bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboxane Inhibitors Attenuate Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administrations
Authors: Nanji Amin A. , Liong Emily C. , Xiao Jia , Tipoe George L.
Published: June 2012

Background

Thromboxane levels are increased in rats fed ethanol (EtOH), whereas thromboxane inhibitors reduce alcoholic liver injury. The aim of this study is to determine whether thromboxane inhibitors could attenuate the already established alcoholic liver injury.

Methods

Rats were fed EtOH and liquid diet for 6 weeks by intragastric infusion to induce liver injury after which EtOH was continued for 2 more weeks, and the rats were treated with either a thromboxane synthase inhibitor (TXSI) or a thromboxane receptor antagonist (TXRA). Liver pathology, lipid peroxidation, nuclear factor‐kappa‐B (NF‐κB) activity, tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and transforming growth factor‐beta1 (TGF‐β1) were evaluated.

Results

Administration of fish oil and EtOH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF‐κB activity, and expression of TNF‐α, COX‐2, and TGF‐β1. Treatment with the thromboxane inhibitors ameliorated a certain level of the pathological and biochemical abnormalities. In particular, TXSI in addition to reducing necrosis, inflammation and fibrosis also decrease the severity of fatty liver.

Conclusions

Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued EtOH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease.
The Over‐Scheduling Hypothesis Revisited: Intensity of Organized Activity Participation During Adolescence and Young Adult Outcomes
Authors: Mahoney Joseph L. , Vest Andrea E.
Published: June 2012

Concern exists that youth who spend a lot of time participating in organized out‐of‐school activities (e.g., sports) are at‐risk for poor developmental outcomes. This concern—called the over‐scheduling hypothesis—has primarily been assessed in terms of adolescent adjustment. This longitudinal study of a nationally representative sample of 1,115 youth (ages 12–18) assessed long‐term relations between intensity of participation during adolescence and adjustment at young adulthood (ages 18–24). Time diaries measured intensity as hours per week of participation. Results showed that, controlling for demographic factors and baseline adjustment, intensity was a significant predictor of positive outcomes (e.g., psychological flourishing, civic engagement, and educational attainment) and unrelated to indicators of problematic adjustment (e.g., psychological distress, substance use, and antisocial behavior) at young adulthood.
A Web‐based approach to blood donor preparation
Authors: France Christopher R. , France Janis L. , Kowalsky Jennifer M. , Copley Diane M. , Lewis Kristin N. , Ellis Gary D. , McGlone Sarah T. , Sinclair Kadian S.
Published: June 2012

BACKGROUND: Written and video approaches to donor education have been shown to enhance donation attitudes and intentions to give blood, particularly when the information provides specific coping suggestions for donation‐related concerns. This study extends this work by comparing Web‐based approaches to donor preparation among donors and nondonors.

STUDY DESIGN AND METHODS: Young adults (62% female; mean [±SD] age, 19.3 [±1.5] years; mean [range] number of prior blood donations, 1.1 [0‐26]; 60% nondonors) were randomly assigned to view 1) a study Web site designed to address common blood donor concerns and suggest specific coping strategies (n = 238), 2) a standard blood center Web site (n = 233), or 3) a control Web site where participants viewed videos of their choice (n = 202). Measures of donation attitude, anxiety, confidence, intention, anticipated regret, and moral norm were completed before and after the intervention.

RESULTS: Among nondonors, the study Web site produced greater changes in donation attitude, confidence, intention, and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for moral norm and anxiety. Among donors, the study Web site produced greater changes in donation confidence and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for donation attitude, anxiety, intention, and moral norm.

CONCLUSION: Web‐based donor preparation materials may provide a cost‐effective way to enhance donation intentions and encourage donation behavior.
Is Measuring Interracial Contact Enough? Racial Concentration, Racial Balance, and Perceptions of Prejudice among Black Americans
Authors: Irizarry Yasmiyn
Published: June 2012

Objectives

Contact theory posits that interracial contact can reduce racial prejudice and perceptions of prejudice. This relationship typically has been looked at from the perspective of whites’ views regarding race and racial relations, but few studies have examined the implications of interracial contact for blacks’ perceptions regarding the extent of prejudice and discrimination.

Methods

With data from the National Survey of Black Workers, I examine whether opportunities for contact in settings with varying racial concentrations in youth and adulthood are associated with blacks’ perceptions of prejudice. I use racial concentration—measured here as mostly black settings, half‐black (racially balanced) settings, and mostly white settings (compared to all‐black settings)—as an indicator of opportunities for interracial contact.

Results

Multivariate analyses offer some evidence of the benefits of opportunities for contact in mixed‐race and mostly white settings for blacks’ perceptions of prejudice.

Conclusion

Although having opportunities for contact can be beneficial, this evidence is limited to noncompetitive childhood environments, namely residential neighborhoods. Findings highlight the important of accounting for the racial balance of settings where interracial contact takes place.
Three‐Dimensional Echocardiographic Features of Unicuspid Aortic Valve Stenosis Correlate with Surgical Findings
Authors: Brantley Hutton P. , Nekkanti Rajasekhar , Anderson Curtis A. , Kypson Alan P.
Published: June 2012

A unicuspid aortic valve (UAV) is a rare congenital defect that may manifest clinically as severe aortic stenosis or regurgitation in the third to fifth decade of life. This report describes two cases of UAV stenosis in adult patients diagnosed by transesophageal echocardiography (TEE). The utility of three‐dimensional TEE in confirming valve morphology and its relevance to transcatheter valve replacement are discussed.
Left Atrial Systolic Force and Outcome in Asymptomatic Mild to Moderate Aortic Stenosis
Authors: Cioffi Giovanni , Cramariuc Dana , Dalsgaard Morten , Davidsen Einar S. , Egstrup Kenneth , Rossebø Anne B. , de Simone Giovanni , Gerdts Eva
Published: June 2012

Background and Aims: In patients with chronic pressure overload due to hypertension or aortic valve stenosis (AS), higher left atrial systolic force (LASF) is associated with a high‐risk cardiovascular (CV) phenotype. We tested LASF as prognostic marker in patients with AS. Methods: We used baseline and outcome data from 1,566 patients recruited in the Simvastatin and Ezetimibe in AS (SEAS) study evaluating the effect of placebo‐controlled simvastatin and ezetimibe treatment on CV events. The primary outcome was a composite of major CV events, including CV death, aortic valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure caused by progression of AS, coronary artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. LASF was calculated by Manning's method. High LASF was defined as >95th percentile (50 Kdynes/cm2) of the distribution within the study population. Results: During 4.3 years of follow‐up, a major CV event occurred in 38 of 78 patients with high LASF (49%) and in 513 of 1,488 (34%) with normal LASF (P = 0.01). In multivariate Cox regression analysis, high LASF predicted higher rate of major CV events (Hazard ratio 1.43 [95% confidence interval 1.01–2.03] independent of aortic valve area and LV mass index. A simple risk score including absence or presence of these three variables allowed risk stratification into low, intermediate, high and very high risk for major CV events during follow‐up (22%, 28%, 38%, and 53%, respectively). Conclusions: Higher LASF provides additional prognostic information in patients with asymptomatic mild‐to‐moderate AS.
Transcatheter Closure of Persistent Ductus Arteriosus in Adults
Authors: BENTHAM JAMES R. , THOMSON JOHN D.R. , GIBBS JOHN L.
Published: June 2012

Objective:
 To describe the technical aspects and outcome of duct occlusion in adults over a 12‐year period.

Methods:
 A single center review of all transcatheter duct closures performed between 2000 and 2012.

Results:
 Of 518 transcatheter duct closures performed, 31 patients were over the age of 16 at the time of procedure (6%). In 10 of the 31 cases, it was not possible to cross the duct from the pulmonary artery. In 4 of those, the duct was small enough to be closed with coils delivered from the aorta (although 1 required a second procedure for a residual shunt). In the remaining 6 cases, it was necessary to cross the duct from the aorta and create an arterio‐venous “circuit” using a snare to deliver an Amplatzer device from the femoral vein. In none of the 487 children who underwent transcatheter duct closure during the same time period was it necessary to deliver the device using an arterio‐venous wire circuit. The increased complexity of the procedure in adults compared with children was further reflected by longer procedure times (median of 37 minutes in adults vs. 24 minutes in children [P < 0.01]) and longer fluoroscopy times (median of 8.4 minutes in adults vs. 4.3 minutes in children [P < 0.025]). There were no major complications.

Conclusions:
 Closure of the arterial duct in adults is safe and effective but ductal anatomy may differ from that seen in childhood, making transcatheter closure technically much more demanding than in children. (J Interven Cardiol 2012;25:501–504)
MC1R variation and melanoma risk in relation to host/clinical and environmental factors in CDKN2A positive and negative melanoma patients
Authors: Ghiorzo Paola , Bonelli Luigina , Pastorino Lorenza , Bruno William , Barile Monica , Andreotti Virginia , Nasti Sabina , Battistuzzi Linda , Grosso Marco , Bianchi‐Scarrà Giovanna , Queirolo Paola
Published: June 2012

Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high‐risk susceptibility genes,
CDKN2A and
CDK4, and variants of the low‐risk gene
MC1R, which is key in the pigmentation process. This case–control study aimed at investigating the influence of the main host and environmental risk factors and of
MC1R variation on CM risk in 390
CDKN2A‐negative and 49
CDKN2A‐positive Italian individuals. Multivariate analysis showed that
MC1R variation, number of nevi and childhood sunburns doubled CM risk in
CDKN2A‐negative individuals. In
CDKN2A‐positive individuals, family history of CM and presence of atypical nevi, rather than
MC1R status, modified risk (20.75‐ and 2.83‐fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both
CDKN2A‐negative and
CDKN2A‐positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria.
Enhanced sonophoretic delivery of 5‐aminolevulinic acid: preliminary human ex vivo permeation data
Authors: Krishnan Gayathri , Grice Jeffrey E. , Roberts Michael S. , Benson Heather A. E. , Prow Tarl W.
Published: June 2012

Background/aims

5‐Aminolevulinate (ALA) is an important photodynamic therapy drug for the treatment of actinic keratoses and other non‐melanoma skin cancers in cosmetically sensitive areas. One limitation of this drug is a relatively high recurrence rate. Our aim was to evaluate the feasibility of ultrasound augmented ALA delivery in excised human skin.

Materials and methods

An ultrasonic delivery device was used to enhance radiolabelled ALA into excised skin. Quantification of ALA was performed after passive and ultrasonic ALA delivery. Transepidermal water loss was used as a measure of barrier function before and after ultrasonic treatment.

Results

We found that ultrasonic treatment dramatically increased the mean cumulative amount of ALA to P< 0.0001 from 4 to 8 h when compared to passive ALA treatment. The flux was calculated to be 54.8 ± 8.0 μg/cm2 h with ultrasound treatment. TEWL increased nearly two‐fold, from 12.3 to 21.0, after ultrasound treatment.

Conclusion

Our study supports the use of ultrasound for improved ALA delivery by showing significant improvements in the cumulative drug load and flux via combined ultrasound and ALA treatment.
THINKING ABOUT THE NATURE AND ROLE OF AUTHORITY IN DEMOCRATIC EDUCATION WITH ROUSSEAU'S EMILE
Authors: Michaud Olivier
Published: June 2012

Educational authority is an issue in contemporary democracies. Surprisingly, little attention has been given to the problem of authority in Jean‐Jacques Rousseau's Emile and his work has not been addressed in the contemporary debate on the issue of authority in democratic education. Olivier Michaud's goals are, first, to address both of these oversights by offering an original reading of the problem of authority in Emile and then to rehabilitate the notion of “educational authority” for democratic educators today. Contrary to progressive readings of Emile, he argues, Rousseau's position on this issue is not reducible to “education against authority.” What appears at first glance to be an education against authority is, in a deeper sense, an education toward and even within authority. Michaud contends that we have to embrace these complexities and contradictions that inform Rousseau's work in order to gain insights into the place and role of authority in democratic education. Michaud sheds light on Rousseau's stance on authority through a close study of specific topics addressed in Emile, including negative education, opinion, one's relation to God, friendship and loving relationships, and, finally, the relation Rousseau established with his reader.
ROUSSEAU AND THE FABLE: RETHINKING THE FABULOUS NATURE OF EDUCATIONAL PHILOSOPHY
Authors: Lewis Tyson E.
Published: June 2012

In this essay Tyson Lewis reevaluates Jean‐Jacques Rousseau's assessment of the pedagogical value of fables in Emile's education using Giorgio Agamben's theory of poetic production and Thomas Keenan's theory of the inherent ambiguity of the fable. From this perspective, the “unreadable” nature of the fable that Rousseau exposed is not simply the result of a child's innocence or developmental immaturity, but is rather a structural quality of the fable as such. Moving from a discussion of Rousseau's description of the fable and its relation to early childhood development, Lewis then telescopes outward into an analysis of Emile as a reenactment of the paradoxes of the fable. While Rousseau critiqued the pedagogical value of the fable, his own pedagogical project is informed by many of the qualities that he attributed to the fable. This return of the fable is enacted through Rousseau's writing on three interconnected levels: the question of the maxim, the paradox of truth, and the paradox of freedom. Lewis argues that if we take seriously the textually fabulous dimension of Emile, then the reader is left exposed to the very same anxieties as a child who is confronted with the ambiguity of the fable. In a concluding gesture, Lewis speculates about what Emile's fabulous dimension means for the practice of educational philosophy itself.
Geographic Variations in Elementary School‐Based Physical Activity Practices*
Authors: Turner Lindsey , Chaloupka Frank J. , Slater Sandy J.
Published: June 2012

BACKGROUND: Physical activity (PA) is associated with health and academic benefits among children, but many schools do not meet national recommendations. This study examined school‐based PA practices in nationally representative samples of public elementary schools, and geographic variations in those practices.

METHODS: Mail‐back surveys were used to gather data from 578 public elementary schools during the 2006‐2007 school year and 680 public elementary schools during the 2009‐2010 school year.

RESULTS: Nationwide, only 1 in 5 schools met the national recommendation of at least 150 minutes of physical education (PE) per week, although PE was more prevalent in the South. Nearly three‐fourths of schools nationwide met recommendations for 20 or more minutes of recess daily, and this was more prevalent in the Midwest but less so in the South. Approximately 40% of schools offered sports and approximately 40% offered other opportunities for PA during the school day. The only practice that increased over time was formal classroom instruction on PA.

CONCLUSIONS: There has been little change in elementary school‐based PA practices nationwide in recent years. With the upcoming renewal of the Elementary and Secondary Education Act, policymakers have an important opportunity to promote increased PA in schools.
Sex Differences in Early Infancy
Authors: Alexander Gerianne M. , Wilcox Teresa
Published: June 2012

Sex‐linked behaviors in infancy have generated a great deal of interest, in part because they offer a way of assessing the extent to which sexually dimorphic behaviors exist before extensive social and educational experiences. This article reviews sex differences in basic and sensory processes, social behavior, and cognitive behavior that have been reported during the 1st year of life, and discusses current knowledge about the underlying basis for these differences and the extent to which they contribute to later behavior. Careful investigation of the interaction between social and biological factors in infancy will be necessary to fully understand the nature and development of human sex differences.
The Effects of Aldosterone Synthase Inhibition on Aldosterone and Cortisol in Patients With Hypertension: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Study
Authors: Andersen Karl , Hartman Daniel , Peppard Thomas , Hermann David , Van Ess Peter , Lefkowitz Martin , Trapani Angelo
Published: June 2012

J Clin Hypertens (Greenwich). 2012; 14:580–587. © 2012 Wiley Periodicals, Inc.

Blockade of the renin‐angiotensin‐aldosterone system (RAAS) is an established method to lower blood pressure in patients with hypertension. Aldosterone, the end product of the RAAS cascade, acts by increasing salt reabsorption in the kidney and catecholamine release from the adrenal medulla. Currently available aldosterone inhibitors have the disadvantage of increasing circulating aldosterone and thus may lead to aldosterone breakthrough. Aldosterone synthase inhibition (ASI) is a novel approach to suppressing the RAAS. Due to homology between the enzymes responsible for aldosterone synthesis (CYP11B2) and cortisol synthesis (CYP11B1), the blockade of aldosterone synthesis may also suppress cortisol release. The authors evaluated the effect of the novel ASI LCI699 on the cortisol response to adrenocorticotropic hormone (ACTH) stimulation in patients with hypertension in order to find the maximally tolerated dose (MTD) in this patient population. Among the 63 patients evaluated, there was a dose‐ and time‐dependent effect of LCI699 on both aldosterone and ACTH‐stimulated cortisol. Based on exposure‐response analysis, the MTD was estimated to be 1.30 mg once daily with a 90% prediction interval of 0.88 mg once daily to 1.81 mg once daily. No patients required intervention for adrenal insufficiency. LCI699 was well tolerated with no serious adverse events.
The Pleiotropic Effects of Phosphodiesterase 5 Inhibitors on Function and Safety in Patients With Cardiovascular Disease and Hypertension
Authors: Chrysant Steven G. , Chrysant George S.
Published: June 2012

J Clin Hypertens (Greenwich). 2012; 14:644–649. © 2012 Wiley Periodicals, Inc.

Phosphodiesterase 5 (PDE‐5) inhibitors are selective blockers of PDE‐5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. cGMP is a potent vasodilator and nitric oxide donor. Since PDE‐5 is widely distributed in the body, it was hypothesized that inhibition of its actions could lead to significant vasodilation, which could benefit patients with coronary artery disease. This hypothesis led to the development of PDE‐5 inhibitors, the first being sildenafil citrate. Studies of sildenafil in patients with coronary artery disease demonstrated a modest cardiovascular effect but a potent action on penile erection in men, resulting in sildenafil becoming first‐line treatment of erectile dysfunction. Two more PDE‐5 inhibitors are now US Food and Drug Administration–approved (vardenafil and tadalafil) for the treatment of erectile dysfunction. Recent studies have demonstrated several beneficial pleiotropic cardiovascular effects of PDE‐5 inhibitors in patients with erectile dysfunction and multiple comorbidities, including coronary artery disease, heart failure, hypertension, and diabetes mellitus. Treatment of these conditions with PDE‐5 inhibitors has been very effective, safe, and well tolerated. Drug interactions have been minimal with the exception of nitrates, where coadministration may result in severe vasodilation and hypotension. These beneficial pleiotropic and safe cardiovascular effects of PDE‐5 inhibitors will be discussed in this concise review.
La dette implicite des plans de pension du secteur public: comparaison internationale
Authors: Ponds Eduard , Severinson Clara , Yermo Juan
Published: June 2012

La plupart des pays disposent de plans de pension distincts pour les employés du secteur public. La charge financière qu'ils représenteront à l'avenir risque de se révéler très lourde car l'Etat est généralement le principal employeur, les promesses de pension du secteur public sont généralement relativement généreuses et les versements seront effectués directement à partir des recettes de l'Etat (système par répartition) ou au titre de plans par capitalisation (fonds de pension) qui sont souvent insuffisamment financés. L'évaluation et les informations communiquées sur les promesses de pension manquent de transparence dans certains pays, qui dissimulent les engagements budgétaires considérables qu'elles font peser sur les travailleurs des générations futures. Afin de pouvoir comparer avec précision la charge financière des plans de pensions publics des différents pays, le présent article propose d'évaluer et de présenter les engagements de retraite non capitalisés selon une approche uniformisée afin d'améliorer la transparence budgétaire et les prises de décision politiques. A partir d'un échantillon de pays membres de l'Organisation de coopération et de développement économiques, le montant des engagements nets non capitalisés à la fin 2008 est estiméà la juste valeur. Les charges budgétaires peuvent également être interprétées comme une dette implicite exprimée à la juste valeur.
Evolution in biocontrol strains: insight from the harlequin ladybird Harmonia axyridis
Authors: Tayeh Ashraf , Estoup Arnaud , Laugier Guillaume , Loiseau Anne , Turgeon Julie , Toepfer Stefan , Facon Benoit
Published: June 2012

After being used as a biocontrol agent against aphids for decades without harmful consequences, the Asian harlequin ladybird Harmonia axyridis has suddenly become an invasive pest on a worldwide scale. We investigate the impact of captive breeding on several traits of this ladybird such as genetic diversity, fecundity, survival and pathogen resistance. We conducted an experiment in the laboratory to compare the fecundity and the susceptibility to the entomopathogenic fungus Beauveria bassiana of wild and biocontrol adults of H. axyridis. We compiled these new findings with already published data. Altogether, our findings suggest that mass rearing of biological control agents may strongly impact genetic diversity and life‐history traits. We discuss how such changes may subsequently affect the fitness of biological control strains in natural environments.
Cataract surgeons outperform medical students in Eyesi virtual reality cataract surgery: evidence for construct validity
Authors: Selvander Madeleine , Åsman Peter
Published: June 2012

Purpose:  To investigate construct validity for modules hydromaneuvers and phaco on the Eyesi surgical simulator.

Methods:  Seven cataract surgeons and 17 medical students performed capsulorhexis, hydromaneuvers, phaco, navigation, forceps, cracking and chopping modules in a standardized manner. Three trials were performed on each module (two on phaco) in the above order. Performance parameters as calculated by the simulator for each trial were saved. Video recordings of the second trial of the modules capsulorhexis, hydromaneuvers and phaco were evaluated with the modified Objective Structured Assessment of Surgical Skill (OSATS) and Objective Structured Assessment of Cataract Surgical Skill (OSACSS) tools.

Results:  Cataract surgeons outperformed medical students with regard to overall score on capsulorhexis (p < 0.001, p = 0.035, p = 0.010 for the tree iterations, respectively), navigation (p = 0.024, p = 0.307, p = 0.007), forceps (p = 0.017, p = 0.03, p = 0.028). Less obvious differences in overall score were found for modules cracking and chopping (p = 0.266, p = 0.022, p = 0.324) and phaco (p = 0.011, p = 0.081 for the two iterations, respectively). No differences in overall score were found on hydromaneuvers (p = 0.588, p = 0.503, p = 0.773), but surgeons received better scores from the evaluations of the modified OSATS (p = 0.001) and OSACSS (capsulorhexis, p = 0.003; hydromaneuvers, p = 0.017; phaco, p = 0.001).

Conclusions:  Construct validity was found on several modules previously not investigated (phaco, hydromaneuvers, cracking and chopping, navigation), and our results confirm previously demonstrated construct validity for capsulorhexis and forceps modules. Interestingly, validation of the hydromaneuvers module required OSACSS video evaluation tool. A further development of the scoring system in the simulator for the hydromaneuvers module would be advantageous and make training and evaluation of progress more accessible and immediate.
A Multi‐Institutional Study Evaluating the Diagnostic Utility of the Spec cPL™and SNAP® cPL™in Clinical Acute Pancreatitis in 84 Dogs
Authors: McCord K. , Morley P.S. , Armstrong J. , Simpson K. , Rishniw M. , Forman M.A. , Biller D. , Parnell N. , Arnell K. , Hill S. , Avgeris S. , Gittelman H. , Moore M. , Hitt M. , Oswald G. , Marks S. , Burney D. , Twedt D.
Published: June 2012

Background

Pancreas‐specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically.

Hypothesis/Objectives

To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic‐specific lipase immunoassays, SpeccPL(SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase.

Animals

A total of 84 dogs; 27 withoutAPand 57 with clinical signs associated withAP.

Methods

Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinicalAPby a consensus of experts blinded toSPECandSNAPresults. Bayesian latent class analyses were used to estimate the diagnostic accuracy ofSPECandSNAP.

Results

The estimates for test sensitivities and specificities, respectively, ranged between 91.5–94.1% and 71.1–77.5% forSNAP, 86.5–93.6% and 66.3–77.0% forSPEC(cutoff value of 200 μg/L), 71.7–77.8% and 80.5–88.0% forSPEC(cutoff value of 400 μg/L), and were 52.4–56.0% and 76.7–80.6% for amylase, and 43.4–53.6% and 89.3–92.5% for lipase.

Conclusions and Clinical Importance

SNAPandSPEChave higher sensitivity for diagnosing clinicalAPthan does measurement of serum amylase or lipase activity. A positiveSPECorSNAPhas a good positive predictive value (PPV) in populations likely to haveAPand a good negative predictive value (NPV) when there is low prevalence of disease.
Correspondence
Authors: Redden R.F.
Published: June 2012

See also response by Ramsey et al
M‐type potassium channels modulate Schaffer collateral–CA1 glutamatergic synaptic transmission
Authors: Sun Jianli , Kapur Jaideep
Published: June 2012

Key points

M‐type potassium channels play a key role in modulating neuronal excitability. However, the effects of M‐channel activation on synaptic transmission are poorly understood.

This study found that an M1 receptor agonist and M‐channel blockers increased action potential‐independent glutamate release at Schaffer collateral–CA1 pyramidal neuron synapses in acute hippocampus slices.

This enhancement was dependent on Ca2+ influx from extracellular space but not intracellular calcium stores.

Inhibition of M‐channels results in the depolarization of CA3 pyramidal neurons and activated presynaptic voltage‐gated P/Q‐ and N‐type calcium channels, which in turn causes Ca2+ influx and increased glutamate release.

Thus, M1 muscarinic agonists modulate action potential‐independent glutamatergic synaptic transmission in the hippocampus by inhibition of presynaptic M‐channels.

Abstract  Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M‐type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M‐type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN‐A‐343, increased the frequency of mEPSCs, but did not alter their amplitude. The M‐channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M‐channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium‐free external medium. Blocking P/Q‐ and N‐type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M‐channels increases presynaptic calcium‐dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M‐channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN‐A‐343 and XE991; these effects were consistent with the closure of M‐channels. Muscarinic activation inhibits M‐channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage‐gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons.
Growth mechanism and surface atomic structure of AgInSe2
Authors: Peña Martin Pamela , Rockett Angus A. , Lyding Joseph
Published: June 2012

The growth of (112)A-oriented AgInSe2 on GaAs (111)A and its surface reconstruction were studied by scanning tunneling microscopy, atomic force microscopy, and other techniques. Films were grown by a sputtering and evaporation method. Topographic STM images reveal that the film grew by atomic incorporation into surface steps resulting from screw dislocations on the surface. The screw dislocation density was ∼1010 cm2. Atomically resolved images also show that the surface atomic arrangement appears to be similar to that of the bulk, with a spacing of 0.35–0.41 nm. There is no observable reconstruction, which is unexpected for a polar semiconductor surface.
Water Resources Management: What Should Be Integrated?
Authors: Hering Janet G. , Ingold Karin M.
Published: June 2012

Appropriately bounded integration can be a basis for sustainable management of water resources.
A Safer Nuclear Enterprise
Authors: Drell Sidney D. , Shultz George P. , Andreasen Steven P.
Published: June 2012

Strong regulation and peer review are needed, particularly in nations new to nuclear power and weapons.
Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria
Authors: Sonnenberg Gregory F. , Monticelli Laurel A. , Alenghat Theresa , Fung Thomas C. , Hutnick Natalie A. , Kunisawa Jun , Shibata Naoko , Grunberg Stephanie , Sinha Rohini , Zahm Adam M. , Tardif Mélanie R. , Sathaliyawala Taheri , Kubota Masaru , Farber Donna L. , Collman Ronald G. , Shaked Abraham , Fouser Lynette A. , Weiner David B. , Tessier Philippe A. , Friedman Joshua R. , Kiyono Hiroshi , Bushman Frederic D. , Chang Kyong-Mi , Artis David
Published: June 2012

Protecting Against a Barrier Breach

In order to coexist peacefully, a “firewall” exists that keeps the commensal bacteria that reside in our intestines and associated lymphoid tissue contained. Several diseases and infections, however, lead to a breach in this barrier, which leads to chronic inflammation and pathology.

Sonnenberg
et al.

(p.
1321
) found that in mice, innate lymphoid cells (ILCs) are critically important for the anatomical containment of commensal bacteria in an interleukin-22 (IL-22)–dependent manner. ILC depletion or blockade of IL-22 led to loss of bacterial containment and systemic inflammation.
The Application of Ecological Theory Toward an Understanding of the Human Microbiome
Authors: Costello Elizabeth K. , Stagaman Keaton , Dethlefsen Les , Bohannan Brendan J. M. , Relman David A.
Published: June 2012

The human-microbial ecosystem plays a variety of important roles in human health and disease. Each person can be viewed as an island-like “patch” of habitat occupied by microbial assemblages formed by the fundamental processes of community ecology: dispersal, local diversification, environmental selection, and ecological drift. Community assembly theory, and metacommunity theory in particular, provides a framework for understanding the ecological dynamics of the human microbiome, such as compositional variability within and between hosts. We explore three core scenarios of human microbiome assembly: development in infants, representing assembly in previously unoccupied habitats; recovery from antibiotics, representing assembly after disturbance; and invasion by pathogens, representing assembly in the context of invasive species. Judicious application of ecological theory may lead to improved strategies for restoring and maintaining the microbiota and the crucial health-associated ecosystem services that it provides.
Honor Thy Gut Symbionts Redux
Authors: Gordon Jeffrey I.
Published: June 2012

Exploring our gut microbial communities with new tools is allowing us to revisit old questions; to develop new concepts about our evolution, postnatal development, systems physiology, individuality, and definitions of health; and to further delineate the impact of our changing life-styles. It is also allowing us to envision exciting new ways for addressing global health problems. This area is inherently interdisciplinary, offering a wealth of opportunities to create new fields, partnerships, and educational initiatives. It is captivating to the public and carries substantial expectations. As such, participating scientists need to sponsor proactive, solution-focused discussions of its societal implications.
Growing Distaste for Nuclear Power Dims Prospects for R&D
Authors: Normile Dennis
Published: June 2012

On 28 May, a Japanese governmental advisory body laid out options for the mix of energy sources in 2030, along with projected effects on the economy and carbon dioxide emissions.
Assessment of HIV-1 Patient Recruitability in the Republic of Guinea-Bissau Using African versus North American Hematology and Biochemistry Reference Intervals
Authors: Gómez Román Victor Raúl , Jensen Sanne Skov , Leo-Hansen Christian , Jensen Kristoffer Jarlov , Janitzek Christoph Mikkel , Rodrigues Candida Medina , Jespersen Sanne , Katzenstein Terese Lea , da Silva Té David , Fomsgaard Anders
Published: June 2012

Hematology and biochemistry reference intervals have been derived from healthy, HIV-negative populations to guide clinical trials worldwide. However, it is less clear how such values may be applied to clinical trials involving HIV-infected individuals. We show that contradictory interpretations about patient recruitability are reached when applying African versus North American reference intervals to an HIV-1 cohort in Guinea-Bissau. These observations underscore the need to question non-African guidelines in the context of HIV intervention clinical trials in Africa.
Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR
34
/L98H Azole Resistance Mechanism
Authors: Camps Simone M. T. , Rijs Antonius J. M. M. , Klaassen Corné H. W. , Meis Jacques F. , O'Gorman Céline M. , Dyer Paul S. , Melchers Willem J. G. , Verweij Paul E.
Published: June 2012

A rapid emergence of azole resistance has been observed in
Aspergillus fumigatus
in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR
34
/L98H mutations in
cyp51A
. This resistance mechanism is now also increasingly being found in other countries. Therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. Studies of 142 European isolates revealed that those with the TR
34
/L98H resistance mechanism showed less genetic variation than azole-susceptible isolates or those with a different genetic basis of resistance and were assigned to only four CSP (putative cell surface protein) types. Sexual crossing experiments demonstrated that TR
34
/L98H isolates could outcross with azole-susceptible isolates of different genetic backgrounds, suggesting that TR
34
/L98H isolates can undergo the sexual cycle in nature. Overall, our findings suggest a common ancestor of the TR
34
/L98H mechanism and subsequent migration of isolates harboring TR
34
/L98H across Europe.
Automated Detection of Toxigenic Clostridium difficile in Clinical Samples: Isothermal
tcdB
Amplification Coupled to Array-Based Detection
Authors: Hicke Brian , Pasko Chris , Groves Benjamin , Ager Edward , Corpuz Maylene , Frech Georges , Munns Denton , Smith Wendy , Warcup Ashley , Denys Gerald , Ledeboer Nathan A. , Lindsey Wes , Owen Charles , Rea Larry , Jenison Robert
Published: June 2012

Clostridium difficile
can carry a genetically variable pathogenicity locus (PaLoc), which encodes clostridial toxins A and B. In hospitals and in the community at large, this organism is increasingly identified as a pathogen. To develop a diagnostic test that combines the strengths of immunoassays (cost) and DNA amplification assays (sensitivity/specificity), we targeted a genetically stable PaLoc region, amplifying
tcdB
sequences and detecting them by hybridization capture. The assay employs a hot-start isothermal method coupled to a multiplexed chip-based readout, creating a manual assay that detects toxigenic
C. difficile
with high sensitivity and specificity within 1 h. Assay automation on an electromechanical instrument produced an analytical sensitivity of 10 CFU (95% probability of detection) of
C. difficile
in fecal samples, along with discrimination against other enteric bacteria. To verify automated assay function, 130 patient samples were tested: 31/32 positive samples (97% sensitive; 95% confidence interval [CI], 82 to 99%) and 98/98 negative samples (100% specific; 95% CI, 95 to 100%) were scored correctly. Large-scale clinical studies are now planned to determine clinical sensitivity and specificity.
Efficient Quantification of HIV-1 in Heparin Plasma Spiked with Cultured HIV-1 by the Roche Cobas TaqMan and Abbott RealTime HIV-1 Tests
Authors: Jagodzinski Linda L. , Weston Holly R. , Liu Ying , O'Connell Robert J. , Peel Sheila A.
Published: June 2012

The current automated real-time HIV-1 viral load assays, the Roche Cobas AmpliPrep/Cobas TaqMan test and the Abbott RealTime test, are FDA cleared for use with EDTA plasma. We show that both real-time reverse transcription-PCR (RT-PCR) tests reliably quantify HIV-1 RNA in heparin plasma specimens spiked with HIV-1 isolate MN.
Prosthetic Valve Endocarditis Caused by a Pasteurella dagmatis-Like Isolate Originating from a Patient's Cat
Authors: Strahm Carol , Goldenberger Daniel , Gutmann Marc , Kuhnert Peter , Graber Peter
Published: June 2012

Pasteurella
species are part of the oral flora of cats and dogs. In humans, they are frequently found in infected animal bite wounds, but invasive infections are rare. This is the first report of prosthetic-valve endocarditis with a
Pasteurella dagmatis
-like species, which originated from the patient's cat.
Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus
Authors: O'Donnell Christopher D. , Wright Amber , Vogel Leatrice N. , Wei Chih-Jen , Nabel Gary J. , Subbarao Kanta
Published: June 2012

Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
Structural Variability of the Herpes Simplex Virus 1 Genome
In Vitro
and
In Vivo
Authors: Mahiet Charlotte , Ergani Ayla , Huot Nicolas , Alende Nicolas , Azough Ahmed , Salvaire Fabrice , Bensimon Aaron , Conseiller Emmanuel , Wain-Hobson Simon , Labetoulle Marc , Barradeau Sébastien
Published: June 2012

Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial-oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation.
In vivo
, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the one
in vitro
was observed, along with a considerable proportion of noncanonical assortment.
Naturally Occurring Swine Influenza A Virus PB1-F2 Phenotypes That Contribute to Superinfection with Gram-Positive Respiratory Pathogens
Authors: Weeks-Gorospe Jenni N. , Hurtig Heather R. , Iverson Amy R. , Schuneman Margaret J. , Webby Richard J. , McCullers Jonathan A. , Huber Victor C.
Published: June 2012

A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of
Streptococcus pneumoniae
superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens:
Streptococcus pneumoniae
,
Staphylococcus aureus
, and
Streptococcus pyogenes
. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with
Streptococcus pyogenes
superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.