bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut‐allergic mice
Authors: Kulis M. , Chen X. , Lew J. , Wang Q. , Patel O. P. , Zhuang Y. , Murray K. S. , Duncan M. W. , Porterfield H. S. , W. Burks A. , Dreskin S. C.
Published: January 2012

Background

Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut allergic sera.

Objectives

To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE.

Methods

An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood.

Results

Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P < 0.05) and a smaller decrease in body temperature (P < 0.01). Results with the basophil histamine release assay corroborated these findings (P < 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut‐allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP‐1) release compared with placebo (P < 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges.

Conclusions and Clinical Relevance

Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut‐allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.
What is severe asthma?
Authors: Blakey J. D. , Wardlaw A. J.
Published: January 2012

Asthma is common, and some individuals are severely affected by it. Learned institutions have sought to provide a definition of ‘severe asthma’ to facilitate research and clinical care. This is a challenging undertaking given the difficulty in defining asthma and the lack of supportive evidence for a distinct severe asthma phenotype. In this review, we discuss the rationale for a definition of severe asthma and the relative merits of the sequential attempts that have been made to produce such a definition. The difficulty in disentangling control and severity is highlighted, as is the heterogeneity of phenotype in severe asthma, and potential for misclassification. We conclude that the search for a singular definition of severe asthma is problematic, though likely to continue. We suggest the alternative strategy of using classifiers with a specific aim related to symptoms, pathophysiology or service provision.
Effects of zooplankton dynamics on epilimnetic phosphorus loss
Authors: PITSCH MATTHIAS , AWASSI VIVIANE , SUSKO EMILY , HÜLSMANN STEPHAN
Published: January 2012

1. Our aim was to analyse the impact of zooplankton dynamics on the relative importance of two mechanisms contributing to the loss of phosphorus (P) from the epilimnion of stratified lakes: net population incorporation into zooplankton biomass and P sedimentation.

2. We established enclosures without Daphnia (control), with a growing Daphnia population (treatment D) and with a high, stable Daphnia population (treatment D+). The P incorporated in zooplankton biomass and sedimented was measured at short intervals over a period of 17 days.

3. In both Daphnia treatments, sedimentation increased and the P content of sedimented matter was higher than in the control and highest in D+. The P loss by sedimentation between day 3 and 17 was generally high (>25%, >1.8% day−1) with particularly high values in D+ (∼60%, 4.3% day−1). Phosphorus sedimentation was higher in the zooplankton treatments, although the contribution of exuviae and dead Daphnia was minor. Faecal material was probably a major component of sedimentation.

4. By contrast, the amount of P in zooplankton (mainly Daphnia) biomass increased in D but remained constant in D+. Phosphorus loss owing to net population incorporation was generally low and ranged up to 6.5% (0.5% day−1) in treatment D. A positive relationship between Daphnia dry mass and P sedimentation, as well as P incorporation, was found.

5. Sedimentation is evidently an important cause of P loss from the epilimnion where Daphnia is abundant. By contrast, P incorporation into Daphnia biomass may only become an important loss factor when the population is growing.
The use of cone‐beam computed tomography and virtual reality simulation for pre‐surgical practice in endodontic microsurgery
Authors: Suebnukarn S. , Rhienmora P. , Haddawy P.
Published: January 2012

Suebnukarn S, Rhienmora P, Haddawy P. The use of cone‐beam computed tomography and virtual reality simulation for pre‐surgical practice in endodontic microsurgery. International Endodontic Journal, 45, 627–632, 2012.

Aim  To design and evaluate the impact of virtual reality (VR) pre‐surgical practice on the performance of actual endodontic microsurgery.

Methodology  The VR system operates on a laptop with a 1.6‐GHz Intel processor and 2 GB of main memory. Volumetric cone‐beam computed tomography (CBCT) data were acquired from a fresh cadaveric porcine mandible prior to endodontic microsurgery. Ten inexperienced endodontic trainees were randomized as to whether they performed endodontic microsurgery with or without virtual pre‐surgical practice. The VR simulator has microinstruments to perform surgical procedures under magnification. After the initial endodontic microsurgery, all participants served as their own controls by performing another procedure with or without virtual pre‐surgical practice. All procedures were videotaped and assessed by two independent observers using an endodontic competency rating scale (from 6 to 30).

Results  A significant difference was observed between the scores for endodontic microsurgery on molar teeth completed with virtual pre‐surgical practice and those completed without virtual presurgical practice, median 24.5 (range = 17–28) versus median 18.75 (range = 14–26.5), P = 0.041. A significant difference was observed between the scores for osteotomy on a molar tooth completed with virtual pre‐surgical practice and those completed without virtual pre‐surgical practice, median 4.5 (range = 3.5–4.5) versus median 3 (range = 2–4), P = 0.042.

Conclusions  Pre‐surgical practice in a virtual environment using the 3D computerized model generated from the original CBCT image data improved endodontic microsurgery performance.
Abnormal repetitive behaviours: shared phenomenology and pathophysiology
Authors: Muehlmann A. M. , Lewis M. H.
Published: January 2012

Background  Self‐injurious behaviour (SIB) is a devastating problem observed in individuals with various neurodevelopmental disorders, including specific genetic syndromes as well as idiopathic intellectual and developmental disability. Although an increased prevalence of SIB has been documented in specific genetic mutations, little is known about the neurobiological basis of SIB. This makes vulnerability assessment and pharmacological treatment incredibly challenging.

Method  Here we review evidence that SIB and other repetitive, invariant behaviours, such as stereotypy, compulsions and tics, share many phenotypic similarities, are often co‐morbidly expressed and have common inducing conditions. This argues for shared or overlapping pathophysiology. As much more is known about the neurobiology of these related disorders, this should make the neurobiology of SIB a more tractable problem.

Results  Stereotypy, compulsions and tics are diagnostic for disorders that have received focused neurobiological investigation (autism, obsessive compulsive disorder, Tourette syndrome, respectively). In addition, animal models of these repetitive behaviours have been well characterised. Collectively, these studies have found that cortical basal ganglia circuitry dysfunction mediates repetitive behaviour. Moreover, these studies provide more detailed information and potentially testable hypotheses about specific aspects of the circuitry that may be operative in SIB.

Conclusions  We can use available information from clinical and animal models to make more precise hypotheses regarding the particular pathophysiology driving SIB. The results of testing such hypotheses should generate pharmacological strategies that may prove efficacious in reducing SIB.
Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats
Authors: ZONCA A. , RAVASIO G. , GALLO M. , MONTESISSA C. , CARLI S. , VILLA R. , CAGNARDI P.
Published: January 2012

Zonca, A., Ravasio, G., Gallo, M., Montesissa, C., Carli, S., Villa, R., Cagnardi, P. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats. J. vet. Pharmacol. Therap. 35, 580–587.

The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as ‘ketofol’, frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV‐visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two‐compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half‐life (t1/2λ2 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half‐life (t1/2λ2 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol’s long elimination half‐life and low clearance is negligible when the drug is administered as short‐term and low‐dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism.
Role of monokine induced by interferon‐γ in liver injury induced by hepatitis B virus in mice
Authors: Xia Y. J. , Zeng D. , Xia L. M. , Yu F. , Lin H. H. , Zhou L. , Tian D. A. , Liu M.
Published: January 2012

Summary.  The chemokine monokine induced by interferon‐γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)‐κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome‐containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad‐HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF‐κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3‐kinase/Akt, extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo‐jetPEI‐Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF‐κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3‐kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.
Cascade stomach is associated with upper gastrointestinal symptoms: a population‐based study
Authors: Kusano M. , Hosaka H. , Moki H. , Shimoyama Y. , Kawamura O. , Kuribayashi S. , Mori M. , Akuzawa M.
Published: January 2012

Background  Cascade stomach (CS) is recognized by characteristic findings on barium studies. We prospectively investigated the relationship between CS and upper gastrointestinal (GI) symptoms.

Methods  In subjects undergoing health screening, CS was diagnosed by barium studies. Consecutive persons (500 men and 127 women) with CS were identified and the same number of age‐matched subjects without CS were selected as controls. Upper GI symptoms were classified as reflux symptoms, dyspepsia symptoms, or epigastralgia symptoms. Then, we prospectively analyzed barium studies to classify the gastric morphology and also assessed upper GI symptoms in consecutive 5008 men and 2736 women.

Key Results  BMI was significantly higher in men with CS than in controls, and also in women with CS than in controls. Upper GI symptoms were significantly more frequent in the CS group than the controls among both men and women, especially reflux symptoms. In men, logistic regression analysis identified CS as an independent risk factor for upper GI symptoms (odds ratio = 1.771, P = 0.005) and for reflux symptoms (odds ratio = 2.07, P = 0.009). In women, CS was also significantly related to upper GI symptoms (odds ratio = 2.544, P = 0.020). The prevalence of CS was significantly higher (P < 0.0001) among symptomatic men than among those with no symptoms.

Conclusions & Inferences  Gastric morphology is related to upper GI symptoms in both men and women. Cascade stomach should be reconsidered as a pathophysiological factor associated with upper GI symptoms.
The deceased organ donor with an “open abdomen”: proceed with caution
Authors: Watkins A.C. , Vedula G.V. , Horan J. , Dellicarpini K. , Pak S.‐W. , Daly T. , Samstein B. , Kato T. , Emond J.C. , Guarrera J.V.
Published: January 2012

In solid organ transplantation, the disparity between donor supply and patients awaiting transplant continues to increase. The organ shortage has led to relaxation of historic contraindications to organ donation. A large percentage of deceased organ donors have been subjected to traumatic injuries, which can often result in intervention that leads to abdominal packing and intensive care unit resuscitation. The donor with this “open abdomen” (OA) presents a situation in which the risk of organ utilization is difficult to quantify. There exists a concern for the potential of a higher risk for both bacterial and fungal infections, including multidrug‐resistant (MDR) pathogens because of the prevalence of antibiotic use and critical illness in this population. No recommendations have been established for utilization of organs from these OA donors, because data are limited. Herein, we report a case of a 21‐year‐old donor who had sustained a gunshot wound to his abdomen, resulting in a damage‐control laparotomy and abdominal packing. The donor subsequently suffered brain death, and the family consented to organ donation. A multiorgan procurement was performed with respective transplantation of the procured organs (heart, liver, and both kidneys) into 4 separate recipients. Peritoneal swab cultures performed at the time of organ recovery grew out MDR Pseudomonas aeruginosa on the day after procurement, subsequently followed by positive blood and sputum cultures as well. All 4 transplant recipients subsequently developed infections with MDR P. aeruginosa, which appeared to be donor‐derived with similar resistance patterns. Appropriate antibiotic coverage was initiated in all of the patients. Although 2 of the recipients died, mortality did not appear to be clearly associated with the donor‐derived infections. This case illustrates the potential infectious risk associated with organs from donors with an OA, and suggests that aggressive surveillance for occult infections should be pursued.
Summer season and long‐term drought increase the richness of bacteria and fungi in the foliar phyllosphere of Quercus ilex in a mixed Mediterranean forest
Authors: Peñuelas J. , Rico L. , Ogaya R. , Jump A. S. , Terradas J.
Published: January 2012

We explored the changes in richness, diversity and evenness of epiphytic (on the leaf surface) and endophytic (within leaf tissues) bacteria and fungi in the foliar phyllosphere of Quercus ilex, the dominant tree species of Mediterranean forests. Bacteria and fungi were assessed during ontogenic development of the leaves, from the wet spring to the dry summer season in control plots and in plots subjected to drought conditions mimicking those projected for future decades. Our aim was to monitor succession in microbiota during the colonisation of plant leaves and its response to climate change. Ontogeny and seasonality exerted a strong influence on richness and diversity of the microbial phyllosphere community, which decreased in summer in the whole leaf and increased in summer in the epiphytic phyllosphere. Drought precluded the decrease in whole leaf phyllosphere diversity and increased the rise in the epiphytic phyllosphere. Both whole leaf bacterial and fungal richness decreased with the decrease in physiological activity and productivity of the summer season in control trees. As expected, the richness of epiphytic bacteria and fungi increased in summer after increasing time of colonisation. Under summer dry conditions, there was a positive relationship between TRF (terminal restriction fragments) richness and drought, both for whole leaf and epiphytic phyllosphere, and especially for fungal communities. These results demonstrate that changes in climate are likely to significantly alter microbial abundance and composition of the phyllosphere. Given the diverse functions and large number of phyllospheric microbes, the potential functional implications of such community shifts warrant exploration.
The dicotyledonous NAD malic enzyme C4 plant Cleome gynandra displays age‐dependent plasticity of C4 decarboxylation biochemistry
Authors: Sommer M. , Bräutigam A. , Weber A. P. M.
Published: January 2012

The C4 photosynthetic pathway enriches carbon dioxide in the vicinity of Rubisco, thereby enabling plants to assimilate carbon more efficiently. Three canonical subtypes of C4 exist, named after their main decarboxylating enzymes: NAD‐dependent malic enzyme type, NADP‐dependent malic enzyme type and phosphoenolpyruvate carboxykinase type. Cleome gynandra is known to perform NAD‐ME type C4 photosynthesis. To further assess the mode of C4 in C. gynandra and its manifestation in leaves of different age, total enzyme activities of eight C4‐related enzymes and the relative abundance of 31 metabolites were measured. C. spinosa was used as a C3 control. C. gynandra was confirmed as an NAD‐ME type C4 plant in mid‐aged leaves, whereas a mixed NAD‐ME and PEPCK type was observed in older leaves. Young leaves showed a C3‐C4 intermediate state with respect to enzyme activities and metabolite abundances. Comparative transcriptome analysis of mid‐aged leaves of C. gynandra and C. spinosa showed that the transcript of only one aspartate aminotransferase (AspAT) isoform is highly abundant in C. gynandra. However, the canonical model of the NAD‐ME pathway requires two AspATs, a mitochondrial and a cytosolic isoform. Surprisingly, our results indicate the existence of only one highly abundant AspAT isoform. Using GFP‐fusion, this isozyme was localised exclusively to mitochondria. We propose a revised model of NAD‐ME type C4 photosynthesis in C. gynandra, in which both AspAT catalysed reactions take place in mitochondria and PEPCK catalyses an alternative decarboxylating pathway.
A dithiol glutaredoxin cDNA from sweet potato (Ipomoea batatas [L.] Lam): enzyme properties and kinetic studies
Authors: Chi X.‐W. , Lin C.‐T. , Jiang Y.‐C. , Wen L. , Lin C.‐T.
Published: January 2012

Glutaredoxins (Grx) play an important role in reduction of protein glutathione mixed disulphides. An IbGrx cDNA (561 bp, EF362614) encoding a putative dithiol Grx was cloned from sweet potato (Ipomoea batatas [L.] Lam). The deduced amino acid sequence is conserved among the reported dithiol Grx, having a CGYC dithiol motif at the active site. A 3‐D structural model was created based on the known crystal structure of a poplar Grx (GrxC1). To characterise the IbGrx protein, the coding region was subcloned into an expression vector and transformed into Escherichia coli. The recombinant His6‐tagged IbGrx was expressed and purified by metal affinity chromatography. The purified enzyme showed a monomeric band, as demonstrated with 15% SDS‐PAGE. The Michaelis constant (KM) for ß‐hydroxyethyl disulphide (HED) was 0.50 ± 0.08 Mm. The enzyme retained 60% activity at 80 °C for 16 min. The enzyme was active over a broad pH range from 6.0 to 11.0, and in the presence of imidazole up to 0.4 M. The enzyme was susceptible to protease.
Inhibition of actin polymerisation by low concentration Latrunculin B affects endocytosis and alters exocytosis in shank and tip of tobacco pollen tubes
Authors: Moscatelli A. , Idilli A. I. , Rodighiero S. , Caccianiga M.
Published: January 2012

Pollen tube growth depends on the integrity of the actin cytoskeleton that regulates cytoplasmic streaming and secretion. To clarify whether actin also plays a role in pollen tube endocytosis, Latrunculin B (LatB) was employed in internalisation experiments with tobacco pollen tubes, using the lipophilic dye FM4‐64 and charged nanogold. Time‐lapse analysis and dissection of endocytosis allowed us to identify internalisation pathways with different sensitivity to LatB. Co‐localisation experiments and ultrastructural observations using positively charged nanogold revealed that LatB significantly inhibited endocytosis in the pollen tube shank, affecting internalisation of the plasma membrane (PM) recycled for secretion, as well as that conveyed to vacuoles. In contrast, endocytosis of negatively charged nanogold in the tip, which is also conveyed to vacuoles, was not influenced. Experiments of fluorescence recovery after photobleaching (FRAP) of the apical and subapical PM revealed domains with different rates of fluorescence recovery and showed that these differences depend on the actin cytoskeleton integrity. These results show the presence of distinct degradation pathways by demonstrating that actin‐dependent and actin‐indepedent endocytosis both operate in pollen tubes, internalising tracts of PM to be recycled and broken down. Intriguingly, although most studies concentrate on exocytosis and distension in the apex, the present paper shows that uncharacterised, actin‐dependent secretory activity occurs in the shank of pollen tubes.
Self‐efficacy and self‐care behavior of Malaysian patients with type 2 diabetes: a cross sectional survey
Authors: Sharoni Siti Khuzaimah Ahmad , Wu Shu‐Fang Vivienne
Published: January 2012

This study investigated the association between self‐efficacy and self‐care behavior to determine the degree of self‐efficacy and to examine differences in self‐efficacy according to patient variables, including state of health, of Malaysian patients with type 2 diabetes. The sample comprised 388 patients (respondents). We collected the data from December 2010 to February 2011. We found a significant positive relationship between self‐efficacy and self‐care behavior (rs = 0.481, P < 0.001). The degree of self‐efficacy was moderately high (mean = 7.570). We found significant differences between self‐efficacy and education level (Wilk's Lambda = 0.918, F[12, 1008] = 2.779, P < 0.05), duration of diabetes (Wilk's Lambda = 0.954, F[8, 736] = 2.264, P < 0.05), other chronic conditions (Wilk's Lambda = 0.967, F[4, 383] = 3.304, P < 0.05) and diabetic complications (Wilk's Lambda = 0.963, F[4, 383] = 3.653, P < 0.05). Self‐efficacy can be used as a model to understand self‐care behavior. Individualized nursing interventions based on self‐efficacy theory should be utilized in high risk diabetic patients so as to assist and improve self‐care behavior.
Molecular phylogeny of the marine littoral genus Cafius (Coleoptera: Staphylinidae: Staphylininae) and implications for classification
Authors: Jeon Mi‐Jeong , Song Jeong‐Hun , Ahn Kee‐Jeong
Published: January 2012

Jeon, M.‐J., Song, J.‐H. & Ahn, K.‐J. (2012). Molecular phylogeny of the marine littoral genus Cafius (Coleoptera: Staphylinidae: Staphylininae) and implications for classification. —Zoologica Scripta, 41, 150–159.

A phylogenetic analysis of the marine littoral genus Cafius Stephens is presented based on molecular characters. The data set comprised partial mitochondrial COI (910 bp), COII (369 bp), 12S rDNA (351–354 bp), 16S rDNA (505–509 bp) and nearly complete sequences of 18S rDNA (1814–1830 bp) for 37 species. Twenty‐seven Cafius species, representing five of six subgenera, two Remus Holme species, three Phucobius Sharp species, monotypic Thinocafius Steel and four outgroups were included. The sequences were analysed simultaneously by parsimony analysis in Tree Analysis Using New Technology (TNT) with traditional manual alignment, direct optimization (DO) in the program POY4 under a variety of gap costs and partitioned Bayesian analysis for the combined data. The genus Cafius and nearly all of its subgenera were not supported as being monophyletic. Instead, all analyses (parsimony trees, DO tree under equal weighting and Bayesian tree) showed monophyly of Cafius + Phucobius + Remus + Thinocafius (clade Z) and all seven nested clades (A–G). However, the phylogenetic relationships among clades A–G differed among the analyses. The genus Phucobius was recovered as a monophyletic group within Cafius. The genus Remus was not monophyletic but formed a clade with C. rufescens Sharp and C. rufifrons Bierig within Cafius. The genus Thinocafius formed a clade with C. caviceps Broun, C. litoreus (Broun) and C. quadriimpressus (White) within Cafius. We propose new concepts for the genus Cafius and its related genera, and the seven nested clades.
Increased non‐prostate cancer death risk in clinically diagnosed prostate cancer
Authors: van Leeuwen Pim J. , Otto Suzie J. , Kranse Ries , Roobol Monique J. , Bul Meelan , Zhu Xiaoye , de Koning Harry , Schröder Fritz H.
Published: January 2012

Study Type – Prognosis (case control)

Level of Evidence 3a

What's known on the subject? and What does the study add?

Treatment of advanced PC might put patients at an increased risk of cardiovascular events. Recent studies have suggested that the excess mortality is lower among men who were diagnosed with screen detected PC in comparison to men with clinically diagnosed PC, possibly due to the use of medications for cardiovascular disease and the change to a healthier lifestyle of men with a screen detected PC.

Men with clinically diagnosed PC have an increased risk of death unrelated to PC itself, i.e., the excess mortality is based on an increased risk of dying from other neoplasm and diseases of the circulatory or respiratory system.

OBJECTIVE

To assess the cause‐specific mortality unrelated to prostate cancer (PC) itself in patients with screen‐ and clinically diagnosed PC.

PATIENTS AND METHODS

The present study was conducted among participants of the European Randomized Study of Screening for Prostate Cancer.

Based on consensus of the causes of death committee (CODC), all patients who died from PC were excluded.

In the intervention arm, cases were patients with a screen‐detected PC, aged 55–74 years, between 1993 and 2001.

These cases were matched to two controls in whom no cancer was found after biopsy, and two controls in whom no cancer was suspected after screening. In the control arm, cases were patients with clinically diagnosed PC, aged 55–74 years, between 1993 and 2001. These cases were matched to four controls without PC. Matching was done with respect to date of birth, screening and/or diagnosis. Men were followed up to 31 December 2007.

RESULTS

No statistically significant difference in overall mortality between cases and controls in the intervention arm was observed: relative risk (RR) 1.26 (95% confidence interval [CI] 0.96–1.65; P = 0.102) and RR 1.13 (95% CI 0.86–1.47; P = 0.381).

In the control arm, the overall mortality was statistically significantly higher in cases relative to controls: RR 1.43 (95% CI 1.03–2.00; P = 0.033).

This difference was because of an increased risk of dying from neoplasms and disease of the circulatory or respiratory system among cases: RR 1.61 (95% CI 1.12–2.29; P = 0.009).

The present study was limited by the relatively small sample size.

CONCLUSIONS

Increased mortality unrelated to PC itself was observed in men with clinically diagnosed PC, but not in screen‐detected PC.

The excess mortality in men with clinically diagnosed PC seems to be as a result of a significantly increased risk of dying from neoplasm and disease of the circulatory or respiratory system.

Results have to be studied more thoroughly in further clinical trials.
GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression
Authors: Peters Inga , Eggers Hendrik , Atschekzei Faranaz , Hennenlotter Jörg , Waalkes Sandra , Tränkenschuh Wolfgang , Großhennig Anika , Merseburger Axel S. , Stenzl Arnulf , Kuczyk Markus A. , Serth Jürgen
Published: January 2012

What's known on the subject? and What does the study add?

GATA5 CpG island (CGI) methylation and transcriptional inactivation is involved in colorectal and gastric cancer. Whether DNA methylation of GATA5 affects clinical pathology is still unclear. In the present study, we analysed, for the first time, CGI methylation in RCC and its association with clinicopathological parameters and progression‐free survival of patients.

We show for the first time GATA5 CGI hypermethylation in RCC. Moreover, we found out that increased methylation is statistically associated with status of metastasis, progressive disease and shortened progression‐free survival. The present study underline the necessity for further functional investigations as well as prospective survival analyses to clarify whether GATA5 promoter methylation can provide independent information for future clinical management of patients with RCC.

OBJECTIVE

To investigate whether GATA5 CpG island (CGI) methylation occurs in renal cell carcinoma (RCC) and is associated with clinical, histopathological characteristics or progression‐free survival of patients.

PATIENTS AND METHODS

Methylation was quantified in 117 RCC samples and 89 paired adjacent normal tissues using quantitative combined bisulphite restriction analysis (COBRA).

COBRA was evaluated in advance by pyrosequencing analyses of control RCC cell lines (coefficient of correlation, R= 0.95).

Statistical analyses were carried out using the paired t‐test for matched tumour tissue (TU) and adjacent normal tissue (adN) samples, logistic regression for comparisons of independent sample groups and Cox regression for analysis of progression‐free survival.

RESULTS

In the present study, we found a significant higher mean relative methylation in TU (20.4%) than in adN (7.9%, P < 0.001) in paired samples of all RCCs.

Increased GATA5 methylation in tumours was associated with metastasis (P= 0.005) and decreased progression‐free survival (P= 0.005, HR = 4.59) in the clear‐cell RCC (ccRCC) group.

CGI methylation in advanced ccRCCs (pT ≥3 and/or N1, M1 or G2–3/G3) exceeds those detected in localized tumours (pT ≤2, N0, M0, G1/G1–2) (27.8% vs 11.0%, P < 0.001).

CONCLUSIONS

The association of GATA5 hypermethylation with metastasis and progression‐free survival of patients indicates that epigenetic alterations of GATA5 participate in renal cell carcinogenesis.

Moreover, GATA5 CGI methylation could serve as a biomarker for tumour progression, although prospective and functional investigations are necessary to clarify whether independent information for future clinical management of patients with RCC can be obtained.
Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function
Authors: Forst T. , Michelson G. , Ratter F. , Weber M. M. , Anders S. , Mitry M. , Wilhelm B. , Pfützner A.
Published: January 2012

Diabet. Med. 29, 1115–1118 (2012)

Aims  The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy.

Methods  Forty‐four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA1c < 53 mmol/mol (7.0%), age 30–65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelial function and arterial stiffness were measured.

Results  HbA1c levels declined from 45 ± 4 mmol/mol (6.3 ± 0.4%; mean ± sd) to 40 ± 3 mmol/mol (5.8 ± 0.3%) during liraglutide treatment. Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 μmol/l, E‐selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml, plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment. The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5% after 6 weeks and to 11.1 ± 9.9% after 12 weeks. No change could be observed for high‐sensitivity C‐reactive protein, monocyte chemotactic protein 1, vascular cell adhesion molecule or arterial stiffness parameters.

Conclusions  In patients with Type 2 diabetes, well controlled with metformin monotherapy, addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control.
Adolescent Daily and General Maladjustment: Is There Reactivity to Daily Repeated Measures Methodologies?
Authors: Nishina Adrienne
Published: January 2012

The present study examined whether repeated exposure to daily surveys about negative social experiences predicts changes in adolescents’ daily and general maladjustment, and whether question content moderates these changes. Across a 2‐week period, 6th‐grade students (N = 215; mode age = 11) completed 5 daily reports tapping experienced or experienced and witnessed negative events, or they completed no daily reports. General maladjustment was measured in 2‐week intervals before, at the end of, and 2 weeks after the daily report study. Daily maladjustment either decreased or did not change across the 5 daily report exposures. General maladjustment decreased across the three 2‐week intervals. Combined, results indicate that short‐term daily report studies do not place youth at risk for increased maladjustment.
Intellectual Interest Mediates Gene × Socioeconomic Status Interaction on Adolescent Academic Achievement
Authors: Tucker‐Drob Elliot M. , Harden K. Paige
Published: January 2012

Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this Gene × Environment interaction. One process may involve the conversion of intellectual interest into academic achievement. Analyses of data from 777 pairs of 17‐year‐old twins indicated that Gene × SES effects on achievement scores can be accounted for by stronger influences of genes for intellectual interest on achievement at higher levels of SES. These findings are consistent with the hypothesis that higher SES affords greater opportunity for children to seek out and benefit from learning experiences that are congruent with their genetically influenced intellectual interests.
Constrained Multiobjective Designs for Functional Magnetic Resonance Imaging Experiments Via a Modified Non-Dominated Sorting Genetic Algorithm
Authors: Kao Ming-Hung , Mandal Abhyuday , Stufken John
Published: January 2012

Functional magnetic resonance imaging (MRI) is an advanced technology for studying brain functions. Owing to the complexity and high cost of functional MRI experiments, high quality multiobjective functional MRI designs are in great demand; they help to render precise statistical inference and are keys to the success of functional MRI experiments. Here, we propose an efficient approach for obtaining multiobjective functional MRI designs. In contrast with existing methods, the approach proposed does not require users to specify weights for the different objectives and can easily handle constraints to fulfil customized requirements. Moreover, the underlying statistical models that we consider are more general. We can thus obtain designs for cases where brief, long or varying stimulus durations are utilized. The usefulness of our approach is illustrated by using various experimental settings.
Predicting how adaptation to climate change could affect ecological conservation: secondary impacts of shifting agricultural suitability
Authors: Bradley Bethany A. , Estes Lyndon D. , Hole David G. , Holness Stephen , Oppenheimer Michael , Turner Will R. , Beukes Hein , Schulze Roland E. , Tadross Mark A. , Wilcove David S.
Published: January 2012

Aim:  Ecosystems face numerous well‐documented threats from climate change. The well‐being of people also is threatened by climate change, most prominently by reduced food security. Human adaptation to food scarcity, including shifting agricultural zones, will create new threats for natural ecosystems. We investigated how shifts in crop suitability because of climate change may overlap currently protected areas (PAs) and priority sites for PA expansion in South Africa. Predicting the locations of suitable climate conditions for crop growth will assist conservationists and decision‐makers in planning for climate change.

Location:  South Africa.

Methods:  We modelled climatic suitability in 2055 for maize and wheat cultivation, two extensively planted, staple crops, and overlaid projected changes with PAs and PA expansion priorities.

Results:  Changes in winter climate could make an additional 2 million ha of land suitable for wheat cultivation, while changes in summer climate could expand maize suitability by up to 3.5 million ha. Conversely, 3 million ha of lands currently suitable for wheat production are predicted to become climatically unsuitable, along with 13 million ha for maize. At least 328 of 834 (39%) PAs are projected to be affected by altered wheat or maize suitability in their buffer zones.

Main conclusions:  Reduced crop suitability and food scarcity in subsistence areas may lead to the exploitation of PAs for food and fuel. However, if reduced crop suitability leads to agricultural abandonment, this may afford opportunities for ecological restoration. Expanded crop suitability in PA buffer zones could lead to additional isolation of PAs if portions of newly suitable land are converted to agriculture. These results suggest that altered crop suitability will be widespread throughout South Africa, including within and around lands identified as conservation priorities. Assessing how climate change will affect crop suitability near PAs is a first step towards proactively identifying potential conflicts between human adaptation and conservation planning.
Population Growth and Endogenous Technological Change: Australian Economic Growth in the Long Run*
Authors: BANERJEE RAJABRATA
Published: January 2012

The Australian growth experience appears to be a three‐act phenomenon with higher per capita income and living standards before 1890 and after 1940, disconnected by a 50‐year period of no trend improvement in between. This article examines the roles of technological progress and population growth in Australian productivity growth since 1870. The empirical results confirm the three‐act growth experience by Australia, and while population growth had a negative effect, innovative activity had a positive effect on productivity growth. Furthermore, the estimates strongly support the Schumpeterian growth hypothesis, which predicts that productivity growth is driven by the level of research intensity in the economy.
Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons
Authors: Evans Miles Steven , Cheng Xiangying , Jeffry Joseph A. , Disney Kimberly E. , Premkumar Louis S.
Published: January 2012

(Headache 2012;52:773‐784)

Objective.— To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors.

Background.— TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia, TRPV1‐containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system.

Methods.— We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole‐cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole‐cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI.

Results.— Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, in trigeminal ganglion, and in the TNC. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings, and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 µM), a selective antimigraine drug, inhibited TRPV1‐mediated inward currents in TG and capsaicin‐elicited spontaneous excitatory postsynaptic currents in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI‐labeled TG neurons innervating cerebral dura.

Conclusion.— Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache.
Pediatric Headache: A Clinical Review
Authors: Jacobs Howard , Gladstein Jack
Published: January 2012

In this review we describe the epidemiology, classification, and approach to the diagnosis and treatment of episodic and chronic migraine in children. We review both traditional and alternative medications, and offer a glimpse into the future of pediatric headache.
Characteristics, Services, and Infection Control Practices of New York City Assisted Living Facilities, 2010
Authors: Stachel Anna G. , Bornschlegel Katherine , Balter Sharon
Published: January 2012

Objectives

To describe New York City (NYC) assisted living facility (ALF) characteristics, services offered, and infection control practices and to identify infection control barriers and unmet needs.

Design

Cross‐sectional.

Setting

ALFs licensed or applying to be licensed in NYC.

Participants

Seventy ALFs; 70 of 77 eligible facilities participated (91% participation rate).

Measurements

Telephone interview questions assessed ALF characteristics, services offered, and infection control practices, including glucometry practices.

Results

ALFs provided a broad range of services, such as vaccination (90%), assistance with taking medication (75%), bathing and showering (33%), and blood glucose monitoring (90%). Ninety percent of the facilities had nurses on site (directly employed or through a contract agency). Five facilities reported that residents sometimes shared glucometers, and one reported that fingerstick devices were sometimes shared. The majority of facilities wanted educational materials for staff (83%) and residents (77%) on topics including influenza, respiratory illness, norovirus, standard precautions, and general infection control. ALFs had a range of sick leave policies and infection control training requirements. Eighty‐nine percent of the facilities reported having designated staff responsible for infection control, although 50% had nonclinical job titles.

Conclusion

NYC ALFs were varied in terms of nursing services offered, characteristics, and residents’ needs; therefore, public health agencies may need to be flexible in their assistance. Public health agencies should consider strengthening relationships with ALFs to identify unmet needs and gaps in services.
Effects of a Late‐Life Suicide Risk–Assessment Training on Multidisciplinary Healthcare Providers
Authors: Huh Joung T. , Weaver Christopher M. , Martin Jennifer L. , Caskey Nicholas H. , O'Riley Alisa , Kramer Betty Josea
Published: January 2012

Older adults are among the highest at risk for completing suicide, and they are more likely to seek mental health services from providers outside of traditional mental health care, but providers across the spectrum of care have limited training in suicide risk assessment and management and particularly lack training in suicide prevention for older adults. An educational program was developed to increase awareness and improve suicide risk assessment and management training for a range of healthcare providers who may see older adults in their care settings. One hundred thirty‐two participants from two Veterans Affairs Medical Centers participated in a 6.5‐hour‐long workshop in the assessment and management of suicide risk in older adults. Participants were asked to complete pre‐ and postworkshop case notes and report on subjective changes in knowledge, attitudes, and confidence in assessment and managing suicide risk in older adults. Participants included social workers, nurses, physicians, psychologists, and occupational therapists from a variety of care settings, including outpatient and inpatient medical, outpatient and inpatient mental health, specialty clinics, home, and community. After the workshop, participants demonstrated improvement in the overall quality of case notes (P = .001), greater ability to recognize important conceptual suicide risk categories (P = .003), and reported heightened awareness of the importance of late‐life suicide. The results suggest that educational training may have beneficial effect on the ability of multidisciplinary care providers to identify and manage suicide risk in elderly adults.