income quintiles. Investigating how SES affects HCC incidence facilitates an understanding of which populations are at elevated risk for HCC.
Comparative chemical screening and genetic analysis reveal tentoxin as a new virulence factor in Cochliobolus miyabeanus, the causal agent of brown spot disease on rice
Authors: De Bruyne Lieselotte , Van Poucke Christof , Di Mavungu Diana Jose , Zainudin Nur Ain Izzati Mohd , Vanhaecke Lynn , De Vleesschauwer David , Turgeon B. Gillian , De Saeger Sarah , Höfte Monica
Published: October 2015

Brown spot disease, caused by Cochliobolus miyabeanus, is currently considered to be one of the most important yield reducers of rice (Oryza sativa L.). Despite its agricultural importance, little is known about the virulence mechanisms deployed by the fungus. Therefore, we set out to identify novel virulence factors with a role in disease development. This article reports, for the first time, the production of tentoxin by C. miyabeanus as a virulence factor during brown spot disease and the identification of the non‐ribosomal protein synthetase (NRPS) CmNps3, responsible for tentoxin biosynthesis. We compared the chemical compounds produced by C. miyabeanus strains differing in virulence ability using ultra‐high‐performance liquid chromatography (UHPLC) coupled to high‐resolution Orbitrap mass spectrometry (HRMS). The production of tentoxin by a highly virulent strain was revealed by principal component analysis of the detected ions and confirmed by UHPLC coupled to tandem‐quadrupole mass spectrometry (MS/MS). The corresponding NRPS was identified by in silico genome analysis and confirmed by gene deletion. Infection tests with wild‐type and Cmnps3 mutants showed that tentoxin acts as a virulence factor and is correlated with chlorosis development during the second phase of infection. Although rice has previously been classified as a tentoxin‐insensitive plant species, our data demonstrate that tentoxin production by C. miyabeanus affects symptom development.
Relationship between anaemia management at haemodialysis initiation and patient prognosis
Authors: Kataoka Hiroshi , Tsuchiya Ken , Naganuma Toshiaki , Okazaki Masayuki , Komatsu Mizuki , Kimura Tomonori , Shiohira Shunji , Kawaguchi Hiroshi , Nitta Kosaku
Published: October 2015

Aim

It has been suggested that anaemia management during a transition period to haemodialysis could influence prognosis. In this paper, we have conducted a retrospective investigation on how Hb levels at haemodialysis initiation in patients with chronic kidney disease (CKD) influence the risk of cerebral infarction and cardiovascular events.

Methods

Seventy‐two patients who underwent initial haemodialysis between May 2012 and April 2014 were designated as subjects of the study and the patients were divided into a cohort with Hb levels ≥8 g/dL and a cohort with <8 g/dL at haemodialysis initiation. The occurrence of cardiovascular events was analyzed using the Kaplan−Meier method and Cox proportional hazards model.

Results

The cohort with <8 g/dL Hb levels at haemodialysis initiation demonstrated a tendency toward low dosage of ESA or iron preparation in the pre‐haemodialysis (maintenance) phase. Significant incidence of cardiovascular (log rank, P = 0.002) and cerebrovascular (log rank, P = 0.02) events was observed. The results of multivariate analysis of the Cox proportional hazards model indicated that anaemia with <8 g/dL Hb levels at haemodialysis initiation was a significant risk factor for coronary artery (hazard ratio = 12.85, P = 0.003) and cerebrovascular (hazard ratio = 5.11, P = 0.04) diseases post‐haemodialysis.

Conclusion

The results of this investigation indicate the possible involvement of low Hb levels at haemodialysis initiation as a factor in cardio‐ and cerebrovascular events. There, our results suggested that the administration of adequate dosage of iron preparations and ESA in the pre‐haemodialysis period could help prevent cardio‐ and cerebrovascular events.
EMPLOYEE TURNOVER IN HYBRID ORGANIZATIONS: THE ROLE OF PUBLIC SECTOR SOCIALIZATION AND ORGANIZATIONAL PRIVATENESS
Authors: KRØTEL SARAH M.L. , VILLADSEN ANDERS R.
Published: October 2015

Public sector reforms are increasingly blurring the boundaries between the public and private sectors, making way for hybrid organizations existing between the two sectors. While research has begun to explore organizational hybridity and how it affects employee identities and outcomes, knowledge about employee behaviour in hybrid organizations is scarce. Public–private hybrid organizations face the challenge of balancing some degree of privateness with traditional public sector practices and values. In this article we focus on public sector companies as an increasingly prevalent type of hybrid organization, and how employee turnover is affected by the degree of organizational privateness. We suggest that highly socialized public sector employees are more likely to leave when their organization exhibits higher levels of privateness. In an empirical study of all employees in public sector companies in Denmark we find support for this theory. The article contributes new knowledge about employee turnover dynamics and how the balance of opposing demands in hybrid organizations has implications for employee behaviour.
OPINION: Primary prevention of allergy – Will it soon become a reality?
Authors: Van Bever Hugo P. , Nagarajan Sowmya , Shek Lynette P. , Lee Bee‐Wah
Published: October 2015

It is generally accepted that allergic diseases are not curable and not preventable, but mainly controllable using pharmacotherapy (i.e. symptomatic medication). Recent research, however, demonstrated that a number of specific interventions can lead to (partial) primary prevention of allergy, especially of atopic dermatitis (AD) and food allergy (FA). Three types of primary prevention strategies have been successfully studied: early administration of bacterial products (most studies are on probiotics), early moisturizing in infants at risk for AD and early exposure to allergenic foods (peanut and egg). Results of these studies indicate that the stage might have been set. Surely, much more research needs to be carried out before advice can be given in clinical practice. This opinion article discusses the three types of beneficial interventions and gives ideas for future research, which might show the way for better strategies in primary prevention of allergic diseases.
Evaluation of lung function on impulse oscillometry in preschool children born late preterm
Authors: Er Ilkay , Gunlemez Ayla , Uyan Zeynep Seda , Aydogan Metin , Oruc Meral , Isik Olcay , Arisoy Ayse Engin , Turker Gulcan , Baydemir Canan , Gokalp Ayse Sevim
Published: October 2015

Background

There is a paucity of data on lung physiology in late‐preterm children, who may be exposed to a risk of decline in lung function during childhood. In this study, we evaluated lung function in preschool children born late preterm using impulse oscillometry (IOS), and compared the results with those obtained in healthy term‐born children.

Methods

Children between 3 and 7 years of age who were born late preterm and who were being followed up at the outpatient clinic were included as the late‐preterm group. Age‐matched healthy term‐born children served as controls. A total of 90 late‐preterm and 75 healthy children were included in the study. At 5–20 Hz, resistance (R5–R20), reactance (X5–X20), impedans (Z5) and resonant frequency were measured on IOS.

Results

Mean IOS R5 and R10 were significantly higher in the late‐preterm group than in the control group (P < 0.05). Mean R5, R10 and Z5 were statistically higher in late‐preterm children who had been hospitalized for pulmonary infection compared with the control group (P < 0.05). Mean R5, R10, R15, R20 and Z5 were significantly higher, and mean X10 and X15 significantly lower in late‐preterm children with passive smoking compared with late‐preterm children without passive smoking and controls (P < 0.05).

Conclusion

Children born late preterm had signs of peripheral airway obstruction on IOS‐based comparison with healthy term‐born controls. Besides the inherent disadvantages of premature birth, hospitalization for pulmonary infection and passive smoking also seemed to adversely affect lung function in children born late preterm.
Successful treatment of severe acute antibody‐mediated rejection of renal allografts with bortezomib – a report of two pediatric cases
Authors: Roberti Isabel , Vyas Shefali
Published: October 2015

aAMR in renal allografts is uncommon and remains a challenge as it is often refractory to treatment modalities. Aggressive therapy is essential to reverse the rejection as it results in renal allograft loss in approximately 27–40% of cases. There are anecdotal case reports of use of bortezomib, a proteasome inhibitor in the treatment of resistant AMR cases in solid organ transplant recipients; however, the experience is limited. We herein report successful reversal of resistant aAMR in two pediatric patients with bortezomib. Patients were initially treated with IV methylprednisolone pulse therapy with IVIG and PP three times weekly for a total of 10 treatments. After the standard therapy used at our institution persistence of DSA associated with graft dysfunction prompted the use of bortezomib to further treat the rejection. We did not have any neurologic side effects, but one patient did experience significant infections after bortezomib infusions requiring prolonged antimicrobial therapy. The long‐term outcome of both children was excellent with preservation of normal renal function and persistent reduction in DSA titers.
A Short‐Term, Prospective Test of the Interpersonal–Psychological Theory of Suicidal Ideation in an Adolescent Clinical Sample
Authors: Miller Adam Bryant , Esposito‐Smythers Christianne , Leichtweis Richard N.
Published: October 2015

The present prospective study tested a portion of the interpersonal–psychological theory of suicide (IPTS) in an adolescent clinical sample. Participants were 143 adolescents consecutively admitted to a partial hospitalization program who completed assessments at intake and discharge from the program. Results partially supported the IPTS and suggest that (1) perceived burdensomeness may be an important socially based cognition for understanding concurrent risk for suicidal ideation (SI); (2) thwarted belongingness affects depression symptom severity over time, which indirectly predicts SI over a short follow‐up time frame; and (3) the IPTS constructs may function differently in a high‐risk clinical adolescent sample, compared to adults, although findings are preliminary.
Optimization of the measurement procedure during multiphoton tomography of human skin in vivo
Authors: Springer S. , Zieger M. , Koenig K. , Kaatz M. , Lademann J. , Darvin M. E.
Published: October 2015

Background

The in vivo multiphoton tomography has evolved into a useful tool for the non‐invasive investigation of morphological and biophysical characteristics of human skin. Until now, changes of skin have been evaluated mainly by clinical and histological techniques. The current study addresses the effects of a changed acquisition time for single scans in a Z‐stack on the directly related qualitative and quantitative interpretability of the data.

Methods

A test area of the skin was used for scanning 12 Z‐stacks of 10 volunteers aged between 25 and 34 years. The stacks were taken up to a depth of 220 μm at increments of 10 μm at four different times, 1, 3, 7, 13 s, per scan. Subsequently, the second harmonic generation (SHG)‐to‐autofluorescence aging index of dermis (SAAID) was evaluated at three different measuring depths, i.e. at the maximum of SHG as well as at depths of 60 and 150 μm.

Results

The evaluation did not reveal any significant differences in the SAAID behavior between the Z‐stacks of each test area scanned at different acquisition times. However, the acquisition time of 1 s/frame increases the measurement stability without influencing the SAAID behavior. The resolution of subcellular structures decreases significantly at scan times ≤3 s, whereas the acquisition time from 7 to 13 s warrants a high image quality.

Conclusion

The study has shown that there are no significant differences between the scan speeds per scan in a Z‐stack and the resulting SAAID. Acquisition times of 7 s are suitable for the morphological evaluation whereas a further extension to 13 s does not result in any benefits. A scan time per image of 1 s is sufficient for the quantitative evaluation of SAAID thus substantially reducing the possible influence of movement artifacts.
Epidemiology and risk factors of multidrug‐resistant bacteria in respiratory samples after lung transplantation
Authors: Tebano G. , Geneve C. , Tanaka S. , Grall N. , Atchade E. , Augustin P. , Thabut G. , Castier Y. , Montravers P. , Desmard M.
Published: October 2015

Background

Multidrug‐resistant (MDR) bacteria are a growing concern worldwide. The aim of this study was to describe the epidemiology and risk factors of MDR bacteria detected in respiratory invasive samples during hospitalization in the intensive care unit (ICU) after lung transplantation (LT).

Methods

This study was based on a retrospective analysis of 176 patients hospitalized in the ICU after LT in 2006–2012. Respiratory invasive samples were performed according to a routine protocol. MDR pathogens were defined according to in vitro susceptibility tests.

Results

A total of 1176 bacteria were cultured. Susceptibility testing was performed on 1046 strains and 404 (39%) MDR were detected in 90 (51%) patients. Pseudomonas aeruginosa, coagulase‐negative staphylococci, and Enterobacteriaceae (mainly Enterobacter species) were the most common MDR pathogens. On multivariate analysis, an ICU stay >14 days, presence of a tracheostomy, and previous exposure to broad‐spectrum antibiotics were associated with MDR acquisition (odds ratio [OR] 3.7; 95% confidence interval [1.69–8.12]; OR 3.28 [1.05–10.28]; and OR 2.25 [1.17–4.34], respectively). We consistently observed an increasing emergence of resistance to several antibiotics, from week 1 to week 4 of ICU hospitalization: for ticarcillin, piperacillin–tazobactam, ceftazidime, imipenem/cilastatin, amikacin, and ciprofloxacin in P. aeruginosa; and for piperacillin–tazobactam, cefepime, and amikacin in Enterobacteriaceae.

Conclusion

A large proportion of MDR bacteria are detected on respiratory invasive samples in LT patients, and the risk of their emergence is mainly determined by the previous exposure to broad‐spectrum antibiotics and the length of ICU stay. Adequate treatment requires broad‐spectrum empiric antibiotic therapy.
The impact on blood donor screening for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus using plasma from frozen‐thawed plasma preparation tubes
Authors: Allison Kirsty M. , Faddy Helen M. , Margaritis Angelo , Ismay Susan , Marks Denese C.
Published: October 2015

BACKGROUND

Blood services are required to maintain repositories of frozen samples for confirmation of results and/or retrospective testing. The Australian Red Cross Blood Service archives donor samples in plasma preparation tubes (PPTs). This study aims to evaluate the effect of freeze‐thawing and extended frozen storage on the ability to detect human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) using blood donation screening assays in samples stored in PPTs.

STUDY DESIGN AND METHODS

Whole blood was spiked with HIV‐, HCV‐, or HBV‐reactive plasma at high and low viral loads and stored in PPTs or as plasma aliquots. All samples were frozen and stored at not more than −30°C. At 0, 3, 6, 12, 18, and 36 months, samples were tested for HIV and HCV antibodies, HBV surface antigen, and viral nucleic acid. Additional samples were thawed and refrozen either once or twice before testing to simulate up to three freeze‐thaw cycles.

RESULTS

All PPT and plasma aliquots retained appropriate viral reactivity, including those with multiple freeze‐thaw cycles, on both nucleic acid testing and serology platforms.

CONCLUSION

Frozen storage of biologicals in PPTs, as opposed to plasma aliquots, does not affect the ability to detect HIV, HCV, and HBV using viral nucleic acid or serology donation screening systems for up to 36 months. Freezing and thawing PPT samples did not impact the ability to detect these viruses. Our study demonstrates that PPTs appear to be an appropriate receptacle for frozen plasma sample archiving for up to 3 years.
Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring
Authors: Walton Sarah L. , Singh Reetu R. , Tan Tiffany , Paravicini Tamara M. , Moritz Karen M.
Published: October 2015

Key points

Maternal hypoxia is a common perturbation that leads to growth restriction and may program vascular dysfunction in adult offspring.

An adverse prenatal environment may render offspring vulnerable to increased cardiovascular risk when challenged with a ‘second hit’, such as a high salt diet.

We investigated whether maternal hypoxia impaired vascular function, structure and mechanics in mouse offspring, and also whether this was exacerbated by excess dietary salt intake in postnatal life.

Maternal hypoxia predisposed adult male and female offspring to endothelial dysfunction.

The combination of prenatal hypoxia and high dietary salt intake caused significant stiffening of mesenteric arteries, and also altered structural characteristics of the aorta consistent with vascular stiffening.

The results of the present study suggest that prenatal hypoxia combined with a high salt diet in postnatal life can contribute to vascular dysfunction.

Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch‐up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress–strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes.