bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric Analysis of Medication Errors and Adverse Drug Events Studies
Authors: Huang Hung-Chi , Wang Cheng-Hua , Chen Pi-Ching , Lee Yen-Der
Published: August 2015

Objectives

Medication errors and adverse drug events are a key concern of the health-care industry. The objectives of this study were to map the intellectual structure of the studies of medication errors and adverse drug events and to investigate the developing path of this literature and interrelationships among the main topics.

Methods

The Web of Science database was searched for documentation of medication errors and adverse drug events from 1961 to 2013. The most cited articles and references were profiled and analyzed using HistCite software to draw a historiograph and Ucinet software to draw a sociogram.

Results

The database search revealed 3343 medication errors and 3342 adverse drug event documents. The most cited articles on medication errors focused on 3 key themes from 1961 to 2013, namely, medication errors in adult inpatients, computerized physician order entry in medication error studies, and medication errors in pediatric inpatients. The developing path for the most cited articles about adverse drug events from 1987 to 2013 was as follows: detection, analysis, effect, and prevention from adult inpatient to pediatric inpatient settings and from hospitalized care to ambulatory care. In addition, social network analysis based on the most cited references revealed a close relationship between medication errors and adverse drug events.

Conclusions

The mapping results provide a valuable tool for researchers to access the literature in this field and can be used to help identify the direction of medication errors and adverse drug events research.
Stabilizing the dynamics of laboratory populations ofDrosophila melanogasterthrough upper and lower limiter controls
Authors: Tung Sudipta , Mishra Abhishek , Dey Sutirth
Published: August 2015

Although a large number of methods exist to control the dynamics of populations to a desired state, few of them have been empirically validated. This limits the scope of using these methods in real-life scenarios. To address this issue, we tested the efficacy of two well-known control methods in enhancing different kinds of stability in highly fluctuating, extinction-prone populations ofDrosophila melanogaster. The Upper Limiter Control (ULC) method was able to reduce the fluctuations in population sizes as well as the extinction probability of the populations. On the negative side, it had no effect on the effective population size and required a large amount of effort. On the other hand, Lower Limiter Control (LLC) enhanced effective population size and reduced extinction probability at a relatively low amount of effort. However, its effects on population fluctuations were equivocal. We examined the population size distributions with and without the control methods, to derive biologically intuitive explanations for how these control methods work. We also show that biologically-realistic simulations, using a very general population dynamics model, are able to capture most of the trends of our data. This suggests that our results are likely to be generalizable to a wide range of scenarios.
Inverting proteomics analysis provides powerful insight into the peptide/protein conundrum
Authors: Bin Goh Wilson Wen , Wong Limsoon
Published: August 2015

In proteomics, a large proportion of mass spectrometry (MS) data is ignored due to the lack of, or insufficient statistical evidence for mappable peptides. In reality, only a small fraction of features are expected to be differentially relevant anyway. Mapping spectra to peptides and subsequently, proteins, produces uncertainty at several levels. We propose it is better to analyze proteomic profiling data directly at MS level, and then relate these features to peptides/proteins. In a renal cancer data comprising 12 normal and 12 cancer subjects, we demonstrate that a simple rule-based binning approach can give rise to informative features. We note that the peptides associated with significant spectral bins gave rise to better class separation than the corresponding proteins, suggesting a loss of signal in the peptide-to-protein transition. Additionally, the binning approach sharpens focus on relevant protein splice forms rather than just canonical sequences. Taken together, the inverted raw spectra analysis paradigm, which is realised by the MZ-Bin method described in this article, provides new possibilities and insights, in how MS-data can be interpreted.
Estimating directed connectivity from cortical recordings and reconstructed sources
Authors: Papadopoulou Margarita , Friston Karl , Marinazzo Daniele
Published: August 2015

In cognitive neuroscience, electrical brain activity is most commonly recorded at the scalp. In order to infer the contributions and connectivity of underlying neuronal sources within the brain, it is necessary to reconstruct sensor data at the source level. Several approaches to this reconstruction have been developed, thereby solving the so-called implicit inverse problem (Michel et al. 2004). However, a unifying premise against which to validate these source reconstructions is seldom available. The dataset provided in this work, in which brain activity is simultaneously recorded on the scalp (non-invasively) by electroencephalography (EEG) and on the cortex (invasively) by electrocorticography (ECoG), can be of a great help in this direction. These multimodal recordings were obtained from a macaque monkey under wakefulness and sedation. Our primary goal was to establish the connectivity architecture between two sources of interest (frontal and parietal), and to assess how their coupling changes over the conditions. We chose these sources because previous studies have shown that the connections between them are modified by anaesthesia (Boly et al. 2012). Our secondary goal was to evaluate the consistency of the connectivity results when analyzing sources recorded from invasive data (128 implanted ECoG sources) and source activity reconstructed from scalp recordings (19 EEG sensors) at the same locations as the ECoG sources. We conclude that the directed connectivity in the frequency domain between cortical sources reconstructed from scalp EEG is qualitatively similar to the connectivity inferred directly from cortical recordings, using both data-driven (directed transfer function; DTF) and biologically grounded (dynamic causal modelling; DCM) methods. Furthermore, the connectivity changes identified were consistent with previous findings (Boly et al. 2012). Our findings suggest that inferences about directed connectivity based upon non-invasive electrophysiological data have construct validity in relation to invasive recordings.
INSULIN GROWTH FACTOR I AND ITS RECEPTOR ARE ANTAGONISTIC MODULATORS OF GLUCOSE HANDLING BY ASTROCYTES
Authors: Hernandez-Garzón E. , Fernandez A.M. , Perez-Alvarez A. , Mederos S. , Perez-Domper P. , Bascuñana P. , de la Rosa R.F. , Delgado M. , Pozo M.A. , Miranda-Vizuete A. , Guerrero-Gomez D. , Moreno E. , McCormick P.J. , Santi A. , Genis L. , Trueba A. , Garcia-Caceres C. , Tschöp M.H. , Araque A. , Perea G. , Martin E.D. , Torres Aleman I.
Published: August 2015

Reducing insulin-like growth factor I receptor (IGF-IR) levels or administration of IGF-I show beneficial effects in the brain. We now provide evidence to help resolve this paradox. The unliganded IGF-IR inhibits glucose uptake by astrocytes while its stimulation with IGF-I, in concert with insulin activation of the insulin receptor, produces the opposite effect. In vivo imaging showed that shRNA interference of brain IGF-IR increased glucose uptake by astrocytes while pharmacological blockade of IGF-IR reduced it. Brain18FGlucose-PET of IGF-IR shRNA injected mice confirmed an inhibitory role of unliganded IGF-IR on glucose uptake, whereas glucose-dependent recovery of neuronal activity in brain slices was blunted by pharmacological blockade of IGF-IR. Mechanistically, we found that the unliganded IGF-IR retains glucose transporter 1 (GLUT1), the main glucose transporter in astrocytes, inside the cell while IGF-I, in cooperation with insulin, synergistically stimulates MAPK/PKD to promote association of IGF-IR with GLUT 1 via Rac1/GIPC1 and increases GLUT1 availability at the cell membrane. These findings identify IGF-I and its receptor as antagonistic modulators of brain glucose uptake.
OptoDyCE: Automated System for High-Throughput All-Optical Dynamic Cardiac Electrophysiology
Authors: Klimas Aleksandra , Yu Jinzhu , Ambrosi Christina M. , Williams John C. , Bien Harold , Entcheva Emilia
Published: August 2015

The improvement of preclinical cardiotoxicity testing, the discovery of new ion-channel-targeted drugs, and the phenotyping and use of stem-cell-derived cardiomyocytes and other biologics all necessitate high-throughput (HT), cellular-level electrophysiological interrogation tools. Optical techniques for actuation and sensing provide instant parallelism, enabling contactless dynamic HT testing of cells and small-tissue constructs, not affordable by other means. Here, we consider, computationally and experimentally, the limits of all-optical electrophysiology when applied to drug testing, then implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We validate optical actuation by virally introducing optogenetic drivers in (rat and human) cardiomyocytes or through the modular use of dedicated light-sensitive somatic “spark” cells. We show that this automated all-optical approach provides high-throughput means of cellular interrogation, i.e. allows for dynamic testing of >600 multicellular samples or compounds per hour, and yields high-content information about the action of a drug over time, space and doses.
Comparison of biochemical, histological and morphological response of muscle-based condition indices to varying food levels in pre-flexionDicentrarchus labrax(L.) larvae
Authors: Catalán Ignacio A. , Pilar Olivar M. , Berdalet Elisa
Published: August 2015

The time-response, dynamics, classification power and relationship with survival of three muscle-based condition indices were analysed in pre-flexion sea bass (Dicentrarchus labraxL.) larvae in response to three feeding treatments: fed, non-fed and late-feeding. Larvae were reared at 19 ± 0.8°C and analysed from the second day of feeding (6 days after hatching (DAH)) to just prior the flexion stage (21 DAH). The indices were analysed in trunk muscle at biochemical (RNA/DNA, R/D), histological (percentage of muscle fibre separation, MFS) and morphometric (size-standardised body depth at the anus level, DAZ) level. No index was correlated with muscle length in the fed treatment regardless the period analysed (before or after full external feeding). The R/D was the only index that could detect past feeding differences in larvae ≤ 13 DAH. For larvae > 13 DAH, MFS, R/D andDAZin that order, yielded the best discrimination among treatments. For late-feeding larvae, latency was two days (R/D) and two-four days (MFS). Dynamics of recovery after food addition was also similar for R/D and MFS. Significant relationships between muscle growth and R/D or MFS were only found in larvae > 13 DAH. Both R/D and MFS encompassed the mass mortality event observed in non-fed larvae at 17 DAH. TheDAZlargely failed to give information on the feeding status.
FORGE: multivariate calculation of gene-wide p-values from Genome-Wide Association Studies Authors and Affiliations
Authors: Pedroso Inti Inal , Barnes Michael R , Lourdusamy Anbarasu , Al-Chalabi Ammar , Breen Gerome
Published: August 2015

Genome-wide association studies (GWAS) have proven a valuable tool to explore the genetic basis of many traits. However, many GWAS lack statistical power and the commonly used single-point analysis method needs to be complemented to enhance power and interpretation. Multivariate region or gene-wide association are an alternative, allowing for identification of disease genes in a manner more robust to allelic heterogeneity. Gene-based association also facilitates systems biology analyses by generating a single p-value per gene. We have designed and implemented FORGE, a software suite which implements a range of methods for the combination of p-values for the individual genetic variants within a gene or genomic region. The software can be used with summary statistics (marker ids and p-values) and accepts as input the result file formats of commonly used genetic association software. When applied to a study of Crohn's disease susceptibility, it identified all genes found by single SNP analysis and additional genes identified by large independent meta-analysis. FORGE p-values on gene-set analyses highlighted association with the Jak-STAT and cytokine signalling pathways, both previously associated with CD. We highlight the software's main features, its future development directions and provide a comparison with alternative available software tools. FORGE can be freely accessed at https://github.com/inti/FORGE.
Phylogenetic relationships of the Helmeted Woodpecker (Dryocopus galeatus): A case of interspecific mimicry?
Authors: Benz Brett W. , Robbins Mark B. , Zimmer Kevin J.
Published: August 2015

Examples of phenotypic convergence in plumage coloration have been reported in a wide diversity of avian taxonomic groups, yet the underlying evolutionary mechanisms driving this phenomenon have received little scientific inquiry. Herein, we document a striking new case of plumage convergence in the Helmeted Woodpecker (Dryocopus galeatus) and explore the possibility of visual mimicry among Atlantic Forest woodpeckers. Our multi-locus phylogenetic analyses unequivocally placeD.galeatuswithinCeleus, indicating the former has subsequently converged in appearance upon the distantly related and syntopicDryocopus lineatus, to which it bears a remarkable resemblance in plumage coloration and pattern. Although details of the Helmeted Woodpecker’s ecology and natural history are only now beginning to emerge, its smaller size and submissive behavior are consistent with predictions derived from evolutionary game theory models and the interspecific social dominance mimicry hypothesis (ISDM). Moreover, estimates of avian visual acuity suggest that size-related mimetic deception is plausible at distances ecologically relevant toCeleusandDryocopusforaging behavior. In light of our results, we recommend taxonomic transfer ofD.galeatustoCeleusand emphasize the need for detailed behavioral studies that examine the social costs and benefits of plumage convergence to explicitly test for ISDM and other forms of mimicry in these Atlantic Forest woodpecker communities. Future field studies examining potential cases of competitive mimicry should also take into account the mimic’s acoustic behavior, particularly in the presence of putative model species and other heterospecific competitors, as any discontinuity between morphological and behavioral mimicry would likely preclude the possibility of deception.
Information Processing by Simple Molecular Motifs and Susceptibility to Noise
Authors: McMahon Siobhan , Lenive Oleg , Filippi Sarah , Stumpf Michael P.H.
Published: August 2015

Biological organisms rely on their ability to sense and respond appropriately to their environment. The molecular mechanisms that facilitate these essential processes are however subject to a range of random effects and stochastic processes, which jointly affect the reliability of information transmission between receptors and e.g. the physiological downstream response. Information is mathematically defined in terms of the entropy; and the extent of information flowing across an information channel or signalling system is typically measured by the “mutual information”, or the reduction in the uncertainty about the output once the input signal is known. Here we quantify how extrinsic and intrinsic noise affect the transmission of simple signals along simple motifs of molecular interaction networks. Even for very simple systems the effects of the different sources of variability alone and in combination can give rise to bewildering complexity. In particular extrinsic variability is apt to generate “apparent” information that can in extreme cases mask the actual information that for a single system would flow between the different molecular components making up cellular signalling pathways. We show how this artificial inflation in apparent information arises and how the effects of different types of noise alone and in combination can be understood.
Fast Bayesian Inference of Copy Number Variants using Hidden Markov Models with Wavelet Compression
Authors: Wiedenhoeft John , Brugel Eric , Schliep Alexander
Published: August 2015

By combining Haar wavelets with Bayesian Hidden Markov Models, we improve detection of genomic copy number variants (CNV) in array CGH experiments compared to the state-of-the-art, including standard Gibbs sampling. At the same time, we achieve drastically reduced running times, as the method concentrates computational effort on chromosomal segments which are difficult to call, by dynamically and adaptively recomputing consecutive blocks of observations likely to share a copy number. This makes routine diagnostic use and re-analysis of legacy data collections feasible; to this end, we also propose an effective automatic prior. An open source software implementation of our method is available athttp://bioinformatics.rutgers.edu/Software/HaMMLET/. The web supplement is athttp://bioinformatics.rutgers.edu/Supplements/HaMMLET/.

Author Summary

Identifying large-scale genome deletions and duplications, or copy number variants (CNV), accurately in populations or individual patients is a crucial step in indicating disease factors or diagnosing an individual patient's disease type. Hidden Markov Models (HMM) are a type of statistical model widely used for CNV detection, as well as other biological applications such as the analysis of gene expression time course data or the analysis of discrete-valued DNA and protein sequences.

As with many statistical models, there are two fundamentally different inference approaches. In the frequentist framework, a single estimate of the model parameters would be used as a basis for subsequent inference, making the identification of CNV dependent on the quality of that estimate. This is an acute problem for HMM as methods for finding globally optimal parameters are not known. Alternatively, one can use a Bayesian approach and integrate over all possible parameter choices. While the latter is known to lead to significantly better results, the much—up to hundreds of times—larger computational effort prevents wide adaptation so far.

Our proposed method addresses this by combining Haar wavelets and HMM. We greatly accelerate fully Bayesian HMMs, while simultaneously increasing convergence and thus the accuracy of the Gibbs sampler used for Bayesian computations, leading to substantial improvements over the state-of-the-art.
Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans
Authors: Subasic Deni , Brümmer Anneke , Wu Yibo , Pinto Sérgio Morgado , Imig Jochen , Keller Martin , Jovanovic Marko , Lightfoot Helen Louise , Nasso Sara , Goetze Sandra , Brunner Erich , Hall Jonathan , Aebersold Ruedi , Zavolan Mihaela , Hengartner Michael O.
Published: August 2015

In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA families and the relative contribution of family members to target repression have remained, however, largely unexplored. Here, we used the Caenorhabditis elegans miR-58 miRNA family, composed primarily of the four highly abundant members miR-58.1, miR-80, miR-81, and miR-82, as a model to investigate the redundancy of miRNA family members and their impact on target expression in an in vivo setting. We found that miR-58 family members repress largely overlapping sets of targets in a predominantly additive fashion. Progressive deletions of miR-58 family members lead to cumulative up-regulation of target protein and RNA levels. Phenotypic defects could only be observed in the family quadruple mutant, which also showed the strongest change in target protein levels. Interestingly, although the seed sequences of miR-80 and miR-58.1 differ in a single nucleotide, predicted canonical miR-80 targets were efficiently up-regulated in the mir-58.1 single mutant, indicating functional redundancy of distinct members of this miRNA family. At the aggregate level, target binding leads mainly to mRNA degradation, although we also observed some degree of translational inhibition, particularly in the single miR-58 family mutants. These results provide a framework for understanding how miRNA family members interact to regulate target mRNAs.
Editor and reviewer gender influence the peer review process but not peer review outcomes at an ecology journal
Authors: Fox Charles W. , Burns C. Sean , Meyer Jennifer A.
Published: August 2015

Lack of diversity on editorial boards might generate disparities in editorial and peer review that contribute to gender and geographic disparities in scholarly publishing.

We use a comprehensive data set of the peer review process for all papers submitted to the journal Functional Ecology from January 2004 to June 2014 to examine how gender, seniority and geographic location of editors and reviewers influence reviewer recruitment and scores given to papers by reviewers.

The gender ratio of editors for Functional Ecology was majority male, but the proportion of female editors increased over time. The gender ratio of selected reviewers was also highly majority male, but the proportion of women selected as reviewers increased over the 10 years largely because the number of women on the editorial board increased and female editors invited more female reviewers than did male editors. Male editors selected <25% female reviewers even in the year they selected the most women, but female editors consistently selected ˜30–35% female reviewers. Editors also over‐selected reviewers from their own geographic locality.

Women invited to review were less likely to respond to review invitations, but more likely to accept if they responded. Women invited to review responded to the invitation similarly regardless of whether the editor inviting them was male or female, but men invited to review were both less likely to respond and more likely to decline if the editor was female.

Review scores given to papers did not differ between male and female reviewers, and final decisions (proportion of papers rejected) did not differ between male and female editors.

The proportion of women among selected reviewers decreased with editor seniority when the editor was male but increased with editor seniority when the editor was female. Thus, the gender ratio of selected reviewers differed little between early‐career male and female editors but differed a lot between late‐career (more senior) male and female editors. Individuals invited to review were less likely to agree to review if the editor was more senior.

Editor gender, seniority and geographic location affect who is invited to review for Functional Ecology, and how invitees respond to review invitations, but not the final outcome of the peer review process. To increase diversity of reviewer populations, journals should increase gender, age and geographic diversity of their editorial boards.
Functional assessment of animal interactions with shrub‐facilitation complexes: a formal synthesis and conceptual framework
Authors: Lortie Christopher J. , Filazzola Alessandro , Sotomayor Diego A.
Published: August 2015

Facilitation studies focus primarily on plants often neglecting the extended effects that cascade through ecological networks. Plants interact with other organisms through consumptive effects and a myriad of non‐trophic effects such as habitat amelioration or pollination.

Shrubs are a dominant benefactor species frequent in plant‐facilitation studies but can also have direct and indirect interactions with animals. Herein, we use a systematic review to address the following two objectives: (i) to propose a conceptual framework that explores these interactions including the functional roles of the interacting species, and (ii) to quantitatively summarize the current state of this field examining effects beyond plant–plant interactions.

To date, a relatively limited number of studies have examined the importance of coupled benefactor‐subordinate plant positive interactions with animals (79 studies in total). From this set of studies, 36 studies documented positive plant interactions generating a total of 53 independent instances of either shrub–plant–animal or shrub–animal–plant interactions.

These interaction pathways were evenly split between direct (49%) and indirect (51%) interactions of shrubs with animals. Hypotheses frequently tested included seed trapping, herbivore protection, magnet pollination and facilitation‐mediated secondary seed dispersal. The most common functional role of shrubs was protection from herbivory, and the most common animal role associated with plant‐facilitation complexes was that of a consumer.

None of these studies explored bidirectional plant–animal interactions, used a network approach to describe the interaction sets, nor contrasted interaction strengths. Multitrophic, integrated sets of experiments incorporating plant facilitation into community dynamics are thus critical in advancing management of high‐stress ecosystems wherein positive interactions are commonly reported.
The length‐dependent activation of contraction is equally impaired in impuberal male and female rats in monocrotaline‐induced right ventricular failure
Authors: Lookin Oleg , Balakin Alexander , Kuznetsov Daniil , Protsenko Yuri
Published: August 2015

The length‐dependent activation of contraction is attenuated in the failing myocardium of adult male rats. This pathological change is not seen in adult female rats, possibly because of a protective effect of sex hormones. The present study evaluated length‐dependent changes in isometric twitch, Ca2+ transient (CaT) and action potential (AP) in the right ventricular myocardium of impuberal healthy male and female rats (control) and in rats treated with a single injection of 50 mg/kg monocrotaline (MCT). Compared with sex‐matched control rats, MCT‐treated male and female rats exhibited increased right ventricular weight (134% and 142% of control, respectively), decreased left ventricular weight (72% and 79%), twitch attenuation (48.8 ± 2.7% and 57.5 ± 1.2%) and prolongation (125 ± 3% and 127 ± 2%), CaT attenuation (37.8 ± 0.4% and 39.1 ± 1.1%) and prolongation (114 ± 1% and 116 ± 1%) and AP prolongation at 90% repolarization (195 ± 2% and 203 ± 1%). The MCT‐treated male rats exhibited a 50% lower integral magnitude and an approximately 25% larger time‐to‐peak ‘bump’ compared with control male rats. These parameters in MCT‐treated female rats tended to show similar changes to those seen in the control female rats, with no significant difference between the two groups. In all groups, integral magnitude and time‐to‐peak ‘bump’ increased with length. In conclusion, the length‐dependent activation of contraction was equally blunted in the failing right ventricular myocardium of impuberal male and female rats. This was related to changes in CaT and AP, which were similar between male and female rats. Therefore, puberty is necessary for manifestation of the protective effects of sex hormones on this remodelling.
Asiatic acid alleviates cardiovascular remodelling in rats with L‐NAME‐induced hypertension
Authors: Bunbupha Sarawoot , Prachaney Parichat , Kukongviriyapan Upa , Kukongviriyapan Veerapol , Welbat Jariya Umka , Pakdeechote Poungrat
Published: August 2015

A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME)‐induced hypertensive rats. Male Sprague–Dawley rats were treated with L‐NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF‐α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF‐α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti‐inflammatory and antioxidant activities.
Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats
Authors: Minas Jacqueline N , Thorwald Max A , Conte Debra , Vázquez‐Medina Jose‐Pablo , Nishiyama Akira , Ortiz Rudy M
Published: August 2015

Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II‐dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague–Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II‐induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II‐mediated increase in plasma and heart aldosterone 2.3‐ and 1.8‐fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1‐mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4‐hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress‐associated cardiovascular damage in Ang II‐dependent hypertension.
Parasitic myoma after laparoscopic morcellation: a systematic review of the literature
Authors: Van der Meulen JF , Pijnenborg JMA , Boomsma CM , Verberg MFG , Geomini PMAJ , Bongers MY
Published: August 2015

Background

Laparoscopic morcellation is frequently used for tissue removal after laparoscopic hysterectomy or myomectomy and may result in parasitic myomas, due to seeding of remained tissue fragments in the abdominal cavity. However, little is known about the incidence and risk factors of this phenomenon.

Objectives

To identify the incidence and risk factors for the development of parasitic myoma after laparoscopic morcellation.

Search strategy

A systematic review of the literature in Pubmed (MEDLINE) and Embase was conducted. Reference lists of identified relevant articles were checked for missing case reports.

Selection criteria

Studies reporting on incidence or cases of parasitic myoma diagnosed after laparoscopic morcellation were selected. Studies were excluded when history of laparoscopic morcellation was lacking or final pathology demonstrated a malignancy or endometriosis.

Data collection and analysis

Data were extracted and analysed on incidence of parasitic myomas and characteristics of case reports.

Main results

Fourty‐four studies were included. Sixty‐nine women diagnosed with parasitic myomas after laparoscopic morcellation were identified. Mean age was 40.8 (± 7.5) years (range 24–57), median time between surgery and diagnosis was 48.0 months (range 1–192) and mean number of parasitic myomas was 2.9 (± 3.3) (range 1–16). The overall incidence of parasitic myomas after laparoscopic morcellation was 0.12–0.95%.

Conclusion

Although the incidence is relatively low, it is important to discuss the risk of parasitic myoma after laparoscopic morcellation with women and balance towards alternative treatment options. The duration of steroid exposure after laparoscopic morcellation might be a risk factor for development of parasitic myomas.

Tweetable abstract

Systematic review on the incidence and risk factors for parasitic myoma after laparoscopic morcellation.
Self‐help educational booklets for the prevention of smoking relapse following smoking cessation treatment: a randomized controlled trial
Authors: Maskrey Vivienne , Blyth Annie , Brown Tracey J. , Barton Garry R. , Notley Caitlin , Aveyard Paul , Holland Richard , Bachmann Max O. , Sutton Stephen , Leonardi‐Bee Jo. , Brandon Thomas H. , Song Fujian
Published: August 2015

Aims

Most people who quit smoking for a short term will return to smoking again in 12 months. We tested whether self‐help booklets can reduce relapse in short‐term quitters after receiving behavioural and pharmacological cessation treatment.

Design

A parallel‐arm, pragmatic individually randomized controlled trial.

Setting

Smoking cessation clinics in England. Participants People who stopped smoking for 4 weeks after receiving cessation treatment in stop smoking clinics.

Intervention

Participants in the experimental group (n = 703) were mailed eight booklets, each of which taught readers how to resist urges to smoke. Participants in the control group (n = 704) received a leaflet currently used in practice.

Measurements

The primary outcome was prolonged, carbon monoxide‐verified abstinence from months 4 to 12. The secondary outcomes included 7‐day self#x02010;reported abstinence at 3 and 12 months. Mixed‐effects logistic regression was used to estimate treatment effects and to investigate possible effect modifying variables.

Findings

There were no statistically significant differences between the groups in prolonged abstinence from months 4 to 12 (36.9% versus 38.6%; odds ratio 0.93, 95% confidence interval 0.75–1.16; P = 0.524). In addition, there were no significant differences between the groups in any secondary outcomes. However, people who reported knowing risky situations for relapse and using strategies to handle urges to smoke were less likely to relapse.

Conclusions

In people who stop smoking successfully with behavioural support, a comprehensive self‐help educational programme to teach people skills to identify and respond to high‐risk situations for return to smoking did not reduce relapse.
Sex and age differences in the early identification and treatment of alcohol use: a population‐based study of patients with alcoholic cirrhosis
Authors: Otete Harmony E. , Orton Elizabeth , West Joe , Fleming Kate M.
Published: August 2015

Aim

To estimate sex differences in health‐care utilization among harmful/hazardous drinkers in the period before alcoholic cirrhosis diagnosis, and estimate sex differences in the extent to which alcohol use and brief alcohol interventions were documented for these individuals compared with a control cohort.

Design

Retrospective study using linked general practice and hospital admissions data in England.

Setting

Three hundred and fifty‐seven general practitioner (GP) practices in England.

Participants

A total of 2479 individuals with alcoholic cirrhosis (mean age at diagnosis = 56years), of whom 67% were men; and 24 790 controls without the disease.

Measurements

Rates of primary care visits and hospital admissions prior to the diagnosis of alcoholic cirrhosis for men and women, and the proportion of men and women with alcohol consumption and/or alcohol brief intervention documented in their medical record.

Findings

Compared with the general population, patients with alcoholic cirrhosis used primary and secondary health‐care services more frequently in the years leading up to their diagnosis. In the years prior to diagnosis, men used primary and secondary health‐care services more than did women (P for sex interaction P < 0.0001). Men were more likely than women to have their alcohol use recorded [odds ratio (OR) men = 1.96, 95% confidence interval (CI) = 1.7–2.3; women = 1.63, 95% CI = 1.4–1.8, P for sex interaction P < 0.0017]. By contrast, alcohol interventions were recorded more commonly among women (OR men = 4.3, 95% CI = 3.7–4.9; women = 5.8, 95% CI = 4.7–6.9, P for sex interaction = 0.07), although less common with increasing age (P for age interaction = 0.009).

Conclusions

In the United Kingdom, prior to alcoholic cirrhosis diagnosis, excess health‐care utilization is higher in men than women and men are more likely than women to have their alcohol use recorded. However, women appear to be more likely than men to receive alcohol brief interventions.
Potency trends of Δ9‐tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005–15
Authors: Niesink Raymond J. M. , Rigter Sander , Koeter Maarten W. , Brunt Tibor M.
Published: August 2015

Background and Aims

Between 2000 and 2005 the average percentage of Δ9‐tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly contained any cannabidiol (CBD), a cannabinoid that is thought to offset some of the adverse effects of THC. In 2005, the THC content in Nederwiet was significantly lower than in 2004. This study investigates the further decrease or increase of cannabinoids in these cannabis products.

Methods

From 2005 to 2015 five different cannabis products were bought anonymously in 50 coffeeshops that were selected randomly each year from all coffeeshops in the Netherlands. A total of 2126 cannabis samples were bought, consisting of 664 Nederwiet samples (most popular), 537 Nederwiet samples (supposed strongest varieties), 183 imported herbal cannabis samples, 140 samples of cannabis resin made of Nederwiet and 602 samples of imported cannabis resin. All samples were analysed chemically for their THC, CBD and cannabinol (CBN) content.

Results

Between 2005 and 2015, the mean potencies of the most popular and the strongest Nederwiet and of imported cannabis resin were 16.0 ± 4.0%, 17.0 ± 3,9% and 16.5 ± 6.3%, respectively. Imported herbal cannabis (6.5 ± 3.5%) and cannabis resin made from Nederwiet (30.2 ± 16.4%) contained, respectively, less (β = –10.0, P < 0.001) and more (β = 13.7, P < 0.001) THC than imported cannabis resin. Linear regression models were used to study the trends in THC of the different cannabis products over time. A marginal, but significant (P < 0.001), overall decline of THC per year of 0.22% was found in all cannabis products. However, no significant difference was found between the five products in the THC linear trajectories across time. Of all the cannabis products, only imported cannabis resin contained a relatively high CBD/THC ratio (median 0.42).

Conclusion

The average tetrahydrocannabinol (THC) content of the most popular herbal cannabis products in the Netherlands has decreased slightly since 2005. The popular Nederwiet type still has a relatively high THC to cannabidiol ratio.
Variety of gambling activities from adolescence to age 30 and association with gambling problems: a 15‐year longitudinal study of a general population sample
Authors: Carbonneau Rene , Vitaro Frank , Brendgen Mara , Tremblay Richard E.
Published: August 2015

Aims

To estimate trajectories of gambling variety from mid‐adolescence to age 30 years, and compare the different trajectory groups with regard to the type and the frequency of gambling activities practiced and gambling‐related problems.

Design

Prospective longitudinal cohort study.

Setting

Province of Quebec, Canada.

Participants

A mixed‐gender general population cohort assessed at ages 15 (n = 1882), 22 (n = 1785) and 30 (n = 1358).

Measurements

Adolescent and adult versions of the South Oaks Gambling Screen (SOGS).

Findings

Group‐based trajectory analysis identified three distinct trajectories: a late‐onset low trajectory (26.7% of sample) initiating gambling at age 22, an early‐onset low trajectory (64.8% of sample), characterized by one to two different activities from age 15 onwards and a high trajectory (8.4% of sample), with an average of four to five different activities from age 15 to 30. Males (14.2%) were four times more likely to be on a high trajectory than females (3.5%) (P < 0.001). Preferred types of gambling activities were similar across the three trajectories. Participants on a high trajectory reported higher gambling frequency at ages 15 and 30, and were more likely to experience problem gambling at age 30: 3.09 [95% confidence interval (CI) = 1.66, 5.75] and 2.26 (95% CI = 1.27, 4.04) times more, respectively, than late‐onset low and early‐onset low participants, even when socio‐economic status (SES), frequency of gambling and problem gambling in adolescence, gender, age 30 education, SES and frequency of gambling were controlled.

Conclusions

Engaging in several different types of gambling in early adulthood appears to be a risk factor for emergence of problem gambling.
Risk of mortality on and off methadone substitution treatment in primary care: a national cohort study
Authors: Cousins Gráinne , Boland Fiona , Courtney Brenda , Barry Joseph , Lyons Suzi , Fahey Tom
Published: August 2015

Aim

To assess whether risk of death increases during periods of treatment transition, and investigate the impact of supervised methadone consumption on drug‐related and all‐cause mortality.

Design

National Irish cohort study.

Setting

Primary care.

Participants

A total of 6983 patients on a national methadone treatment register aged 16–65 years between 2004 and 2010.

Measurement

Drug‐related (primary outcome) and all‐cause (secondary outcome) mortality rates and rate ratios for periods on and off treatment; and the impact of regular supervised methadone consumption.

Results

Crude drug‐related mortality rates were 0.24 per 100 person‐years on treatment and 0.39 off treatment, adjusted mortality rate ratio 1.63 [95% confidence interval (CI) = 0.66–4.00]. Crude all‐cause mortality rate per 100 person‐years was 0.51 on treatment versus 1.57 off treatment, adjusted mortality rate ratio 3.64 (95% CI = 2.11–6.30). All‐cause mortality off treatment was 6.36 (95% CI = 2.84–14.22) times higher in the first 2 weeks, 9.12 (95% CI = 3.17–26.28) times higher in weeks 3–4, compared with being 5 weeks or more in treatment. All‐cause mortality was lower in those with regular supervision (crude mortality rate 0.60 versus 0.81 per 100 person‐years) although, after adjustment, insufficient evidence exists to suggest that regular supervision is protective (mortality rate ratio = 1.23, 95% CI = 0.67–2.27).

Conclusions

Among primary care patients undergoing methadone treatment, continuing in methadone treatment is associated with a reduced risk of death. Patients' risk of all‐cause mortality increases following treatment cessation, and is highest in the initial 4‐week period.
Implementation strategies to enhance management of heavy alcohol consumption in primary health care: a meta‐analysis
Authors: Keurhorst Myrna , van de Glind Irene , Bitarello do. Amaral‐Sabadini Michaela , Anderson Peter , Kaner Eileen , Newbury‐Birch Dorothy , Braspenning Jozé , Wensing Michel , Heinen Maud , Laurant Miranda
Published: August 2015

Background and Aims

Screening and brief interventions (SBI) delivered in primary health care (PHC) are cost‐effective in decreasing alcohol consumption; however, they are underused. This study aims to identify implementation strategies that focus on SBI uptake and measure impact on: (1) heavy drinking and (2) delivery of SBI in PHC.

Methods

Meta‐analysis was conducted of controlled trials of SBI implementation strategies in PHC to reduce heavy drinking. Key outcomes included alcohol consumption, screening, brief interventions and costs in PHC. Predictor measures concerned single versus multiple strategies, type of strategy, duration and physician‐only input versus that including mid‐level professionals. Standardized mean differences (SMD) were calculated to indicate the impact of implementation strategies on key outcomes. Effect sizes were aggregated using meta‐regression models.

Results

The 29 included studies were of moderate methodological quality. Strategies had no overall impact on patients’ reported alcohol consumption [SMD = 0.07; 95% confidence interval (CI) =  –0.02 to 0.16], despite improving screening (SMD = 0.53; 95% CI = 0.28–0.78) and brief intervention delivery (SMD = 0.64;95% CI = 0.27–1.02). Multi‐faceted strategies, i.e. professional and/or organizational and/or patient‐orientated strategies, seemed to have strongest effects on patients’ alcohol consumption (P < 0.05, compared with professional‐orientated strategies alone). Regarding SBI delivery, combining professional with patient‐orientated implementation strategies had the highest impact (P < 0.05). Involving other staff besides physicians was beneficial for screening (P < 0.05).

Conclusions

To increase delivery of alcohol screening and brief interventions and decrease patients’ alcohol consumption, implementation strategies should include a combination of patient‐, professional‐ and organizational‐orientated approaches and involve mid‐level health professionals as well as physicians.
Under pressure: adolescent substance users show exaggerated neural processing of aversive interoceptive stimuli
Authors: Berk Lotte , Stewart Jennifer L. , May April C. , Wiers Reinout W. , Davenport Paul W. , Paulus Martin P. , Tapert Susan F.
Published: August 2015

Aims

Adolescents with substance use disorders (SUD) exhibit hyposensitivity to pleasant internally generated (interoceptive) stimuli and hypersensitivity to external rewarding stimuli. It is unclear whether similar patterns exist for aversive interoceptive stimuli. We compared activation in the insular cortex and other brain regions during the anticipation and experience of aversive stimuli between adolescents with SUD and those without.

Design

Cross‐sectional experimental study with two groups.

Participants

Adolescents (ages 15–17 years) with an alcohol or marijuana SUD (n = 18) and healthy comparison subjects (CON, n = 15). Participants were recruited by distributing flyers at local high schools.

Setting

Keck Imaging Center, University of California San Diego, CA, USA.

Measurements

Behavioral and neural responses to a continuous performance task with inspiratory breathing load recorded during an fMRI session. Questionnaires assessed life‐time drug use, anxiety, sensation‐seeking, impulsivity, affect and bodily awareness. Visual analog scales assessed drug craving and breathing load responses.

Findings

Across subjects, experience of breathing load elicited greater bilateral anterior and posterior insula (AI and PI, respectively) activation than anticipation (F(1,31) = 4.16, P < 0.05). SUD exhibited greater left AI and bilateral PI activation during breathing load than anticipation, compared with CON (F(1,31) = 4.16, P < 0.05). In contrast, CON showed greater activation during anticipation than breathing load in left PI, compared with SUD (F(1,31) = 4.16, P < 0.05).

Conclusions

Adolescents with alcohol and marijuana substance use disorders may be hypersensitive to aversive interoceptive stimuli.