bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the effect of oral administration of Echinacea hydroethanolic extract on the immune system in dog
Authors: Torkan S. , Khamesipour F. , Katsande S.
Published: April 2015

This study was designed to evaluate the effects of oral administration of Echinacea hydroethanolic extract on the dog's immune system.

The study was performed on 14 dogs that were referred to the veterinary clinic. These dogs were randomly allocated to two equal treatment groups. The first group received 1 ml of 5% Echinacea hydroethanolic extract two times a day for 2 months, and the second group received a placebo (water). To do haematology and immunology tests, the dogs were bled on days 0, 30 and 60. Blood tests, including packed cell volume (PCV), haemoglobin (Hb), red blood cell count (RBC), white blood cell count (WBC), counting neutrophils (Nut), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), basophils (Baso) and B cell, were performed. Furthermore, safety factor IgM and per cent of phagocytosis and phagocyte were measured from the blood sample.

The results showed that in the group which received Echinacea PCV, Hb, RBC count, WBC count, Lym, Nut, the per cent of phagocytosis and IgM significantly increased (P < 0.05). Moreover, positive effects of Echinacea plant on the immune system were observed. There was a significant change in HTC, RBC, Hb over time in the group that received Echinacea and the per cent of phagocytosis and IgM (P < 0.05).

The study establishes that these extracts might have appreciable immunostimulatory activity. However, further studies are required to confirm these findings.
New ways to provide community aged care services
Authors: Taylor Chris , Donoghue Jed
Published: April 2015

This paper will focus on the provision of community aged care services via ‘direct payments’ and ‘social enterprise’. These are two solutions that were not fully considered by the Productivity Commission as a way to make the provision of community aged care more sustainable in Australia. The empowerment component of social enterprise activities and ‘direct payments’ have the potential to generate improvements in the community aged care system.
Activation of KIT modulates the function of tumor necrosis factor‐related apoptosis‐inducing ligand receptor (TRAIL‐R) in mast cells
Authors: Förster A. , Grotha S. P. , Seeger J. M. , Rabenhorst A. , Gehring M. , Raap U. , Létard S. , Dubreuil P. , Kashkar H. , Walczak H. , Roers A. , Hartmann K.
Published: April 2015

Background

Mastocytosis is characterized by the accumulation of mast cells (MCs) associated with activating mutations of KIT. Tumor necrosis factor‐related apoptosis‐inducing ligand receptors (TRAIL‐Rs) are preferentially expressed on neoplastic cells and induce the extrinsic apoptotic pathway. Recent studies reported on the expression of TRAIL‐Rs and TRAIL‐induced apoptosis in cultured human MCs, which depend on stem cell factor (SCF)‐induced or constitutive KIT activation.

Material and methods

We sought to further define the impact of TRAIL‐Rs on MCs in vivo and in vitro. Using Cre/loxP recombination, we generated mice with MC‐specific and ubiquitous knockout of TRAIL‐R. In these mice, anaphylaxis and numbers of MCs were investigated. We also explored the expression and function of TRAIL‐Rs in cultured murine and human MCs upon activation of KIT. By conducting immunofluorescence staining, we analyzed the expression of TRAIL‐Rs in MCs infiltrating the bone marrow of patients with mastocytosis.

Results

MC‐specific deletion of TRAIL‐R was associated with a slight, but significant increase in anaphylaxis. Numbers of MCs in MC‐specific knockouts of TRAIL‐R were comparable to controls. Whereas cultured IL‐3‐dependent murine MCs from wild‐type mice were resistant to TRAIL‐induced apoptosis, SCF‐stimulated MCs underwent apoptosis in response to TRAIL. Interestingly, activating KIT mutations also promoted sensitivity to TRAIL‐mediated apoptosis in human MCs. In line with these findings, MCs infiltrating the bone marrow of patients with mastocytosis expressed TRAIL‐R1.

Conclusions

Activation of KIT regulates the function of TRAIL‐Rs in MCs. TRAIL‐R1 may represent an attractive diagnostic and therapeutic target in diseases associated with KIT mutations, such as mastocytosis.
Notch signaling mediates granulocyte‐macrophage colony‐stimulating factor priming‐induced transendothelial migration of human eosinophils
Authors: Liu L.Y. , Wang H. , Xenakis J. J. , Spencer L. A.
Published: April 2015

Background

Priming with cytokines such as granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM‐CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell‐intrinsic cues. This study investigates the hypothesis that the priming‐induced enhanced migration of human eosinophils requires the Notch signaling pathway.

Methods

Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM‐CSF‐primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo.

Results

Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM‐CSF priming impaired priming‐enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK‐MAPK activation was required for GM‐CSF priming‐induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor.

Conclusions

These data identify Notch signaling as an intrinsic pathway central to GM‐CSF priming‐induced eosinophil tissue migration.
Using the Strengths and Difficulties Questionnaire (SDQ) to Predict Emotional and Behavioral Difficulties on Positive and Negative Affect Among Adolescents in Disadvantaged Communities
Authors: Abdul Kadir Nor Ba'yah , Mustapha Zaidah , Abdul Mutalib Mimi Hanida , Yakub Nur Asyikin
Published: April 2015

The Strengths and Difficulties Questionnaire (SDQ) was used to predict the positive and negative affects of emotional and behavioral difficulties among adolescent boys and girls aged between 14 and 21 years living in disadvantaged communities. A total of 316 adolescents—181 boys and 135 girls—living in the Seri Pantai and Pantai Ria Public Housing Projects in Kuala Lumpur were invited to complete the questionnaire. The results showed that conduct and peer problems were the most prevalent emotional and behavioral difficulties experienced by these adolescents. As expected, the emotional symptoms were more common among the girls than the boys. A further analysis showed that emotional symptoms, peer problems, and low prosocial behavior were predictors of the negative affect of emotional and behavioral difficulties while negative emotional symptoms and high hyperactivity were predictors of a positive affect. The findings suggested that three subscales of SDQ are required to produce a negative affect, and two subscales of SDQ for a positive affect.
Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways
Authors: Pipicz Márton , Varga Zoltán V , Kupai Krisztina , Gáspár Renáta , Kocsis Gabriella F , Csonka Csaba , Csont Tamás
Published: April 2015

Background and Purpose

Rapid ventricular pacing (RVP) applied before an index ischaemia has anti‐ischaemic effects. Here, we investigated whether RVP applied after index ischaemia attenuates reperfusion injury and whether peroxynitrite, reperfusion injury salvage kinase (RISK) and survival activating factor enhancement (SAFE) pathways as well as haem oxygenase 1 (HO1) are involved in the mechanism of RVP‐induced postconditioning.

Experimental Approach

Langendorff perfused rat hearts were subjected to 30 min regional ischaemia and 120 min reperfusion with or without ischaemic postconditioning (6 × 10/10 s reperfusion/ischaemia; IPost) or RVP (6 × 10/10 s non‐pacing/rapid pacing at 600 bpm) applied at the onset of reperfusion.

Key Results

Meta‐analysis of our previous studies revealed an association between longer reperfusion‐induced ventricular tachycardia/fibrillation with decreased infarct size. In the present experiments, we tested whether RVP is cardioprotective and found that both IPost and RVP significantly decreased infarct size; however, only RVP attenuated the incidence of reperfusion‐induced ventricular tachycardia. Both postconditioning methods increased the formation of cardiac 3‐nitrotyrosine and superoxide, and non‐significantly enhanced Akt phosphorylation at the beginning of reperfusion without affecting ERK1/2 and STAT3, while IPost alone induced HO1. Application of brief ischaemia/reperfusion cycles or RVP without preceding index ischaemia also facilitated peroxynitrite formation; nevertheless, only brief RVP increased STAT3 phosphorylation.

Conclusions and Implications

Short periods of RVP at the onset of reperfusion are cardioprotective and increase peroxynitrite formation similarly to IPost and thus may serve as an alternative postconditioning method. However, downstream mechanisms of the protection elicited by IPost and RVP seem to be partially different.

Linked Articles

This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma
Authors: Nakazawa Atsuko , Haga Chizuko , Ohira Miki , Okita Hajime , Kamijo Takehiko , Nakagawara Akira
Published: April 2015

The International Neuroblastoma Pathology Classification (INPC) has a prognostic impact that distinguishes two categories of neuroblastoma: favorable histology (FH) and unfavorable histology (UH). We analyzed 92 cases of neuroblastoma with the INPC evaluation and genomic grouping to investigate the correlation between the INPC and genomic signature, together with their prognostic significance. The correlation of UH tumor and partial gains and/or losses (GGP), as well as the correlation of FH tumor and whole gains and/or losses (GGW), was statistically significant. Both UH and GGP were late‐onset (median age at diagnosis was 36 and 48 months, respectively) and had poor prognosis (overall survival rate [OS], 43.1% and 42.4%, respectively). In contrast, both FH and GGW were early‐onset (median age at diagnosis, 4 and 9.5 months, respectively) and had favorable prognosis (OS, 88.6% and 87.1%, respectively). Unfavorable histology and GGP had significantly inferior OS compared to FH and GGW. Overall survival was not significantly different among the genomic groups in FH; however, it was inferior in UH with GGP. In UH with a single copy MYCN, genomic subgroups GGP2s (both 1p and 11q losses) and GGP3s (partial 11q loss but not 1p loss) indicated significantly poor prognosis compared to GGP4s (no partial 1p and 11q loss). As INPC and MYCN amplification were found to be the most powerful prognostic biological factors, they should be included with genomic grouping as treatment stratification for patients with UH and single copy of MYCN.
Novel Selective Inhibitor of Leishmania (Leishmania) amazonensis Arginase
Authors: da Silva Edson R. , Boechat Nubia , Pinheiro Luiz C. S. , Bastos Monica M. , Costa Carolina C. P. , Bartholomeu Juliana C. , da Costa Talita H.
Published: April 2015

Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and trypanothione biosynthesis. The central role of arginase in Leishmania (Leishmania) amazonensis was demonstrated by the generation of two mutants: one with an arginase lacking the glycosomal addressing signal and one in which the arginase‐coding gene was knocked out. Both of these mutants exhibited decreased infectivity. Thus, arginase seems to be a potential drug target for Leishmania treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the [1,2,4]triazolo[1,5‐a]pyrimidine system were tested against Leishmania (Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5‐a]pyrimidine scaffold containing R1 = CF3 exhibited greater activity against the arginase rather than when the substituent R1 = CH3 in the 2‐position. The novel compound 2‐(5‐methyl‐2‐(trifluoromethyl)‐[1,2,4]triazolo[1,5‐a]pyrimidin‐7‐yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non‐competitive mechanism, with the Ki and IC50 values for arginase inhibition estimated to be 17 ± 1 μm and 16.5 ± 0.5 μm, respectively. These results can guide the development of new drugs against leishmaniasis based on [1,2,4]triazolo[1,5‐a]pyrimidine derivatives targeting the arginase enzyme.
Prediction of Human Clearance Based on Animal Data and Molecular Properties
Authors: Huang Wenkang , Geng Lv , Deng Rong , Lu Shaoyong , Ma Guangli , Yu Jianxiu , Zhang Jian , Liu Wei , Hou Tingjun , Lu Xuefeng
Published: April 2015

Human clearance is often predicted prior to clinical study from in vivo preclinical data by virtue of interspecies allometric scaling methods. The aims of this study were to determine the important molecular descriptors for the extrapolation of animal data to human clearance and further to build a model to predict human clearance by combination of animal data and the selected molecular descriptors. These important molecular descriptors selected by genetic algorithm (GA) were from five classes: quantum mechanical, shadow indices, E‐state keys, molecular properties, and molecular property counts. Although the data set contained many outliers determined by the conventional Mahmood method, the variation of most outliers was reduced significantly by our final support vector machine (SVM) model. The values of cross‐validated correlation coefficient and root‐mean‐squared error (RMSE) for leave‐one‐out cross‐validation (LOOCV) of the final SVM model were 0.783 and 0.305, respectively. Meanwhile, the reliability and consistency of the final model were also validated by an external test set. In conclusion, the SVM model based on the molecular descriptors selected by GA and animal data achieved better prediction performance than the Mahmood method. This approach can be applied as an improved interspecies allometric scaling method in drug research and development.
Neuronal activity‐dependent regulation of retinal blood flow
Authors: Noonan Jonathan E , Lamoureux Ecosse L , Sarossy Marc
Published: April 2015

Blood flow in the retina is intrinsically regulated to meet the metabolic demands of its constituent cells. Flickering light or stationary contrast reversals induce an increase in blood flow within seconds of the stimulus onset. This phenomenon is thought to compensate for an increase in ganglion cell activity and energy consumption. Ganglion cell activity is in turn dependent on signals from photoreceptors, bipolar cells, horizontal cells and amacrine cells. The physiological properties of these neurons determine how each type is affected by a particular light characteristic. Neuronal activity then triggers the release of signalling molecules that dilate local blood vessels and increase blood flow. Nitric oxide has been implicated as an important mediator, but metabolites of arachidonic acid may also be involved. Detailed elucidation of these mechanisms, together with advances in imaging technology, may facilitate the use of neurovascular tests to improve the detection of retinal damage in pathological conditions.
Pulmonary acantholytic squamous cell carcinoma with focal signet ring cell morphology mimicking malignant mesothelioma on fine needle aspiration cytology: a case report
Authors: Choi S.‐E. , Park H. S.
Published: April 2015

Features such as optically dense cytoplasm, endo‐ectoplasmic demarcation, occasional intracytoplasmic vacuoles and round nuclei may make the identification of this rare variant of squamous cell carcinoma difficult to identify and to distinguish from epithelioid mesothelioma.
Weighing privacy against effective epidemiology
Authors: Hutton Jane L
Published: April 2015

This commentary is on the original article by Lehtonen et al. on pages 645–651 of this issue.
Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16‐week, randomized, placebo‐controlled trial
Authors: Ross S. , Thamer C. , Cescutti J. , Meinicke T. , Woerle H. J. , Broedl U. C.
Published: April 2015

Patients with type 2 diabetes mellitus (T2DM) with a glycated haemoglobin (HbA1c) level ≥7 and ≤10% were randomized to receive empagliflozin 12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220), or placebo (n = 107) as add‐on to stable‐dose metformin immediate release (IR) twice daily for 16 weeks. The primary endpoint was change from baseline in HbA1c at week 16. At week 16, change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa. The adjusted mean (95% confidence interval) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11% (−0.26, 0.03), and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02% (−0.16, 0.13). All empagliflozin regimens were well tolerated; thus, when used as add‐on to metformin IR in patients with T2DM, the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent.
Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats
Authors: Lundh M. , Galbo T. , Poulsen S. S. , Mandrup‐Poulsen T.
Published: April 2015

Failure of pancreatic β cells to compensate for insulin resistance is a prerequisite for the development of type 2 diabetes. Sustained elevated circulating levels of free fatty acids and glucose contribute to β‐cell failure. Selective inhibition of histone deacetylase (HDAC)‐3 protects pancreatic β cells against inflammatory and metabolic insults in vitro. In the present study, we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce hyperglycaemia and increase insulin secretion in a rat model of type 2 diabetes. At diabetes onset, an ambulatory hyperglycaemic clamp was performed. HDAC3 inhibition improved hyperglycaemia over the study period without affecting weight gain. At the end of the hyperglycaemic clamp, circulating insulin levels were significantly higher in BRD3308‐treated rats. Pancreatic insulin staining and contents were also significantly higher. These findings highlight HDAC3 as a key therapeutic target for β‐cell protection in type 2 diabetes.
Treatment escalation options for patients with type 2 diabetes after failure of exenatide twice daily or glimepiride added to metformin: results from the prospective European Exenatide (EUREXA) study
Authors: Schernthaner G. , Rosas‐Guzmán J. , Dotta F. , Guerci B. , Simó R. , Festa A. , Kiljański J. , Zhou M. , Gallwitz B.
Published: April 2015

Aims

To evaluate third‐line thiazolidinedione (TZD) or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily, and third‐line exenatide twice daily in patients inadequately controlled on metformin + glimepiride.

Methods

In this randomized, open‐label, multicentre trial, 144 patients with type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two consecutive visits 3 months apart, after 6 months' treatment] on metformin + exenatide twice daily were re‐randomized to add‐on TZD or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add‐on exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids, hypoglycaemia and vital signs were evaluated.

Results

The median duration of triple therapy was ∼2 years. In patients inadequately controlled on metformin + exenatide twice daily, add‐on TZD decreased HbA1c levels significantly better than add‐on glimepiride: 130‐week difference 0.48% [95% confidence interval (CI) 0.19–0.77] or 5.2 mmol/mol (95% CI 2.1–8.4; p = 0.001), but with significantly increased BMI and systolic blood pressure. The ratio of documented symptomatic (blood glucose ≤70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add‐on glimepiride to add‐on TZD was 8.48 (p < 0.0001). Add‐on exenatide twice daily after metformin + glimepiride significantly reduced HbA1c levels: mean [standard deviation (s.d.)] change from baseline −0.35 (0.89)% [−3.8 (9.7) mmol/mol] and BMI: mean (s.d.) change from baseline −0.82 (1.9) kg/m2 at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycaemia from metformin + glimepiride (ratio 1.49).

Conclusions

TZD, but not glimepiride, was an effective and well tolerated third‐line therapy in patients without glycaemic control after long‐term therapy with metformin + exenatide twice daily. Exenatide twice daily was an effective and well tolerated third‐line therapy in patients inadequately controlled on metformin + glimepiride.
Modulation of platelet and monocyte function by the chemokine fractalkine (CX3CL1) in cardiovascular disease
Authors: Flierl Ulrike , Bauersachs Johann , Schäfer Andreas
Published: April 2015

Background

The chemokine fractalkine, CX3CL1, bears unique features within the chemokine family: it exists in a membrane bound form acting as an adhesion molecule and surface receptor; however, when cleaved by ADAM 10, it functions as a soluble chemokine. Fractalkine and its chemokine receptor CX3CR1 are known to have multiple roles in diverse human diseases, for example inflammatory diseases, rheumatoid arthritis, renal diseases and atherosclerosis.

Materials and methods

This review is based on the material obtained via PubMed up to November 2014. The key search terms used were ‘fractalkine’, ‘CX3CL1’, ‘CX3CR1’, ‘cardiovascular disease’, ‘platelets’, ‘monocytes’ and ‘platelet–monocyte complexes’.

Results

Atherosclerosis is recognized as a highly inflammatory disease, and it has become increasingly evident that the immune system plays an important role in atherogenesis and atheroprogression. Two blood cell populations are crucially involved in the early development of atherosclerotic lesions: monocytes and platelets. They are detected at vascular sites of endothelial dysfunction and are involved in inflammatory immune responses. These cells directly interact with each other, forming platelet–monocyte complexes that are increased in cardiovascular diseases. During the development of atherosclerosis, fractalkine mediates leukocyte recruitment to the inflamed endothelium, which promotes early formation of lesions. This process only effectively works in the presence of activated platelets. It has been suggested that fractalkine and its receptor contribute to platelet–monocyte aggregate formation underlining the two important impacts of this chemokine for platelets as well as monocytes.

Conclusion

Interesting data hint at a role of fractalkine for platelet activation, adhesion and subsequent monocyte recruitment to activated endothelial cells in cardiovascular diseases. However, the exact mechanisms remain to become unravelled.
Proteomics beyond trypsin
Authors: Tsiatsiani Liana , Heck Albert J. R.
Published: April 2015

Peptide‐centered shotgun analysis of proteins has been the core technology in mass spectrometry based proteomics and has enabled numerous biological discoveries, such as the large‐scale charting of protein–protein interaction networks, the quantitative analysis of protein post‐translational modifications and even the first drafts of the human proteome. The conversion of proteins into peptides in these so‐called bottom‐up approaches is nearly uniquely done by using trypsin as a proteolytic reagent. Here, we argue that our view of the proteome still remains incomplete and this is partially due to the nearly exclusive use of trypsin. Newly emerging alternative proteases and/or multi‐protease protein digestion aim to increase proteome sequence coverage and improve the identification of post‐translational modifications, through the analysis of complementary and often longer peptides, introducing an approach termed middle‐down proteomics. Of pivotal importance for this purpose is the identification of proteases beneficial for use in proteomics. Here, we describe some of the shortcomings of the nearly exclusive use of trypsin in proteomics and review the properties of other proteomics‐appropriate proteases. We describe favorable protease traits with an emphasis on middle‐down proteomics and suggest potential sources for the discovery of new proteases. We also highlight a few examples wherein the use of other proteases than trypsin enabled the generation of more comprehensive data sets leading to previously unexplored knowledge of the proteome.
Heat waves imposed during early pod development in soybean (Glycine max) cause significant yield loss despite a rapid recovery from oxidative stress
Authors: Siebers Matthew H. , Yendrek Craig R. , Drag David , Locke Anna M. , Rios Acosta Lorena , Leakey Andrew D. B. , Ainsworth Elizabeth A. , Bernacchi Carl J. , Ort Donald R.
Published: April 2015

Heat waves already have a large impact on crops and are predicted to become more intense and more frequent in the future. In this study, heat waves were imposed on soybean using infrared heating technology in a fully open‐air field experiment. Five separate heat waves were applied to field‐grown soybean (Glycine max) in central Illinois, three in 2010 and two in 2011. Thirty years of historical weather data from Illinois were analyzed to determine the length and intensity of a regionally realistic heat wave resulting in experimental heat wave treatments during which day and night canopy temperatures were elevated 6 °C above ambient for 3 days. Heat waves were applied during early or late reproductive stages to determine whether and when heat waves had an impact on carbon metabolism and seed yield. By the third day of each heat wave, net photosynthesis (A), specific leaf weight (SLW), and leaf total nonstructural carbohydrate concentration (TNC) were decreased, while leaf oxidative stress was increased. However, A, SLW, TNC, and measures of oxidative stress were no different than the control ca. 12 h after the heat waves ended, indicating rapid physiological recovery from the high‐temperature stress. That end of season seed yield was reduced (~10%) only when heat waves were applied during early pod developmental stages indicates the yield loss had more to do with direct impacts of the heat waves on reproductive process than on photosynthesis. Soybean was unable to mitigate yield loss after heat waves given during late reproductive stages. This study shows that short high‐temperature stress events that reduce photosynthesis and increase oxidative stress resulted in significant losses to soybean production in the Midwest, U.S. The study also suggests that to mitigate heat wave‐induced yield loss, soybean needs improved reproductive and photosynthetic tolerance to high but increasingly common temperatures.
Would protecting tropical forest fragments provide carbon and biodiversity cobenefits under REDD+?
Authors: Magnago Luiz Fernando S. , Magrach Ainhoa , Laurance William F. , Martins Sebastião V. , Meira‐Neto João Augusto A. , Simonelli Marcelo , Edwards David P.
Published: April 2015

Tropical forests store vast amounts of carbon and are the most biodiverse terrestrial habitats, yet they are being converted and degraded at alarming rates. Given global shortfalls in the budgets required to prevent carbon and biodiversity loss, we need to seek solutions that simultaneously address both issues. Of particular interest are carbon‐based payments under the Reducing Emissions from Deforestation and Forest Degradation (REDD+) mechanism to also conserve biodiversity at no additional cost. One potential is for REDD+ to protect forest fragments, especially within biomes where contiguous forest cover has diminished dramatically, but we require empirical tests of the strength of any carbon and biodiversity cobenefits in such fragmented systems. Using the globally threatened Atlantic Forest landscape, we measured above‐ground carbon stocks within forest fragments spanning 13 to 23 442 ha in area and with different degrees of isolation. We related these stocks to tree community structure and to the richness and abundance of endemic and IUCN Red‐listed species. We found that increasing fragment size has a positive relationship with above‐ground carbon stock and with abundance of IUCN Red‐listed species and tree community structure. We also found negative relationships between distance from large forest block and tree community structure, endemic species richness and abundance, and IUCN Red‐listed species abundance. These resulted in positive congruence between carbon stocks and Red‐listed species, and the abundance and richness of endemic species, demonstrating vital cobenefits. As such, protecting forest fragments in hotspots of biodiversity, particularly larger fragments and those closest to sources, offers important carbon and biodiversity cobenefits. More generally, our results suggest that macroscale models of cobenefits under REDD+ have likely overlooked key benefits at small scales, indicating the necessity to apply models that include finer‐grained assessments in fragmented landscapes rather than using averaged coarse‐grained cells.
The Prevalence of Mixed Helicobacter pylori Infections in Symptomatic and Asymptomatic Subjects in Dhaka, Bangladesh
Authors: Kibria Khandoker Mohammad K. , Hossain Md Enayet , Sultana Jinath , Sarker Shafiqul A. , Bardhan Pradip Kumar , Rahman Motiur , Nahar Shamsun
Published: April 2015

Background

Helicobacter pylori is a highly genetically diverse bacterial species, which can persist in the gastric environment for decades. Recent studies have shown that single infections predominate in developed countries, whereas mixed infections are more prevalent in developing countries. Mixed infections of this bacterium may be important for adaptation to the hostile gastric environment and may facilitate dyspeptic symptoms.

Materials and Methods

To calculate the prevalence of mixed infections in symptomatic and asymptomatic subjects, 2010 H. pylori isolates collected from 83 symptomatic and 91 asymptomatic subjects from Dhaka, Bangladesh, were analyzed by (i) random amplified polymorphic DNA fingerprinting (RAPD) and (ii) multiplex PCR amplification for cagA and vacA virulence gene alleles.

Results

The overall prevalence of mixed H. pylori infection was 60.15% (77/128), indicating substantial co‐colonization in this population. We additionally found that symptomatic subjects (53%) had a significantly higher rate of mixed infection than asymptomatic individuals (36.3%) (p = .016) and that the prevalence of the cagA and vacA and vacA m1/s1 and vacA m2/s1 alleles were higher in subjects with mixed infection.

Conclusion

Our findings suggest that an increased diversity of the H. pylori strains in the gastric environment may contribute to the development of disease symptoms.
Primary central nervous system diffuse large B‐cell lymphoma has poorer immune cell infiltration and prognosis than its peripheral counterpart
Authors: Chang Chen , Lin Ching‐Hung , Cheng Ann‐Lii , Medeiros L Jeffrey , Chang Kung‐Chao
Published: April 2015

Aims

Primary central nervous system (CNS) diffuse large B‐cell lymphoma (PCNSL) is an ominous disease with a poor prognosis. The brain is an immune‐privileged sanctuary, and this may contribute to an ineffective host immune response and thus a poorer outcome. The aim of this study was therefore to study the difference in the immune composition inPCNSLand non‐CNSdiffuse large B‐cell lymphoma (DLBCL), and the role of the immune response inPCNSLprognosis.

Methods and results

Thirty‐two biopsy specimens ofPCNSLand 30 specimens of low‐stage non‐CNS DLBCLfrom immunocompetent patients formed the study group. The density and distribution of immune cells, including dendritic cells (dendritic cell‐specific lysosomal‐associated membrane protein‐positive and S100‐positive), effector/memory T cells (CD45RO‐positive), and cytotoxic T cells (granzyme B‐positive), and the expression ofHLA‐DRby lymphoma cells, were evaluated immunohistochemically.PCNSLpatients showed poorer overall survival (P = 0.032). On comparison of thePCNSLandDLBCLbiopsy specimens, thePCNSLcells showed lessHLA‐DRexpression (P = 0.003), and there were fewer S100‐positive cells (P < 0.01), and effector T cells (P = 0.026) infiltratingPCNSLthan infiltratingDLBCL. ForPCNSLpatients, fewer cytotoxic T cells in the background constituted a poor prognostic factor (P = 0.004). Intratumoral S100‐positive cell infiltration was positively correlated with T‐cell infiltration, and a T‐cell rimming pattern.

Conclusions

InPCNSL, the baseline antitumour immune response is less as compared with non‐CNS DLBCL, and this response may play a role in the poorer prognosis. Adjuvant dendritic cell and T‐cell immunotherapy may further boost treatment responses inPCNSLpatients.
International travel in the immunocompromised patient: a cross‐sectional survey of travel advice in 254 consecutive patients
Authors: Bialy C. , Horne K. , Dendle C. , Kanellis J. , Littlejohn G. , Ratnam I. , Woolley I.
Published: April 2015

Aims

Our primary aim was to determine the rate of overseas travel in immunocompromised individuals attending appropriate clinics at an Australian tertiary care hospital. We also aimed to characterise health‐seeking behaviour prior to travel and investigated sources of pre‐travel advice, compared travel patterns and activities between three specific immunosuppressed groups, and examined pre‐immunosuppression patient serology.

Methods

We implemented a cross‐sectional survey of patients between February and August 2012. This survey was implemented among three outpatient populations at Monash Medical Centre, an Australian tertiary care hospital.

Results

We recruited 254 immunosuppressed adults from three patient populations: human immunodeficiency virus‐positive individuals, renal transplant patients and rheumatology patients requiring immunosuppressive therapy. No clinical intervention was performed. In the 10 years preceding the survey, 153 (60.2%) participants reported international travel. Of these, 105 (68.6%) were immunosuppressed at the time of travel. These patients were 47.6% male and 60% Australian born. Forty per cent were visiting friends and relatives as part of their travel. Fifty‐four per cent of those immunocompromised at the time of travel were going to high‐risk destinations. Pathology files indicated that serological screening was frequently not performed prior to immunosuppression in the renal transplant and rheumatology groups.

Conclusions

Immunocompromised patients often travel to high‐risk destinations with limited or inadequate pre‐travel preparations. Doctors caring for the immunocompromised should be aware of travel risks, suitable vaccination protocols and when to refer to specialist travel clinics.
Nuclear medicine incident reporting in Australia: control charts and notification rates inform quality improvement
Authors: Larcos G. , Collins L. T. , Georgiou A. , Westbrook J. I.
Published: April 2015

Background

Australia has a statutory incident reporting system for radiopharmaceutical maladministrations, but additional research into registry data is required for the purpose of quality improvement in nuclear medicine.

Aims

We (i) used control charts to identify factors contributing to special cause variation (indicating higher than expected rates) in maladministrations and (ii) evaluated the impact of heterogeneous notification criteria and extent of underreporting among jurisdictions and individual facilities, respectively.

Methods

Anonymised summaries of Australian Radiation Incident Register reports permitted calculation of national monthly maladministration notification rates for 2007–2012 and preparation of control charts. Multivariate logistic regression assessed the association of population, insurance and regulatory characteristics with maladministration notifications in each Australian State and Territory. Maladministration notification rates from two facilities with familiarity of notification processes and commitment to radiation protection were compared with those elsewhere.

Results

Special cause variation occurred in only 3 months, but contributed to 21% of all incidents (42 of 197 patients), mainly because of ‘clusters’ of maladministrations (n = 24) arising from errors in bulk radiopharmaceutical dispensing. Maladministration notification rates varied significantly between jurisdictions (0 to 12.2 maladministrations per 100 000 procedures (P < 0.05)) and individual facilities (31.7 vs 5.8 per 100 000; χ2 = 40; 1 degree of freedom, P < 0.001).

Conclusions

Unexpected increases in maladministration notifications predominantly relate to incident ‘clusters’ affecting multiple patients. The bulk preparation of radiopharmaceuticals is a vulnerable process and merits additional safeguards. Maladministration notification rates in Australia are heterogeneous. Adopting uniform maladministration notification criteria among States and Territories and methods to overcome underreporting are warranted.
Physiological roles of miR‐155
Authors: Mashima Ryuichi
Published: April 2015

miR‐155 is involved in non‐coding microRNAs found in humans, mice and chickens of which the sequence is conserved. Historically, miR‐155 was identified as a B‐cell integration cluster (bic), which induces B‐cell leucosis in chickens, by its activation through viral promoter insertion. Subsequent studies have shown that transgenic mice expressing miR‐155 in B cells generated lymphoma, showing that miR‐155 is oncogenic. Biochemical investigation identifies many substrates of miR‐155, and one of them in B cells and macrophages is the SH2‐domain containing inositol‐5′‐phosphatase 1. A deficiency of miR‐155 in the immune system causes attenuated immune functions. Clinically, several types of malignancy including diffuse large B‐cell lymphoma have high miR‐155 expression levels.
Clinical differences between respiratory viral and bacterial mono‐ and dual pathogen detected among Singapore military servicemen with febrile respiratory illness
Authors: Ho Zheng Jie Marc , Zhao Xiahong , Cook Alex R. , Loh Jin Phang , Ng Sock Hoon , Tan Boon Huan , Lee Vernon J.
Published: April 2015

Background

Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population‐level studies describing its impact on clinical disease.

Methods

Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono‐pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation.

Results

In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non‐smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono‐infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono‐pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono‐pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono‐pathogens, there were few differences between distinct dual‐pathogen pairs and their respective mono‐pathogen counterparts.

Conclusion

A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono‐pathogen indicate the likely presence of complex microbial interactions between the various pathogens.
Hemodynamic and Symptomatic Consequences of Ventricular Pacing*
Authors: Nishimura Rick A. , Gersh Bernard J. , Vlietstra Ronald E. , Osborn Michael J. , Ilstrup Duane M. , Holmes David R.
Published: April 2015

NISHIMURA, R.A. et al.: Hemodynamic and symptomatic consequences of ventricular pacing. After implantation of a ventricular demand pacemaker (VVI), occasional patients continue to have dizziness, syncope, or near syncope (“pacemaker syndrome”). To identify patients in whom VVI pacing may have deleterious effects, we compared cuff blood pressure responses to VVI pacing with blood pressure responses to atrioventricsler sequential pacing (DVI) or sinus rhythm in 50 consecutive patients. Patients with intact ventriculoatrial conduction had a much greater decrease in systolic blood pressure with VVI pacing (24 ± 11 mm Hg) than those with ventriculoatrial dissociation (−4 ± 15 mm Hg) (P<0.005). Patients who were in heart failure had a lesser decrease in blood pressure with VVI pacing than did those without failure (P<0.05); 13 of the 14 heart failure patients lacked ventriculoatrial conduction. Ten patients had symptomatic dizziness after VVI pacing; the incidence of symptoms was higher in patients with ventriculoatrial conduction (9 of 23) than in those without ventriculoatrial conduction (1 of 27) (P<0.003). We conclude that the presence of intact ventriculoatrial conduction appears to be a crucial determinent of the hemodynamic response to VVI pacing, and its presence may identify patients who are at risk for “pacemaker syndrome.”
Identifying Children with Intellectual Disabilities in the Tribal Population of Barwani District in State of Madhya Pradesh, India
Authors: Lakhan Ram , Mawson Anthony R.
Published: April 2015

Background

Low‐and middle‐income countries (LAMI) lack an integrated and systematic approach to identify people with intellectual disabilities. Screening surveys are considered resource‐intensive; therefore, alternative approaches are needed. This study attempted to identify children up to age 18 years with intellectual disabilities through a mixed‐method approach involving focus group interviews (FGIs) and door‐to‐door surveys.

Materials and Methods

Focus groups were conducted with the assistance and involvement of local leaders in four villages of Barwani district of Madhya Pradesh with a 99% tribal population in all four villages. A formal survey of the community was then conducted to determine the prevalence of intellectual disabilities based on a standardized screening instrument (NIMH‐DDS).

Results

Thirty focus group interviews were conducted involving 387 participants (males 284, females 103) over a period of 13 days. The entire adult population (N = 8797) was then surveyed for intellectual disabilities using a standardized screening instrument. The data revealed a close similarity in the prevalence rates of intellectual disabilities, as determined by the two approaches (Focus Group Interviews, 5.22/1000 versus Survey, 5.57/1000).

Conclusion

A qualitative method using FGIs successfully identified people with intellectual disabilities in an economically deprived tribal area, showing that a community‐based approach provides a close estimate of intellectual disabilities based on a formal survey using standard diagnostic criteria. These data suggest that FGI, along with other qualitative data, could be helpful in designing and in serving as an entree for community‐based interventions.
CEO's Operating Ability and the Association between Accruals and Future Cash Flows
Authors: Choi Wooseok , Han Sam , Jung Sung Hwan , Kang Tony
Published: April 2015

This study investigates whether an individual CEO's operating ability, operationalized as the extent to which an individual CEO utilizes the company's assets efficiently to generate profits, explains the association between accruals and future cash flows. While this mapping can be driven by both the quality of accounting measurement and CEO operating ability, there is little empirical evidence on the latter link. After controlling for the CEO's accounting estimation ability, we find that the association between current period accruals and future cash flows is stronger when the CEO demonstrates superior operating ability. This suggests that a CEO's operating ability is an important determinant of the informativeness of current accruals for future cash flows.
The biodiversity and genetic structure of Balearic sheep breeds
Authors: Pons A.L. , Landi V. , Martinez A. , Delgado J.V.
Published: April 2015

The Balearic sheep breeds, Mallorquina, Menorquina, Roja Mallorquina, Ibicenca and one possible new genetic group, Formentera, constitute a unique genetic resource in the Mediterranean farming landscape, displaying high genetic diversity levels and being well differentiated among themselves and with respect to the continental sheep breeds. We used a microsatellite panel of markers to study genetic diversity and relationships with other Spanish breeds. The results reported in this study have important implications for the use, conservation and breeding of Balearic sheep stocks. A mean number of 7.59 alleles was found among the Balearic sheep breeds for the microsatellites scored. The whole mean value of observed heterozygosity amounted to 0.62, whereas the expected heterozygosity value was 0.69, suggesting the presence of a great degree of genetic variability, although a significant deficit of heterozygotes was detected for some markers. Genetic distance estimates showed that Balearic sheep are differentiated from the other Spanish breeds and in particular, from the Merino type. The Ibicenca breed showed the highest distance value from other breeds. The neighbour‐net method of analysis clustered the Roja Mallorquina, Menorquina and Mallorquina breeds. The Structure results clearly demonstrated the genetic differentiation among the four Balearic sheep breeds, with the Ibicenca and Formentera races joined, with slight migration among them. Few external genetic influences from the Spanish mainland breeds were detected.