bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated CD4
+
CCR5
+
T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques
Authors: Carnathan Diane G. , Wetzel Katherine S. , Yu Joana , Lee S. Thera , Johnson Brent A. , Paiardini Mirko , Yan Jian , Morrow Matthew P. , Sardesai Niranjan Y. , Weiner David B. , Ertl Hildegund C. J. , Silvestri Guido
Published: December 2014

Significance

A major obstacle to developing an effective T-cell–based AIDS vaccine is that the immunization may activate CD4
+
T cells, possibly making them more susceptible to infection by HIV. We tested several vaccine candidates and their effects on mucosal CD4
+
T cells in a simian model of HIV infection [i.e., Simian immunodeficiency virus (SIV) infection of rhesus macaques]. We find that the immunizations did not protect the animals against infection; however, a lower set-point viral load was observed in the vaccinated animals. Importantly, this study showed that the presence of higher levels of activated CD4
+
T cells in mucosal tissues is associated with increased risk of breakthrough SIV infection in vaccinated animals.
Sensory determinants of behavioral dynamics in
Drosophila
thermotaxis
Authors: Klein Mason , Afonso Bruno , Vonner Ashley J. , Hernandez-Nunez Luis , Berck Matthew , Tabone Christopher J. , Kane Elizabeth A. , Pieribone Vincent A. , Nitabach Michael N. , Cardona Albert , Zlatic Marta , Sprecher Simon G. , Gershow Marc , Garrity Paul A. , Samuel Aravinthan D. T.
Published: December 2014

Significance

A previously unidentified set of thermosensory neurons embedded in the olfactory organ of the
Drosophila
larva is shown to be required to drive the animal up temperature gradients toward preferred environments. Optogenetics and optical neurophysiology reveal efficient sensory encoding of both favorable (warming) and unfavorable (cooling) stimuli for distinct components of thermotactic strategy by this one set of neurons. Cooling-evoked activation is used to curtail forward movements in unfavorable directions; warming-evoked deactivation is used to orient new forward movements in favorable directions during turns. Our results pinpoint the locus of thermosensory perception for cool-avoidance behavior in the larva and define how downstream circuits use thermosensory perception to organize navigational behavior.
Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus
Authors: Le Bail Matildé , Martineau Magalie , Sacchi Silvia , Yatsenko Natalia , Radzishevsky Inna , Conrod Sandrine , Ait Ouares Karima , Wolosker Herman , Pollegioni Loredano , Billard Jean-Marie , Mothet Jean-Pierre
Published: December 2014

Significance

NMDA receptors (NMDARs) support patterning and activity of synapses throughout life and are central to many brain disorders. The NMDAR activation requires the concomitant binding of glutamate and a coagonist glycine or
d
-serine. To date, whether a preference for one coagonist at specific connections occurs remains unsolved. Here, we sought to determine when and where
d
-serine and glycine enter into play at hippocampal synapses. We demonstrate that the identity of the NMDAR coagonist is synapse specific and developmentally regulated. Remarkably, this segregation coincides with the subunit composition of postsynaptic NMDARs and the maturation of the tripartite synapse. These results point out the importance of the spatial and temporal switch in coagonist identity for therapeutic interventions aimed at treating deficits in NMDAR activity.
Dialkylresorcinols as bacterial signaling molecules
Authors: Brameyer Sophie , Kresovic Darko , Bode Helge B. , Heermann Ralf
Published: December 2014

Significance

Bacteria can communicate with each other by small diffusible molecules, a process termed quorum sensing. Many bacteria use acylated homoserine lactones (AHLs) as signals, which are sensed by so-called LuxR-type receptors. With the photopyrones from the insect pathogenic bacterium
Photorhabdus luminescens
, we recently identified the first quorum sensing molecules different from AHLs that are sensed by a LuxR-type receptor. Here we describe the second novel quorum sensing molecule sensed by a LuxR-type receptor of
Photorhabdus
species, PauR of the human pathogen
Photorhabdus asymbiotica
. We demonstrate that
P. asymbiotica
communicates via dialkylresorcinols (DARs) and cyclohexanediones (CHDs). As the synthesis pathway is widespread, and often present in human pathogens, we discuss DARs and CHDs as novel and widespread signaling molecules.
β-Helical architecture of cytoskeletal bactofilin filaments revealed by solid-state NMR
Authors: Vasa Suresh , Lin Lin , Shi Chaowei , Habenstein Birgit , Riedel Dietmar , Kühn Juliane , Thanbichler Martin , Lange Adam
Published: December 2014

Significance

Bactofilins are a new class of cytoskeletal proteins that are involved in key cellular processes. For instance, in the human pathogen
Helicobacter pylori
, they are responsible for maintaining its characteristic helical cell shape, a feature required for cells to efficiently colonize the gastric mucus. So far the atomic structure of bactofilin filaments has remained elusive, as the large bactofilin assemblies are not amenable to standard methods for 3D structure determination. Here, we have applied a combination of solid-state NMR and electron microscopy and discovered that bactofilins adopt a β-helical architecture, which has not been observed before for other cytoskeletal filaments. Interestingly, however, the structure bears similarities to that of the fungal prion protein HET-s.
G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons
Authors: Connelly Timothy , Yu Yiqun , Grosmaitre Xavier , Wang Jue , Santarelli Lindsey C. , Savigner Agnes , Qiao Xin , Wang Zhenshan , Storm Daniel R. , Ma Minghong
Published: December 2014

Significance

Mechanical stimuli (pressure, shear stress, membrane stretch, etc.) are a basic form of stimulation that can induce physiological responses in many body organs (skin, muscle, ear, lung, airway, kidney, blood vessels, etc.). The current dogma in sensory systems is that mechanical stimuli are mainly transduced by force-gated ion channels. Our study reveals a previously unidentified cascade for mechanotransduction in neurons and suggests that G protein-coupled receptors may have an overlooked function as mechanical sensors. This finding establishes a molecular mechanism through which the nose sends an afferent signal of breathing to the brain to facilitate integration of orofacial sensation and synchronize delta/theta-band activity in certain brain regions with respiration.
Parasitism alters three power laws of scaling in a metazoan community: Taylor’s law, density-mass allometry, and variance-mass allometry
Authors: Lagrue Clément , Poulin Robert , Cohen Joel E.
Published: December 2014

Significance

Power laws of scaling are major achievements of ecology. Such empirical laws say that one quantity varies as some power of another quantity. For example, Taylor’s law says that the variance of population density changes as a power of the mean population density. Density-mass allometry says that the mean population density is a power-law function of the mean body mass. We show, to our knowledge for the first time in any animal community, that the variance of population density is a power-law function of mean body mass, and that the parameters of all three power laws just mentioned are influenced by whether the animals are parasites, free-living parasitized species, or free-living unparasitized species. Lifestyle matters in ecology.
Intracellular osteopontin regulates homeostasis and function of natural killer cells
Authors: Leavenworth Jianmei W. , Verbinnen Bert , Wang Qin , Shen Erxia , Cantor Harvey
Published: December 2014

Significance

Maintenance of a pool of natural killer (NK) cells with optimal immune function is crucial for host defense against pathogens or cancerous tumor formation. Here we identify intracellular osteopontin (OPN-i) as an essential molecular component responsible for maintenance of functional NK cell expansion. Absence of OPN-i results in failure to maintain normal NK cellularity and increased cell death following stimulation by cytokine interleukin-15. OPN-deficient NK cells fail to successfully navigate the contraction phase of the immune response, resulting in impaired expansion of long-lived NK cells and defective responses to viral infection and tumor cells. Insight into the contribution of OPN-i to NK cell responses may provide the basis for improved approaches to immunotherapy for infectious disease and cancer.
Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval
Authors: de Carvalho Myskiw Jociane , Furini Cristiane Regina Guerino , Schmidt Bianca , Ferreira Flávia , Izquierdo Ivan
Published: December 2014

Significance

Blockade of the retrieval of contextual fear conditioning by intrahippocampal muscimol administration does not impede extinction of the task measured up to 1 wk later, its eventual spontaneous recovery at 14 d, or its inhibition by two different protein synthesis inhibitors given into the hippocampus. These results show that extinction and retrieval are separate processes and strongly suggest that extinction is triggered or gated by the conditioned stimulus even in the absence of retrieval.
Examining Potential Substance use Disorders among Former Interscholastic Athletes
Authors: Veliz Philip , McCabe Sean Esteban
Published: December 2014

Background

Despite numerous studies examining the association between competitive sports participation and substance use behaviors among adolescents and young adults, the use of standardized measures to assess potential substance use disorders has been largely neglected. The objective of this study was to examine if past involvement in interscholastic sports (competitive school-sponsored sports) was associated with potential substance use disorders in young adulthood.

Methods

Data for this study were taken from the Student Life Survey (SLS). A total of 3442 young adults participated in the SLS during the spring semester in 2013, with 74% of males and 71% of females indicating participation in interscholastic sport during high school.

Results

Respondents who participated in interscholastic sports during high school had higher odds of positive screens for potential alcohol use disorders when compared with their peers who did not participate in interscholastic sports. No association was detected between interscholastic sports participation and potential drug abuse disorders. Moreover, previous involvement in certain types of sports was found to be associated with positive screens for potential alcohol use disorders (i.e., crew and football) and positive screens for potential drug abuse disorders (i.e., lacrosse) among the sample of young adults.

Conclusions

School and community sport organizations should be aware of the potential link between sports participation and potential substance use disorders, and may consider brief substance use screeners during yearly physicals to monitor potential substance use problems among athletes.
Motivational Interviewing with and without Normative Feedback for Adolescents with Substance Use Problems: A Preliminary Study
Authors: Smith Douglas C. , Ureche Daniel J. , Davis Jordan P. , Walters Scott T.
Published: December 2014

Background

Many adolescents in need of substance use disorder treatments never engage in treatment. Further, the most promising interventions that could be adapted to target treatment engagement often use normative feedback (NF) despite concerns about its appropriateness for adolescents. This preliminary study will inform a larger trial designed to isolate whether NF is an inert, helpful, or harmful active ingredient within pretreatment motivational interviewing (MI) interventions designed to increase treatment engagement.

Methods

Adolescents ( N = 48) presenting for treatment intake assessments were randomized to receive MI ( n = 22) or MI+NF ( n = 26) immediately following their assessments. Three-month outcomes included the percentage of youth engaged in treatment, the percentage of youth reporting past-month binge drinking, and the percentage of days of abstinence.

Results

Treatments were delivered with high fidelity, and a high proportion of eligible participants were recruited and retained in this study. Participants significantly increased their percentage of days of abstinence by approximately 10% at follow-up ( d = .32, P =.03), with no significant differences between groups. Fifty-five percent of youth in MI and 41.7% of youth in MI+NF engaged in treatment (odds ratio [OR] = .60, nonsignificant; 95% confidence interval, CI [0.136–2.68]).

Conclusions

Larger trials should test whether NF is an active ingredient in adolescent MI interventions, and should also determine the mechanisms through which MI+NF may produce effects.
PRSice: Polygenic Risk Score software
Authors: Euesden Jack , Lewis Cathryn M. , O’Reilly Paul F.
Published: December 2014

Summary: A polygenic risk score (PRS) is a sum of trait-associated alleles across many genetic loci, typically weighted by effect sizes estimated from a genome-wide association study. The application of PRS has grown in recent years as their utility for detecting shared genetic aetiology among traits has become appreciated; PRS can also be used to establish the presence of a genetic signal in underpowered studies, to infer the genetic architecture of a trait, for screening in clinical trials, and can act as a biomarker for a phenotype. Here we present the first dedicated PRS software, PRSice (‘precise'), for calculating, applying, evaluating and plotting the results of PRS. PRSice can calculate PRS at a large number of thresholds (“high resolution”) to provide the best-fit PRS, as well as provide results calculated at broad P-value thresholds, can thin Single Nucleotide Polymorphisms (SNPs) according to linkage disequilibrium and P-value or use all SNPs, handles genotyped and imputed data, can calculate and incorporate ancestry-informative variables, and can apply PRS across multiple traits in a single run. We exemplify the use of PRSice via application to data on schizophrenia, major depressive disorder and smoking, illustrate the importance of identifying the best-fit PRS and estimate a P-value significance threshold for high-resolution PRS studies.

Availability and implementation: PRSice is written in R, including wrappers for bash data management scripts and PLINK-1.9 to minimize computational time. PRSice runs as a command-line program with a variety of user-options, and is freely available for download from http://PRSice.info

Contact:  jack.euesden@kcl.ac.uk or paul.oreilly@kcl.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
The neural correlates of dreaming
Authors: Siclari F. , Baird B. , Perogamvros L. , Bernardi G. , LaRocque J. , Riedner B. , Boly M. , Postle B. , Tononi G.
Published: December 2014

Consciousness never fades during wake. However, if awakened from sleep, sometimes we report dreams and sometimes no experiences. Traditionally, dreaming has been identified with REM sleep, characterized by a wake-like, globally ‘activated’, high-frequency EEG. However, dreaming also occurs in NREM sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep. Using high-density EEG, we contrasted the presence and absence of dreaming within NREM and REM sleep. In both NREM and REM sleep, the presence of dreaming was associated with a local decrease in low-frequency activity in posterior cortical regions. High-frequency activity within these regions correlated with specific dream contents. Monitoring this posterior ‘hot zone’ predicted the presence/absence of dreaming during NREM sleep in real time, suggesting that it may constitute a core correlate of conscious experiences in sleep.
Practice of Cardiac Auscultation: Clinical perspectives and its implications on computer aided diagnosis
Authors: Mandal Subhamoy , Martis Roshan J , Mandana K M , Rajendra Acharya U , Chatterjee Jyotirmoy , Mahadevappa Manjunatha , Ray Ajoy K
Published: December 2014

Study of the disease demographics in human population indicates that cardiac ailments are the primary cause of premature death, and a need for emergent technologies is felt to address the rising trend. However, development of automated heart sound analysis system and its usage at the grassroot levels for cardiac pre-screening have been hindered by the lack proper understanding of the intrinsic characteristics of cardiac auscultation. In this article we present an investigatory report based on a nationwide survey conducted on the practice of cardiac auscultation for determination of its effectiveness in diagnosis. The aims are to achieve better validation of heart sound acquisition methods and use the clinical feedback from cardiologists for improvements in the classification of the cardiac abnormalities. Results obtained from six different classifiers used in the study are illustrated, which show a remarkable specificity using an improvised classification hierarchy, derived based on clinical recommendations. The study addresses the needs for better understanding of the relevancy of heart sound signal parameters, recording transducers, recording location and the inherent complexity associated in interpretation of heart sounds, specially in noisy environments of out-patient departments and primary healthcare centers. Further, the inter-relationship between heart sound and other advance medical imaging modalities, and the need for more focused training in cardiac auscultation among the medical and paramedical staff is investigated.
Soybean miR172c Targets the Repressive AP2 Transcription Factor NNC1 to Activate ENOD40 Expression and Regulate Nodule Initiation
Authors: Wang Youning , Wang Lixiang , Zou Yanmin , Chen Liang , Cai Zhaoming , Zhang Senlei , Zhao Fang , Tian Yinping , Jiang Qiong , Ferguson Brett J. , Gresshoff Peter M. , Li Xia
Published: December 2014

MicroRNAs are noncoding RNAs that act as master regulators to modulate various biological processes by posttranscriptionally repressing their target genes. Repression of their target mRNA(s) can modulate signaling cascades and subsequent cellular events. Recently, a role for miR172 in soybean (Glycine max) nodulation has been described; however, the molecular mechanism through which miR172 acts to regulate nodulation has yet to be explored. Here, we demonstrate that soybean miR172c modulates both rhizobium infection and nodule organogenesis. miR172c was induced in soybean roots inoculated with either compatible Bradyrhizobium japonicum or lipooligosaccharide Nod factor and was highly upregulated during nodule development. Reduced activity and overexpression of miR172c caused dramatic changes in nodule initiation and nodule number. We show that soybean miR172c regulates nodule formation by repressing its target gene, Nodule Number Control1, which encodes a protein that directly targets the promoter of the early nodulin gene, ENOD40. Interestingly, transcriptional levels of miR172c were regulated by both Nod Factor Receptor1α/5α-mediated activation and by autoregulation of nodulation-mediated inhibition. Thus, we established a direct link between miR172c and the Nod factor signaling pathway in addition to adding a new layer to the precise nodulation regulation mechanism of soybean.
Nonword repetition errors of children with and without specific language impairments (SLI)
Authors: Burke Heidi L. , Coady Jeffry A.
Published: December 2014

Background

Two ubiquitous findings from the literature are that (1) children with specific language impairments (SLI) repeat nonwords less accurately than peers with typical language development (TLD), and (2) all children repeat nonwords with frequent phonotactic patterns more accurately than low‐probability nonwords. Many studies have examined repetition accuracy, but little work has examined children's errors.

Aims

To examine nonword repetition errors from a previously published study in terms of phonotactic probability.

Methods & Procedures

Eighteen children with SLI (mean age = 9;2) and 18 age‐matched controls (mean age = 8;11) repeated three‐ and four‐syllable nonwords. Substitutions were analysed in terms of phoneme frequency and phonotactic probability of the syllable containing the substitution.

Outcomes & Results

Results for all children show that phoneme substitutions generally involved replacement with more frequently occurring phonemes. Also, the resulting phonotactic probability within syllables containing substitutions was greater than the probability of the targets. This trend did not differ by group.

Conclusions & Implications

These results suggest that both children with SLI and children with TLD substitute less frequent phonemes with more frequent ones, and less probabilistic syllables with higher probability ones.
Early language impairments and developmental pathways of emotional problems across childhood
Authors: Goh Kok Yew Shaun , O'Kearney Richard
Published: December 2014

Background

Language impairments are associated with an increased likelihood of emotional difficulties later in childhood or adolescence, but little is known about the impact of LI on the growth of emotional problems.

Aims

To examine the link between early language status (language impaired (LI), typical language (TL)) and the pattern and predictors of growth in emotional difficulties from school entry to the start of high school in a large cohort of Australian children.

Methods & Procedures

Unconditional latent growth curves of emotional difficulties were modelled across four waves (ages 4–5, 6–7, 8–9 and 10–11) using data from 1627 boys (280 LI, 1347 TL) and 1609 girls (159 LI, 1450 TL). Conditional latent growth curves estimated the main effects of LI on the severity and slope of growth in emotional problems. Simultaneous multiple regression tested the interaction between language status and the other predictors of the development of emotional symptoms.

Outcomes & Results

LI predicted a significant persistent elevation in severity of emotional difficulties across childhood among boys (d = 0.33–0.57) and girls (d = 0.25–0.39) but was not associated with their growth. LI moderated the association between hostile parenting and the severity of emotional symptoms for boys and the effect of socioeconomic status (SES) and temperamental sociability on the linear and quadratic growth of emotional problems for girls but had no impact on the influence of other predictors.

Conclusions & Implications

There is no effect of LI on the characteristic rate and shape of growth in emotional symptoms across childhood although LI children maintain elevated severities of emotional difficulties. The associations between child reactivity, peer problems, prosocial behaviours, maternal distress and parental warmth and the development of emotional difficulties were the same for LI and TL children. LI enhanced the influence of hostile parenting on a higher severity of emotional symptoms for boys and of lower SES on a faster rate of development of emotional symptoms for girls. LI offset the usual protective effect of higher sociability and the usual vulnerability of higher social avoidance to a faster increase in emotional symptoms with age.
Changing policy and legislation and its effects on inclusive and special education: a perspective fromEngland
Authors: Norwich Brahm
Published: December 2014

This article, by Brahm Norwich of the Graduate School of Education, University of Exeter, sets the recent legislative changes in the special education system in England, the Children and Families Act (2014), in the context of wider changes in the school system, such as changes in curriculum–assessment, the governance of schools and inspection arrangements. It also sets out the recent legislative changes in terms of the recent history of the Labour period of government, with its adoption of market principles with social inclusion as key policy commitments. A case study of a secondary school is presented to illustrate some of these points. Despite the new legislative system being described as a radical approach involving aspiration and support for special educational needs, the article argues that proposed changes promise to be marginal and defined by policy commitments to markets and small government. Moreover, there are continuing and unresolved issues from the Labour Government period that are still to be fully addressed. Research is also presented on the distribution of pupils with Statements in secondary schools and the recent rising pattern of special school placement for the first time in 30 years.
Association of eNOS gene polymorphisms and systemic lupus erythematosus in southeast Iran
Authors: Sandoughi Mahnaz , Salimi Saeedeh , Zakeri Zahra , Darbandi Ebrahim Jahani , Jahantigh Mehdi , Moudi Bita
Published: December 2014

Background and objectives

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown etiology. Genetic and environmental factors play important roles in the pathogenesis of SLE. The primary objective of this study was to investigate the possible association of eNOS gene intron 4b/a, Glu298Asp and T‐786C polymorphisms with SLE in southeast Iran populations.

Patients and methods

This was a case‐control study comparing eNOS polymorphisms in 106 SLE patients and 196 age‐ and sex‐matched healthy controls. The 4b/a, Glu298Asp and T‐786C polymorphisms were analyzed using polymerase chain reaction and restriction fragment length polymorphism.

Results

Our findings indicated that the 4b/a polymorphism was associated with SLE, and the risk of SLE was 3.5‐ and 1.75‐fold higher in patients with aa and ba genotypes than in patients with bb genotype. No association was observed between Glu298Asp and T‐786C polymorphisms and SLE. There were no differences in eNOS gene polymorphisms between the Balouch and Fars population.

Conclusion

Statistically significant differences were observed in genotypes and allele frequencies of 4b/a polymorphism between patients with SLE and healthy controls in southeast Iran.
A casemix study of patients seen by a dermatology trainee in rural and urban outpatient settings
Authors: Tilakaratne Dev , Warren Lachlan , Menz Jennifer
Published: December 2014

Background/Objectives

For 8 years South Australian dermatologists have provided an outreach service to the Northern Territory (NT), including rural and remote areas. In 2012 and 2013, a trainee accompanied a dermatologist on these outreach visits. This is the first prospective study that documents the spectrum of dermatological diseases requiring outpatient specialist input in various settings in the NT, and also the first study to compare the clinical experience of one Australian dermatology trainee in urban and rural settings.

Materials and Methods

Characteristics of patients managed primarily by the outreach dermatology registrar were recorded prospectively from February 2013 to July 2013. The data from the trainee's urban encounters were compared to that of the rural centres. The spectrum of conditions seen in these two settings was placed in the disease categories specified in the Australasian College of Dermatologists (ACD) curriculum.

Results

The Royal Adelaide Hospital outpatient experience provided greater exposure to skin neoplasms, lymphoproliferative and myeloproliferative disorders and non‐infectious neutrophilic/eosinophilic disorders. The outreach sites provided greater exposure to infections, adnexal diseases and genodermatoses. Both urban and rural experiences provided a broad exposure to the disease categories outlined in the ACD curriculum.

Conclusions

The spectrum of disease requiring specialist dermatology input varies between urban South Australia and rural NT. The inclusion of dermatology trainees in outreach visits broadens their clinical exposure. It is recommended that other dermatology service providers in Australia consider documenting clinical casemix comparisons to assess dermatology demand, outcomes and trainee exposure.
Priming Predispositions and Changing Policy Positions: An Account of When Mass Opinion Is Primed or Changed
Authors: Tesler Michael
Published: December 2014

Prior research provides limited insights into when political communications prime or change citizens’ underlying opinions. This article helps fill that void by putting forth an account of priming and opinion change. I argue that crystallized attitudes should often be primed by new information. An influx of attention to less crystallized preferences, however, should lead individuals to alter their underlying opinions in accordance with prior beliefs. Since predispositions acquired early in the life cycle—such as partisanship, religiosity, basic values, and group‐based affect/antagonisms—are more crystallized than mass opinion about public policy, media and campaign content will tend to prime citizens’ predispositions and change their policy positions. Both my review of previous priming research and original analyses presented in this study from five new cases strongly support the crystallization‐based account of when mass opinion is primed or changed. I conclude with a discussion of the article's potential political, methodological, and normative implications.
Analgesic effect of ultrasound‐guided transversus abdominis plane block after total abdominal hysterectomy: a randomized, double‐blind, placebo‐controlled trial
Authors: Røjskjær Jesper O. , Gade Erik , Kiel Louise B. , Lind Morten N. , Pedersen Lars M. , Kristensen Billy B. , Rasmussen Yvonne H. , Foss Nicolai B.
Published: December 2014

Objective

To assess the effect of bilateral ultrasound‐guided transversus abdominis plane block with ropivacaine compared with placebo as part of a multimodal analgesic regimen.

Design

A randomized, double‐blind, placebo‐controlled trial following the CONSORT criteria.

Setting

Hvidovre University Hospital.

Patients

Forty‐six women scheduled for total abdominal hysterectomy.

Intervention

Women received either ropivacaine 0.75%, 20 mL (n = 24) or 0.9% saline, 20 mL (n = 24) in the transversus abdominis plane on each side.

Main outcome measures

Primary outcome was the 24‐h postoperative morphine consumption. Secondary outcomes were pain scores at rest and during coughing, postoperative nausea and vomiting at 1, 2, 4, 6, 8, and 24 h, and time to first mobilization.

Results

There was no difference in the mean 24‐h postoperative morphine consumption between the two groups (p = 0.733). The ropivacaine group had significantly lower median pain scores at 1 h (p = 0.008) and 2 h (p = 0.027) postoperatively at rest and at 8 h (p = 0.028) during coughing. There was no significant difference in other secondary outcomes.

Conclusion

There was no reduction in 24‐h morphine consumption when using an ultrasound‐guided transversus abdominis plane block in women undergoing total abdominal hysterectomy. As part of a multimodal regimen the transversus abdominis plane block showed some effect on pain scores at rest only in the early postoperative period.
Identification and characterization of genes, encoding the 3‐hydroxybutyrate dehydrogenase and a putative lipase, in an avirulent spontaneous Legionella pneumophila serogroup 6 mutant
Authors: Scaturro Maria , Barello Cristina , Giusti Melania De , Fontana Stefano , Pinci Federica , Giuffrida Maria Gabriella , Ricci Maria Luisa
Published: December 2014

Legionella pneumophila is a pathogen widespread in aquatic environment, able to multiply both within amoebae and human macrophages. The aim of this study was to identify genes differently expressed in a spontaneous avirulent Legionella pneumophila serogroup 6 mutant, named Vir−, respect the parental strain (Vir+), and to determine their role in the loss of virulence. Protein profiles revealed some differences in Vir− proteomic maps, and among the identified proteins the undetectable 3‐hydroxybutyrate dehydrogenase (BdhA) and a down‐produced lipase. Both Legionella enzymes were studied before and were here further characterized at genetic level. A significant down‐regulation of both genes was observed in Vir− at the transcriptional level, but the use of defined mutants demonstrated that they did not affect the intracellular multiplication. A mutant (MS1) showed an accumulation of poly‐3‐hydroxybutyrate (PHB) granules suggesting a role of bdhA gene in its degradation process. The lipase deduced amino acid sequence revealed a catalytic triad, typical of the ‘lipase box’ characteristic of PHB de‐polymerase enzymes, that let us suppose a possible involvement of lipase in the PHB granule degradation process. Our results revealed unexpected alterations in secondary metabolic pathways possibly linking the loss of virulence to Legionella lack of energy sources.
Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?
Authors: Lindahl Kim Hein , Sørensen Flemming Brandt , Jonstrup Søren Peter , Olsen Karen Ege , Loeschke Siegfried
Published: December 2014

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.
Indications of newer and older anti‐epileptic drug use: findings from a southern Italian general practice setting from 2005–2011
Authors: Italiano Domenico , Capuano Annalisa , Alibrandi Angela , Ferrara Rosarita , Cannata Angelo , Trifirò Gianluca , Sultana Janet , Ferrajolo Carmen , Tari Michele , Tari Daniele Ugo , Perrotta Margherita , Pagliaro Claudia , Rafaniello Concita , Spina Edoardo , Arcoraci Vincenzo
Published: December 2014

Aims

The aim of the study was to analyze the prescribing pattern of both newer and older AEDs.

Methods

A population of almost 150 000 individuals registered with 123 general practitioners was included in this study. Patients who received at least one AED prescription over 2005–2011 were identified. The 1 year prevalence and cumulative incidence of AED use, by drug class and individual drug, were calculated over the study period. Potential predictors of starting therapy with newer AEDs were also investigated.

Results

The prevalence of use per 1000 inhabitants of older AEDs increased from 10.7 (95% CI10.1, 11.2) in 2005 to 13.0 (95% CI12.4, 13.6) in 2011, while the incidence remained stable. Newer AED incidence decreased from 9.4 (95% CI 8.9, 9.9) in 2005 to 7.0 (95% CI 6.6, 7.5) in 2011, with a peak of 15.5 (95% CI 14.8, 16.1) in 2006. Phenobarbital and valproic acid were the most commonly prescribed AEDs as starting therapy for epilepsy. Gabapentin and pregabalin accounted for most new pain‐related prescriptions, while valproic acid and lamotrigine were increasingly used for mood disorders. Female gender (OR 1.36, 95% CI 1.20, 1.53), age ranging between 45–54 years (OR 1.39, 95% CI 1.16, 1.66) and pain as an indication (OR 16.7, 95% CI, 13.1, 21.2) were associated with newer AEDs starting therapy.

Conclusions

Older AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin.
The sedimentary and tectonic evolution of the Amur River and North Sakhalin Basin: new evidence from seismic stratigraphy and Neogene–Recent sediment budgets
Authors: Nicholson Uisdean , van der Es Bas , Clift Peter D. , Flecker Rachel , Macdonald David I. M.
Published: December 2014

The North Sakhalin Basin in the western Sea of Okhotsk has been the main site of sedimentation from the Amur River since the Early Miocene. In this article, we present regional seismic reflection data and a Neogene–Recent sediment budget to constrain the evolution of the basin and its sedimentary fill, and consider the implications for sediment flux from the Amur River, in particular testing models of continental‐scale Neogene drainage capture. The Amur‐derived basin‐fill history can be divided into five distinct stages: the first Amur‐derived sediments (>21–16.5 Ma) were deposited during a period of transtension along the Sakhalin‐Hokkaido Shear Zone, with moderately high sediment flux to the basin (71 Mt year−1). The second stage sequence (16.5–10.4 Ma) was deposited following the cessation of transtension, and was characterised by a significant reduction in sediment flux (24 Mt year−1) and widespread retrogradation of deltaic sediments. The third (10.4–5.3 Ma) and fourth (5.3–2.5 Ma) stages were characterised by progradation of deltaic sediments and an associated increase in sediment flux (48–60 Mt year−1) to the basin. Significant uplift associated with regional transpression started during this time in southeastern Sakhalin, but the north‐eastward propagating strain did not reach the NE shelf of Sakhalin until the Pleistocene (<2.5 Ma). This uplift event, still ongoing today, resulted in recycling of older deltaic sediments from the island of Sakhalin, and contributed to a substantially increased total sediment flux to the adjacent basinal areas (165 Mt year−1). Adjusted rates to discount these local erosional products (117 Mt year−1) imply an Amur catchment‐wide increase in denudation rates during the Late Pliocene–Pleistocene; however, this was likely a result of global climatic and eustatic effects, combined with tectonic processes within the Amur catchment and possibly a smaller drainage capture event by the Sungari tributary, rather than continental‐scale drainage capture involving the entire upper Amur catchment.
Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation
Authors: Nakaguro Masato , Kiyonari Shinichi , Kishida Satoshi , Cao Dongliang , Murakami‐Tonami Yuko , Ichikawa Hitoshi , Takeuchi Ichiro , Nakamura Shigeo , Kadomatsu Kenji
Published: December 2014

Neuroblastoma (NB) is a childhood malignant tumor that arises from precursor cells of the sympathetic nervous system. Spontaneous regression is a phenomenon unique to NBs and is caused by differentiation of tumor cells. PES1 is a multifunctional protein with roles in both neural development and ribosome biogenesis. Various kinds of models have revealed the significance of PES1 in neurodevelopment. However, the roles of PES1 in NB tumorigenesis and differentiation have remained unknown. Here we show that NB cases with MYCN amplification and clinically unfavorable stage (INSS stage 4) express higher levels of PES1. High PES1 expression was associated with worse overall and relapse‐free survival. In NB cell lines, PES1 knockdown suppressed tumor cell growth and induced apoptosis. This growth inhibition was associated with the expression of NB differentiation markers. However, when the differentiation of NB cell lines was induced by the use of all‐trans retinoic acid, there was a corresponding decrease in PES1 expression. Pes1 expression of tumorspheres originated from MYCN transgenic mice also diminished after the induction of differentiation with growth factors. We also reanalyzed the distribution of PES1 in the nucleolus. PES1 was localized in the dense fibrillar component, but not in the granular component of nucleoli. After treatment with the DNA‐damaging agent camptothecin, this distribution was dramatically changed to diffuse nucleoplasmic. These data suggest that PES1 is a marker of NB outcome, that it regulates NB cell proliferation, and is associated with NB differentiation.
Survival from uveal melanoma in Western Australia 1981–2005
Authors: Chew Avenell L , Spilsbury Katrina , Isaacs Timothy W
Published: December 2014

Background

The survival rates for patients diagnosed with uveal melanoma in Australia are unknown. Few long‐term studies of uveal melanoma are available, and it is unclear whether their results are applicable to the Australian population.

Design

Retrospective population‐based study.

Participants

Patients diagnosed with uveal melanoma between 1981 and 2005 in Western Australia.

Methods

Three hundred eight cases were included. Relative survival and Cox regression were performed. Variables tested for their predictive ability included patient age and sex, tumour‐specific variables, and treatment modality.

Main Outcome Measures

All‐cause survival rates and relative survival rates of patients with diagnosed uveal melanoma.

Results

Relative survival rates for the entire cohort were 88.2%, 81.4% and 71.4% at 3, 5 and 10 years, respectively. Predictors of worse survival included mixed‐cell tumour morphology (hazard ratio [HR] = 2.1; P‐value = 0.002), tumour location at the ciliary body (HR = 1.7; P‐value = 0.029) and tumour apical height more than 5 mm (HR 1.9, P‐value = 0.026). Of all patients who underwent enucleation, those diagnosed in 1998–2005 died twice as fast (HR = 2.3; P‐value = 0.004). In the 17 patients with metastasis, the median survival time from date of diagnosis of metastasis was 3.1 months.

Conclusions

These survival estimates are comparable to those reported for the USA, and more optimistic than those reported for most European‐based studies. Tumour apical height, tumour site, tumour morphology and having an enucleation in certain calendar periods of diagnosis were independent predictors of survival. Survival prognosis for patients with diagnosed metastatic uveal melanoma is very poor.
Relationship between pharmacokinetics and pharmacodynamics of calcineurin inhibitors in renal transplant patients
Authors: Albring Antje , Wendt Laura , Harz Nino , Engler Harald , Wilde Benjamin , Kribben Andreas , Lindemann Monika , Schedlowski Manfred , Witzke Oliver
Published: December 2014

The calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus (Tac) are immunosuppressive drugs, which are typically employed in the field of organ transplantation. Both drugs have narrow therapeutic indices, highly variable pharmacokinetics, and are associated with severe adverse effects. In current clinical routine, the dose finding of CNIs is based on the measurement of their blood concentrations. However, this method is limited in its ability to determine the biological impact of the drug. Alternative monitoring strategies, focusing on the pharmacodynamics of CNIs, could help to personalize drug dosing and optimize the treatment with CNIs. Therefore, we analyzed the relationship between pharmacokinetic and pharmacodynamic of the CNIs CsA (n = 9) and Tac (n = 8) in stable renal transplant patients during a 12‐h dosing period. We observed a significant decrease in the drug–blood concentration during the course of the day and in parallel a significant recovery of T cell function. In addition, our data document that analysis of intracellular interleukin (IL)‐2 production and determination of the IL‐2 release are accurate parameters for monitoring the pharmacodynamics of CNIs.
Liver transplantation arrests and reverses muscle wasting
Authors: Bergerson Joseph T. , Lee Jun‐Goo , Furlan Alessandro , Sourianarayanane Achuthan , Fetzer David T. , Tevar Amit D. , Landsittel Douglas P. , DiMartini Andrea F. , Dunn Michael A.
Published: December 2014

Muscle wasting, sarcopenia, is common in advanced cirrhosis and predicts adverse outcomes while awaiting and following liver transplantation. Frequent post‐transplant worsening of sarcopenia has attracted recent interest. It is unknown whether this serious problem is an expected metabolic consequence of transplantation or results from confounding conditions such as recurrent allograft liver disease or avoidable post‐transplant complications. To clarify this question, we studied pre‐ and post‐transplant muscle mass in a retrospective cohort of 40 patients transplanted for three diseases – alcoholic cirrhosis, non‐alcoholic steatohepatitis cirrhosis, and primary sclerosing cholangitis cirrhosis – in whom allograft disease recurrence was monitored and excluded, and who lacked common post‐transplant muscle wasting complications such as sepsis, renal failure, ischemia, and cholestasis. We measured skeletal muscle index (SMI) using computed tomography before and 12–48 months after transplant. SMI as a categorical variable significantly improved, from 18 patients above the normal cutoff pre‐transplant to 28 post‐transplant (p = 0.008). SMI increases were greatest in patients with the lowest pre‐transplant SMI (p < 0.01). As a continuous variable, mean SMI remained stable, with a non‐significant trend toward improvement. We conclude that after liver transplantation sarcopenia does not progress but is arrested and frequently improves in the absence of confounding conditions.
Development of a new attract‐and‐kill technology for Oriental fruit moth control using insecticide‐impregnated fabric
Authors: Huang Juan , Gut Larry J. , Grieshop Matthew
Published: December 2014

The potential of a novel attract‐and‐kill pouch for pest control was assessed in a series of behavioral studies examining its effect on male Oriental fruit moth (OFM), Grapholita molesta (Busck) (Lepidoptera: Tortricidae). In contrast to traditional attract‐and‐kill technologies that combine insecticides and pheromones in a paste or gel, the prototype device consisted of a fabric pouch that was impregnated with deltamethrin and baited with a separate sex pheromone lure placed inside the pouch. This new approach not only provided a large insecticide‐treated surface for males to interact with but also prevented males from directly contacting the attractant, so as to minimize the risk of moths overloading their sensory system with sex pheromones. In a forced‐contact bioassay, increasing dosages of deltamethrin in the fabric from 0.02 to 0.6 mg cm−2 increased mortality or knockdown rate of OFM 2, 4, and 24 h after 5 s exposure. Likewise, duration of exposure to a deltamethrin‐treated pouch significantly affected the knockdown rate of OFM. All of the exposed moths were knocked down after 60 s exposure. In a flight tunnel bioassay, OFM males exhibited similar behaviors when offered either a control or deltamethrin‐treated pouch, indicating no repellency of the toxicant. Among the moths that contacted treated pockets, 98% was either knocked down or dead 1 h after exposure. Attract‐and‐kill pouches aged in the field for nearly a year resulted in a similar rate of knockdown of OFM compared to fresh pouches. Surprisingly, addition of a UV blocker, 2,4‐dihydroxybenzophenone, did not influence efficacy of deltamethrin in aged pouches. This simple, highly selective, and long‐lasting attract‐and‐kill device may provide an alternative control for OFM.