bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Association of Poor Sleep Quality With Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer
Authors: Jung Dooyoung , Lee Kwang-Min , Kim Won-Hyoung , Lee Joo-Young , Kim Tae-Yong , Im Seock-Ah , Lee Kyung-Hun , Spiegel David , Hahm Bong-Jin
Published: July 2016

Objective

Risk factors for chemotherapy-induced nausea and vomiting (CINV) include older age, female sex, alcohol consumption, and a history of motion sickness. Although gastrointestinal symptoms are found to be related with sleep and mood in other conditions, little is known about their effects on CINV.

Methods

This prospective observational study recruited patients with early-stage breast cancer who had recovered from surgery before receiving a first cycle of anthracycline and cyclophosphamide–based chemotherapy. Candidate factors associated with CINV were assessed before chemotherapy by using the following: the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, the Epworth Sleepiness Scale, and the Hospital Anxiety and Depression Scale. Chemotherapy-induced nausea (CIN) and chemotherapy-induced vomiting (CIV) were defined according to a numeric rating scale (0–10) as follows: ≥3, nausea; ≥1, vomiting.

Results

Between February 2012 and May 2014, data were collected from 198 patients. Chemotherapy-induced nausea occurred in 35.4% of patients, and CIV occurred in 31.3%. Chemotherapy-induced nausea was significantly associated with poor sleep quality (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.13–5.46; p = 0.024) and pretreatment nausea (OR, 4.81; 95% CI, 1.84–12.62; p = 0.001). Likewise, CIV was significantly associated with poor sleep quality (OR, 2.64; 95% CI, 1.21–5.78; p = 0.015) and pretreatment nausea (OR, 3.07; 95% CI, 1.23–7.66; p = 0.016).

Conclusions

Poor sleep quality increases risk of CINV in patients with breast cancer. Sleep problems should be assessed and considered in the management of CINV.
Observing Electroconvulsive Therapy Changes Students’ Attitudes
Authors: Pranjkovic Tamara , Degmecic Dunja , Medic Flajsman Ana , Gazdag Gábor , Ungvari Gabor S. , Kuzman Martina Rojnic
Published: July 2016

Aim

To assess the impact of education and direct observation of electroconvulsive therapy (ECT) on medical students' attitudes toward ECT in particular and psychiatric treatment in general in Croatia.

Method

Two self-administered questionnaires were completed by year 4 medical students twice, at the beginning and the end of the psychiatry clerkship. Students were divided into 2 groups: those who observed an ECT session (47.9%) and those who did not (52.1%).

Results

The survey was completed by 190 students yielding a response rate of 79.8%. Students' attitudes toward ECT and other methods of psychiatric treatment and psychiatry in general changed in positive direction after the clerkship in both groups. However, the attitudes toward ECT of students who observed a live ECT session became more positive than those who did not. Likewise, students who observed ECT were more likely to agree to receive ECT and had better knowledge about ECT compared with the other group.

Conclusions

Having watched a live ECT session had a positive effect on students' attitudes toward ECT and other types of psychiatric treatment. Watching live ECT sessions should be mandatory during the psychiatric clerkship.
Response to Electroconvulsive Therapy in Patients With Autism Spectrum Disorder and Intractable Challenging Behaviors Associated With Symptoms of Catatonia
Authors: Sajith Sreedharan Geetha , Liew Siew Fai , Tor Phern Chern
Published: July 2016

Background

There are several reports of electroconvulsive therapy (ECT) used in autism spectrum disorder (ASD) in the context of catatonic symptoms. We describe response to ECT in two adults with ASD and intellectual disability with intractable aggression and self-injurious behaviors associated with catatonic symptoms who had not responded to standard interventions.

Method

Unilateral ECT at a frequency of 3 times a week was given followed by weekly maintenance ECT.

Results

Patients' catatonic symptoms included episodes of agitation and echophenomena. Electroconvulsive therapy resulted in significant improvement in their behavior problems but 1 patient relapsed when the ECT was discontinued or frequency of treatment reduced. The second patient required 2 courses of ECT before improvement which was maintained on weekly ECT.

Conclusions

Electroconvulsive therapy could be a potentially beneficial intervention in patients with ASD and severe challenging behaviors associated with catatonic symptoms including agitated or excited forms of catatonia.
Electroconvulsive Therapy and All-Cause Mortality in Texas, 1998–2013
Authors: Dennis Nora M. , Dennis Paul A. , Shafer Alan , Weiner Richard D. , Husain Mustafa M.
Published: July 2016

Introduction

Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Since 1995, Texas has maintained an ECT database including patient diagnoses and outcomes, and reporting any deaths within 14 days of receiving an ECT treatment, encompassing a total of 166,711 ECT treatments administered in Texas over the previously unreported period of 1998 to 2013.

Methods

Descriptive analysis summarized information on deaths reported during the 16-year period—cause of death, type of treatment (index or maintenance) and patient demographics. Multiple logistic regression of death incidence by treatment session was performed to determine whether patient age, sex, race, diagnosis, or year of treatment was associated with death after ECT.

Results

Of those deaths occurring within 1 day of an ECT treatment, the death rate was 2.4 per 100,000 treatments. Looking at all deaths within 14 days of an ECT treatment, the death rate increased to 18 per 100,000 treatments but included all deaths regardless of likelihood of causal association with ECT, for example, accidents and suicides, the latter a leading cause of death among individuals with severe major depression or other disorders for which ECT is indicated. Death rate increased significantly with increasing patient age (P = 0.001) and male sex (P = 0.009), and there was a nonsignificant trend toward increased death amongst patients with bipolar disorder or schizophrenia (P = 0.058) versus depression.

Conclusions

Our data indicate that ECT is in general a safe procedure with respect to the likelihood of immediate death. Suicide remains a significant risk in ECT patients, despite evidence that ECT reduces suicidal ideation.
Single cell transcriptomics, mega-phylogeny and the genetic basis of morphological innovations in Rhizaria
Authors: Krabberød Anders K. , Orr Russell J. S. , Bråte Jon , Kristensen Tom , Bjørklund Kjell R. , Shalchian-Tabrizi Kamran
Published: July 2016

The innovation of the eukaryote cytoskeleton enabled phagocytosis, intracellular transport and cytokinesis, and is responsible for diverse eukaryotic morphologies. Still, the relationship between phenotypic innovations in the cytoskeleton and their underlying genotype is poorly understood. To explore the genetic mechanism of morphological evolution of the eukaryotic cytoskeleton we provide the first single cell transcriptomes from uncultivable, free-living unicellular eukaryotes: the radiolarian speciesLithomelissa setosaandSticholonche zanclea. Analysis of the genetic components of the cytoskeleton and mapping of the evolution of these to a revised phylogeny of Rhizaria reveals lineage-specific gene duplications and neo-functionalization of α and β tubulin in Retaria, actin in Retaria and Endomyxa, and Arp2/3 complex genes in Chlorarachniophyta. We show how genetic innovations have shaped cytoskeletal structures in Rhizaria, and how single cell transcriptomics can be applied for resolving deep phylogenies and studying gene evolution of uncultivable protist species.
The Influence of Canalization on the Robustness of Boolean Networks
Authors: Kadelka C. , Kuipers J. , Laubenbacher R.
Published: July 2016

Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed byk-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept toc-sensitivity and provides formulas for the activities andc-sensitivity of generalk-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of thec-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally efficient way to obtain Derrida values of Boolean networks, deterministic or stochastic, that does not involve simulation.
Neural signatures of value comparison in human cingulate cortex during decisions requiring an effort-reward trade-off
Authors: Klein-Flügge Miriam C , Kennerley Steven W , Friston Karl , Bestmann Sven
Published: July 2016

Integrating costs and benefits is crucial for optimal decision-making. While much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human functional magnetic resonance imaging during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area (SMA) and the caudal portion of dorsal anterior cingulate cortex (dACC) encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modelled effort-discounted subjective values using a novel behavioural model. This revealed that the same network of regions involving dACC and SMA encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in SMA and ventro-medial PFC (vmPFC) correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not vmPFC as typically reported for outcome-based choice. Furthermore, distinct frontal circuits ‘drive’ behaviour towards reward-maximization and effort-minimization.

Significance Statement

The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behaviour, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioural characterization of how humans trade-off reward-maximization with effort-minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits ‘drive’ behaviour towards reward-maximization or effort-minimization.
Influence of rotational nucleosome positioning on transcription start site selection in animals promoters
Authors: Dreos René , Ambrosini Giovanna , Bucher Philipp
Published: July 2016

The recruitment of RNA-Pol-II to the transcription start site (TSS) is an important step in gene regulation in all organisms. Core promoter elements (CPE) are conserved sequence motifs that guide Pol-II to the TSS by interacting with specific transcription factors (TFs). However, only a minority of animal promoters contains CPEs. It is still unknown how Pol-II selects the TSS in their absence. Here we present a comparative analysis of promoters’ sequence composition and chromatin architecture in five eukaryotic model organisms, which shows the presence of common and unique DNA-encoded features used to organize chromatin. Analysis of Pol-II initiation patterns uncovers that, in the absence of certain CPEs, there is a strong correlation between the spread of initiation and the intensity of the 10 bp periodic signal in the nearest downstream nucleosome. Moreover, promoters’ primary and secondary initiation sites show a characteristic 10 bp periodicity in the absence of CPEs. We also show that DNA natural variants in the region immediately downstream the TSS are able to affect both the nucleosome-DNA affinity and Pol-II initiation pattern. These findings support the notion that, in addition to CPEs mediated selection, sequence-induced nucleosome positioning could be a common and conserved mechanismof TSS selection in animals.

Author Summary

Gene transcription is a complex process that starts with the recruitment and positioning of Pol-II enzyme at the transcription start site (TSS). Specific promoter sequences, known as core promoter elements (CPEs) facilitate this process. Surprisingly, only a fraction of promoters contain them. It is still unknown how Pol-II choses the start site in their absence. Arecently proposed alternative mechanism implicates positioned nucleosomes in the TSS selection. Here, we provide new evidence of the existence of such mechanism with a comparative analysis of promoter’s features across the animal kingdom. We analysed the promoter’s DNA sequence composition in 5 organisms and found conserved and unique consensus sequencesused to organize chromatin in the region of the first nucleosome downstream the TSS (N+1). Moreover, we found that all organisms show a strong correlation between the spread of Pol-II initiation and the strength of the DNA-encoded signal in the N+1 region. A detailed analysis of Pol-II initiation sites reveals also the presence of a 10 bp periodicity that is correlated with the intensity of the DNA signal in the N+1 region. Importantly, we report that genetic variants that alter the DNA-nucleosome affinity in that region alter Pol-II initiation spread as well.
Accelerating computational Bayesian inference for stochastic biochemical reaction network models using multilevel Monte Carlo sampling
Authors: Warne David J. , Baker Ruth E. , Simpson Matthew J.
Published: July 2016

Investigating the behavior of stochastic models of biochemical reactionnetworks generally relies upon numerical stochastic simulation methods to generate many realizations of the model. For many practical applications, such numerical simulation can be computationally expensive. The statistical inference of reaction rate parameters based on observed data is, however, a significantly greater computational challenge; often relying upon likelihood-free methods such as approximate Bayesian computation, that requirethe generation of millions of individual stochastic realizations. In this study, we investigate a new approach to computational inference, based on multilevel Monte Carlo sampling: we approximate the posterior cumulative distribution function through a combination of model samples taken over a range of acceptance thresholds. We demonstrate this approach using a variety of discrete-state, continuous-time Markov models of biochemical reactionnetworks. Results show that a computational gain over standard rejection schemes of up to an order of magnitude is achievable without significant loss in estimator accuracy.

Author Summary

We develop a new method to infer the reaction rate parameters for stochastic models of biochemical reaction networks. Standard computational approaches, based on numerical simulations, are often used to estimate parameters. These computational approaches, however, are extremely expensive, potentially requiring millions of simulations. To alleviate this issue, we apply a different method of sampling allowing us to find an optimal trade-off between performance and accuracy. Our approach is approximately one order of magnitude faster than standard methods, without significant loss in accuracy.
Commentary: Is the Statistic Value All We Should Care about in Neuroimaging?
Authors: Chen Gang , Taylor Paul A. , Cox Robert W.
Published: July 2016

Here we address an important issue that has been embedded within the neuroimaging community for a long time: the absence of effect estimates in results reporting in the literature. The statistic value itself, as a dimensionless measure, does not provide information on the biophysical interpretation of a study, and it certainly does not represent the whole picture of a study. Unfortunately, in contrast to standard practice in most scientific fields, effect (or amplitude) estimates are usually not provided in most results reporting in the current neuroimaging publications and presentations. Possible reasons underlying this general trend include: 1) lack of general awareness, 2) software limitations, 3) inaccurate estimation of the BOLD response, and 4) poor modeling due to our relatively limited understanding of FMRI signal components. However, as we discuss here, such reporting damages the reliability and interpretability of the scientific findings themselves, and there is in fact no overwhelming reason for such a practice to persist. In order to promote meaningful interpretation, cross validation, reproducibility, meta and power analyses in neuroimaging, we strongly suggest that, as part of good scientific practice, effect estimates should be reported together with their corresponding statistic values. We provide several easily adaptable recommendations for facilitating this process.
Acute nicotine enhances spontaneous recovery of contextual fear and changes c-fos early gene expression in infralimbic cortex, hippocampus, and amygdala
Authors: Kutlu Munir G. , Tumolo Jessica M. , Holliday Erica , Garrett Brendan , Gould Thomas J.
Published: July 2016

Exposure therapy, which focuses on extinguishing fear-triggering cues and contexts, is widely used to treat post-traumatic stress disorder (PTSD). Yet, PTSD patients who received successful exposure therapy are vulnerable to relapse of fear response after a period of time, a phenomenon known as spontaneous recovery (SR). Increasing evidence suggests ventral hippocampus, basolateral amygdala, and infralimbic cortex may be involved in SR. PTSD patients also show high rates of comorbidity with nicotine dependence. While the comorbidity between smoking and PTSD might suggest nicotine may alter SR, the effects of nicotine on SR of contextual fear are unknown. In the present study, we tested the effects of acute nicotine administration on SR of extinguished contextual fear memories and c-fos immediate early gene immunohistochemistry in mice. Our results demonstrated that acute nicotine enhanced SR of extinguished fear whereas acute nicotine did not affect retrieval of unextinguished contextual memories. This suggests that the effect of acute nicotine on SR is specific for memories that have undergone extinction treatment. C-fos immunoreactive (IR) cells in the ventral hippocampus and basolateral amygdala were increased in the nicotine-treated mice following testing for SR, whereas the number of IR cells in the infralimbic cortex was decreased in the same group. Overall, this study suggests that nicotine may adversely affect context-specific relapse of fear memories and this effect is potentially mediated by the suppression of cortical regions and increased activity in the ventral hippocampus and amygdala.
Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice
Authors: Liu Yan , Sun Jiandong , Wang Yubin , Lopez Dulce , Tran Jennifer , Bi Xiaoning , Baudry Michel
Published: July 2016

Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation- (TBS) induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression impairs hippocampus-dependent learning. We previously showed that TBS-induced LTP was associated with calpain-1 mediated truncation of PHLPP1.To better understand the roles of these 2 genes in synaptic plasticity and learning and memory, we generated a double knockout (DKO) mouse by crossing the parent strains. Surprisingly, DKO mice exhibit normal TBS-induced LTP, and the learning impairments in fear conditioning and novel object or novel location recognition were absent in the DKO mice. Moreover, TBS-induced ERK activation in field CA1 of hippocampal slices, which is impaired in both single deletion mice, was restored in the DKO mice. These results further strengthen the roles of both CANP1 and PHLPP1 in synaptic plasticity and learning and memory, and illustrate the complexities of the interactions between multiple pathways participating in synaptic plasticity.
Using crystal structure prediction to rationalize the hydration propensities of substituted adamantane hydrochloride salts
Authors: Mohamed Sharmarke , Karothu Durga Prasad , Naumov Panče
Published: July 2016

The crystal energy landscapes of the salts of two rigid pharmaceutically active molecules reveal that the experimental structure of amantadine hydrochloride is the most stable structure with the majority of low-energy structures adopting a chain hydrogen-bond motif and packings that do not have solvent accessible voids. By contrast, memantine hydrochloride which differs in the substitution of two methyl groups on the adamantane ring has a crystal energy landscape where all structures within 10 kJ mol−1of the global minimum have solvent-accessible voids ranging from 3 to 14% of the unit-cell volume including the lattice energy minimum that was calculated after removing water from the hydrated memantine hydrochloride salt structure. The success in using crystal structure prediction (CSP) to rationalize the different hydration propensities of these substituted adamantane hydrochloride salts allowed us to extend the model to predict under blind test conditions the experimental crystal structures of the previously uncharacterized 1-(methylamino)adamantane base and its corresponding hydrochloride salt. Although the crystal structure of 1-(methylamino)adamantane was correctly predicted as the second ranked structure on the static lattice energy landscape, the crystallization of aZ′ = 3 structure of 1-(methylamino)adamantane hydrochloride reveals the limits of applying CSP when the contents of the crystallographic asymmetric unit are unknown.
Transferable force field for crystal structure predictions, investigation of performance and exploration of different rescoring strategies using DFT-D methods
Authors: Broo Anders , Nilsson Lill Sten O.
Published: July 2016

A new force field, here called AZ-FF, aimed at being used for crystal structure predictions, has been developed. The force field is transferable to a new type of chemistry without additional training or modifications. This makes the force field very useful in the prediction of crystal structures of new drug molecules since the time-consuming step of developing a new force field for each new molecule is circumvented. The accuracy of the force field was tested on a set of 40 drug-like molecules and found to be very good where observed crystal structures are found at the top of the ranked list of tentative crystal structures. Re-ranking with dispersion-corrected density functional theory (DFT-D) methods further improves the scoring. After DFT-D geometry optimization the observed crystal structure is found at the leading top of the ranking list. DFT-D methods and force field methods have been evaluated for use in predicting properties such as phase transitions upon heating, mechanical properties or intrinsic crystalline solubility. The utility of using crystal structure predictions and the associated material properties in risk assessment in connection with form selection in the drug development process is discussed.
Comparative metagenomics unveils functions and genome features of microbialite‐associated communities along a depth gradient
Authors: Saghaï Aurélien , Zivanovic Yvan , Moreira David , Benzerara Karim , Bertolino Paola , Ragon Marie , Tavera Rosaluz , López‐Archilla Ana Isabel , López‐García Purificación
Published: July 2016

Modern microbialites are often used as analogs of Precambrian stromatolites; therefore, studying the metabolic interplay within their associated microbial communities can help formulating hypotheses on their formation and long‐term preservation within the fossil record. We performed a comparative metagenomic analysis of microbialite samples collected at two sites and along a depth gradient in Lake Alchichica (Mexico). The community structure inferred from single‐copy gene family identification and long‐contig (>10 kb) assignation, consistently with previous rRNA gene surveys, showed a wide prokaryotic diversity dominated by Alphaproteobacteria, Gammaproteobacteria, Cyanobacteria, and Bacteroidetes, while eukaryotes were largely dominated by green algae or diatoms. Functional analyses based on RefSeq, COG and SEED assignations revealed the importance of housekeeping functions, with an overrepresentation of genes involved in carbohydrate metabolism, as compared with other metabolic capacities. The search for genes diagnostic of specific metabolic functions revealed the important involvement of Alphaproteobacteria in anoxygenic photosynthesis and sulfide oxidation, and Cyanobacteria in oxygenic photosynthesis and nitrogen fixation. Surprisingly, sulfate reduction appeared negligible. Comparative analyses suggested functional similarities among various microbial mat and microbialite metagenomes as compared with soil or oceans, but showed differences in microbial processes among microbialite types linked to local environmental conditions.
EUS‐guided FNA and FNB after on‐site cytological evaluation in gastric subepithelial tumors
Authors: Han Jae Pil , Lee Tae Hee , Hong Su Jin , Kim Hee Kyung , Noh Hyung Min , Lee Yun Nah , Choi Hyun Jong
Published: July 2016

Objective

Acquiring adequate tissue for immunohistochemical (IHC) analysis is important in the differential diagnosis of subepithelial tumors (SETs). In this study, we aimed to compare the diagnostic yield based on IHC analysis between endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) and EUS‐guided fine needle biopsy (EUS‐FNB) after on‐site cytological evaluation for cellularity in gastric SETs.

Methods

In 22 patients with gastric SETs, EUS‐guided tissue sampling was performed on the same SET in a randomized sequence, with EUS‐FNA followed by EUS‐FNB, or vice versa. After on‐site cytological evaluation for cellularity, the cytological and histological examinations were performed.

Results

There was a significant difference in the median number of needle passes to obtain adequate cellularity in the on‐site cytological evaluation (2.0 for EUS‐FNA vs 1.0 for EUS‐FNB, P = 0.008). The proportion of adequate cellularity on the first needle pass was significantly higher in the EUS‐FNB than in the EUS‐FNA group (68.2% vs 31.8%, P = 0.034). However, diagnosis based on IHC examination was established in 15 (68.2%) and 18 (81.8%) cases by EUS‐FNA and EUS‐FNB, respectively (P = 0.488).

Conclusions

EUS‐FNB decreases the number of needle passes to obtain adequate cellularity and yields a higher proportion of adequate cellularity during the first needle pass compared with EUS‐FNA in gastric SETs. However, there was no significant difference in diagnostic yield with IHC stain between the two procedures after on‐site cytological evaluation for adequate cellularity.
Arbuscular mycorrhizal fungi induced changes in rhizosphere, essential oil and mineral nutrients uptake in dill/common bean intercropping system
Authors: Weisany W. , Raei Y. , Salmasi S.Z. , Sohrabi Y. , Ghassemi‐Golezani K.
Published: July 2016

The fundamental aim of this research was to evaluate the effects of Funneliformis mosseae on nutrient uptake and distribution in solo cropping and intercropping of common bean Phaseolus vulgaris and dill Anethum graveolens in the field, using a factorial arrangement of treatments. The factors were seven cropping systems including (a) common bean sole cropping (40 plants m−2), (b) dill sole cropping at different densities (25, 50 and 75 plants m−2) and (c) the additive intercropping of dill/common bean (25/40, 50/40 and 75/40 plants m−2), with (+AM) or without (−AM) arbuscular mycorrhiza colonisation. In all cropping systems, AM colonisation improved dry weight and P, K, Fe, Zn and Mn contents of dill plants. Cultivable bacterial community was also increased in the dill/common bean intercropping. Yield of essential oil in dill shoot was improved as a result of AM colonisation and intercropping.
Economic insights on market structure and competition
Authors: Williams Jenny
Published: July 2016

Commentary to: Considering marijuana legalization carefully: insights for other jurisdictions from analysis for Vermont
The QT Scale: A Weight Scale Measuring the QTc Interval
Authors: Couderc Jean‐Philippe , Beshaw Connor , Niu Xiaodan , Serrano‐Finetti Ernesto , Casas Oscar , Pallas‐Areny Ramon , Rosero Spencer , Zareba Wojciech
Published: July 2016

Introduction

Despite the strong evidence of the clinical utility of QTc prolongation as a surrogate marker of cardiac risk, QTc measurement is not part of clinical routine either in hospital or in physician offices. We evaluated a novel device (“the QT scale”) to measure heart rate (HR) and QTc interval.

Method

The QT scale is a weight scale embedding an ECG acquisition system with four limb sensors (feet and hands: lead I, II, and III). We evaluated the reliability of QT scale in healthy subjects (cohort 1) and cardiac patients (cohorts 2 and 3) considering a learning (cohort 2) and two validation cohorts. The QT scale and the standard 12‐lead recorder were compared using intraclass correlation coefficient (ICC) in cohorts 2 and 3. Absolute value of heart rate and QTc intervals between manual and automatic measurements using ECGs from the QT scale and a clinical device were compared in cohort 1.

Results

We enrolled 16 subjects in cohort 1 (8 w, 8 m; 32 ± 8 vs 34 ± 10 years, P = 0.7), 51 patients in cohort 2 (13 w, 38 m; 61 ± 16 vs 58 ± 18 years, P = 0.6), and 13 AF patients in cohort 3 (4 w, 9 m; 63 ± 10 vs 64 ± 10 years, P = 0.9). Similar automatic heart rate and QTc were delivered by the scale and the clinical device in cohort 1: paired difference in RR and QTc were −7 ± 34 milliseconds (P = 0.37) and 3.4 ± 28.6 milliseconds (P = 0.64), respectively. The measurement of stability was slightly lower in ECG from the QT scale than from the clinical device (ICC: 91% vs 80%) in cohort 3.

Conclusion

The “QT scale device” delivers valid heart rate and QTc interval measurements.
Salt‐losing nephropathy in mice with a null mutation of the Clcnk2 gene
Authors: Grill A. , Schießl I. M. , Gess B. , Fremter K. , Hammer A. , Castrop H.
Published: July 2016

Aim

The basolateral chloride channel ClC‐Kb facilitates Cl reabsorption in the distal nephron of the human kidney. Functional mutations in CLCNKB are associated with Bartter's syndrome type 3, a hereditary salt‐losing nephropathy. To address the function of ClC‐K2 in vivo, we generated ClC‐K2‐deficient mice.

Methods

ClC‐K2‐deficient mice were generated using TALEN technology.

Results

ClC‐K2‐deficient mice were viable and born in a Mendelian ratio. ClC‐K2−/− mice showed no gross anatomical abnormalities, but they were growth retarded. The 24‐h urine volume was increased in ClC‐K2−/− mice (4.4 ± 0.6 compared with 0.9 ± 0.2 mL per 24 h in wild‐type littermates; P = 0.001). Accordingly, ambient urine osmolarity was markedly reduced (590 ± 39 vs. 2216 ± 132 mosmol L−1 in wild types; P < 0.0001). During water restriction (24 h), urinary osmolarity increased to 1633 ± 153 and 3769 ± 129 mosmol L−1 in ClC‐K2−/− and wild‐type mice (n = 12; P < 0.0001), accompanied by a loss of body weight of 12 ± 0.4 and 8 ± 0.2% respectively (P < 0.0001). ClC‐K2−/− mice showed an increased renal sodium excretion and compromised salt conservation during a salt‐restricted diet. The salt‐losing phenotype of ClC‐K2−/− mice was associated with a reduced plasma volume, hypotension, a slightly reduced glomerular filtration rate, an increased renal prostaglandin E2 generation and a massively stimulated renin–angiotensin system. Clckb−/− mice showed a reduced sensitivity to furosemide and were completely resistant to thiazides.

Conclusion

Loss of ClC‐K2 compromises TAL function and abolishes salt reabsorption in the distal convoluted tubule. Our data suggest that ClC‐K2 is crucial for renal salt reabsorption and concentrating ability. ClC‐K2‐deficient mice in most aspects mimic patients with Bartter's syndrome type 3.
Tumour‐selective targeting of drug metabolizing enzymes to treat metastatic cancer
Authors: Wierdl Monika , Tsurkan Lyudmila , Hatfield M Jason , Potter Philip M
Published: July 2016

Carboxylesterases (CEs) are ubiquitous enzymes responsible for the detoxification of ester‐containing xenobiotics. This hydrolysis reaction results in the formation of the corresponding carboxylic acid and alcohol. Due to their highly plastic active site, CEs can hydrolyze structurally very distinct and complex molecules. Because ester groups significantly increase the water solubility of compounds, they are frequently used in the pharmaceutical industry to make relatively insoluble compounds more bioavailable. By default, this results in CEs playing a major role in the distribution and metabolism of these esterified drugs. However, this can be exploited to selectively improve compound hydrolysis, and using specific in vivo targeting techniques can be employed to generate enhanced drug activity. Here, we seek to detail the human CEs involved in esterified molecule hydrolysis, compare and contrast these with CEs present in small mammals and describe novel methods to improve drug therapy by specific delivery of CEs to cells in vivo. Finally, we will discuss the development of such approaches for their potential application towards malignant disease.
Epithelial propionyl‐ and butyrylcholine as novel regulators of colonic ion transport
Authors: Moreno Sarah , Gerbig Stefanie , Schulz Sabine , Spengler Bernhard , Diener Martin , Bader Sandra
Published: July 2016

Background and Purpose

The colonic surface epithelium produces acetylcholine, released after the binding of propionate to GPCRs for this short‐chain fatty acid (SCFA). This epithelial acetylcholine then induces anion secretion via stimulation of acetylcholine receptors. The key enzyme responsible for acetylcholine synthesis, choline acetyltransferase, is known to be unselective as regards the fatty acid used for esterification of choline. As the colonic epithelium is permanently exposed to high concentrations of different SCFAs produced by bacterial fermentation, we investigated whether choline esters other than acetylcholine, propionylcholine and butyrylcholine, are produced by the colonic epithelium, too, and whether these ‘atypical’ esters are able to stimulate the acetylcholine receptors involved in the regulation of colonic ion transport.

Experimental Approach

Desorption electrospray ionization mass spectroscopy (DESI‐MS), Ussing chamber and Ca2+‐imaging experiments were performed on rat distal colon.

Key Results

DESI‐MS analyses revealed the production of acetylcholine, propionylcholine and butyrylcholine in the surface epithelium. Relative expression rates were 2–3% in comparison with acetylcholine. In Ussing chamber experiments, both atypical choline esters caused a concentration‐dependent increase in short‐circuit current, that is, stimulated anion secretion. Inhibitor experiments in the absence and presence of the submucosal plexus revealed the involvement of neuronal and epithelial acetylcholine receptors. While butyrylcholine obviously stimulated both nicotinic and muscarinic receptors, propionylcholine predominantly acted on muscarinic receptors.

Conclusions and Implications

These results suggest a novel pathway for communication between intestinal microbes producing SCFA and the host via modification of epithelial production of choline esters involved in the paracrine regulation of the colonic epithelium.
Cytokine and microbial profiles in relation to the clinical outcome following treatment of peri‐implantitis
Authors: Renvert Stefan , Widén Cecilia , Persson Rutger G.
Published: July 2016

Aim

To study whether cytokine levels and bacterial counts in p atients with peri‐implantitis reflect clinical treatment outcome following non‐surgical management.

Materials and Methods

Luminex magnet bead technology and checkerboard DNA–DNA hybridization were used to assess treatment outcome after treatment at the implant with the most severe peri‐implantitis in 41 participants.

Results

Study group mean age was 40.3 years (SD ± 9.9). Stable treatment outcome after 6 months (no further bone loss, probing pocket depth decrease ≥0.5 mm, no bleeding/suppuration) was identified in 9 of 41 (22%) participants. Peri‐implant crevicular fluid (PICF) levels were also lower for Il‐1β (P < 0.01), and with trends of lower cytokine levels in PICF for TNF‐α (P = 0.071), PDGFBB (P = 0.071), as well as for VEGF (vascular endothelial growth factor) (P = 0.071), and bacterial counts for Actinomyces israelii, Aggregatibacter actonomycetemcomitans (Y4), Campylobacter gracilis, Echerichia coli, Fusobacterium periodonticum, Leptotrichia buccalis, Parvimonas micra, Staphylococcus haemolyticus, Streptococcus anginosus, and Tannerella forsythia. Increasing levels of IL‐1 β and S. aureus (r2 = 0.856) were found only at implants with non‐stable outcome. A reduction of PICF levels for selected cytokines and bacteria studied had a sensitivity of 0.77, and a specificity of 0.80 against the clinical outcome as gold standard. Data analysis failed to differences in treatments (PerioFlow® versus YAG: ER laser) for changes in the expression of cytokines and bacteria studied.

Conclusions

At 6 months, clinically stable treatment outcome of peri‐implantitis is associated lower levels of putative pathogens total bacterial load with ≥30% reduction of IL1‐β, L‐6, and VEGF levels in PICF.
Sleep and Pain in Pediatric Illness: A Conceptual Review
Authors: Allen Jennifer M. , Graef Danielle M. , Ehrentraut Jennifer H. , Tynes Brooklee L. , Crabtree Valerie M.
Published: July 2016

Background

Sleep disruption is a common comorbidity of pediatric pain. Consequences of pain and disrupted sleep, evidence for the pain‐sleep relation, and how aspects of illness, treatment, and pharmacological pain management may contribute to or exacerbate these issues are presented.

Aims

This conceptual review explored the relation between pain and sleep in children diagnosed with chronic medical or developmental conditions. The goal of this review is to expand upon the literature by examining common themes in sleep disturbances associated with painful conditions across multiple pediatric illnesses. Populations reviewed include youth with intellectual and developmental disabilities (IDD), migraines, cystic fibrosis (CF), sickle cell disease (SCD), cancer, juvenile idiopathic arthritis (JIA), juvenile fibromyalgia (JFM), and functional gastrointestinal disorders (FGIDs).

Results

Consistent evidence demonstrates that children with medical or developmental conditions are more vulnerable to experiencing pain and subjective sleep complaints than healthy peers. Objective sleep concerns are common but often under‐studied. Evidence of the pain–sleep relationship exists, particularly in pediatric SCD, IDD, and JIA, with a dearth of studies directly examining this relation in pediatric cancer, JFM, CF, and FGIDs. Findings suggest that assessing and treating pain and sleep disruption is important when optimizing functional outcomes.

Conclusion

It is essential that research further examine objective sleep, elucidate the pain–sleep relationship, consider physiological and psychosocial mechanisms of this relationship, and investigate nonpharmacological interventions aimed at improving pain and sleep in vulnerable pediatric populations.
Melatonin Stimulates the SIRT1/Nrf2 Signaling Pathway Counteracting Lipopolysaccharide (LPS)‐Induced Oxidative Stress to Rescue Postnatal Rat Brain
Authors: Shah Shahid Ali , Khan Mehtab , Jo Myeung‐Hoon , Jo Min Gi , Amin Faiz Ul , Kim Myeong Ok
Published: July 2016

Aims

Lipopolysaccharide (LPS) induces oxidative stress and neuroinflammation both in vivo and in vitro. Here, we provided the first detailed description of the mechanism of melatonin neuroprotection against LPS‐induced oxidative stress, acute neuroinflammation, and neurodegeneration in the hippocampal dentate gyrus (DG) region of the postnatal day 7 (PND7) rat brain.

Methods

The neuroprotective effects of melatonin against LPS‐induced neurotoxicity were analyzed using multiple research techniques, including Western blotting, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) in PND7 rat brain homogenates and BV2 cell lysates in vitro. We also used EX527 to inhibit silent information regulator transcript‐1 (SIRT1).

Results

A single intraperitoneal (i.p) injection of LPS to PND7 rats significantly induced glial cell activation, acute neuroinflammation, reactive oxygen species (ROS) production and apoptotic neurodegeneration in hippocampal DG region after 4 h. However, the coadministration of melatonin significantly inhibited both LPS‐induced acute neuroinflammation and apoptotic neurodegeneration and improved synaptic dysfunction in the hippocampal DG region of PND7 rats. Most importantly, melatonin stimulated the SIRT1/Nrf2 (nuclear factor‐erythroid 2‐related factor 2) signaling pathway to reduce LPS‐induced ROS generation. The beneficial effects of melatonin were further confirmed in LPS‐stimulated BV2 microglia cell lines in vitro using EX527 as an inhibitor of SIRT1. LPS‐induced oxidative stress, Nrf2 inhibition, and neuroinflammation are SIRT1‐dependent in BV2 microglia cell lines.

Conclusion

These results demonstrated that melatonin treatment rescued the hippocampal DG region of PND7 rat brains against LPS‐induced oxidative stress damage, acute neuroinflammation, and apoptotic neurodegeneration via SIRT1/Nrf2 signaling pathway activation.
Viral colonization in exhaled breath condensate of lung cancer patients: Possible role of EBV and CMV
Authors: Carpagnano Giovanna E. , Lacedonia Donato , Natalicchio Maria Iole , Cotugno Grazia , Zoppo Luigi , Martinelli Domenico , Antonetti Raffaele , Foschino‐Barbaro Maria Pia
Published: July 2016

Introduction

Today, an increasing interest is being addressed to the viral etiology of lung tumors. As a consequence, research efforts are currently being directed to the identification of the new viruses involved in lung carcinogenesis toward which the screening programs could be directed.

Objectives

The aim of this study was to investigate the airways colonization by the Epstein‐Barr virus (EBV) and Citomegalovirus (CMV) in patients affected by lung cancer using, as a respiratory non‐invasive sample, the exhaled breath condensate (EBC).

Methods

About 70 lung‐cancer patients and 40 controls were enrolled. All subjects underwent bronchial brushing and EBC collection. EBV‐DNA and CMV‐DNA were evaluated in both samples by real‐time PCR assay.

Results

They were able to detect EBV and CMV in the EBC. An increase of the EBV positivity in non‐small cell lung cancer (NSCLC) patients compared with controls and of the CMV in advanced stages of lung cancer were observed. The association of the positivity of the cytology and the CMV test (in EBC or brushing) slightly increased the sensitivity of malignant diagnosis.

Conclusion

EBV and CMV resulted detectable in the EBC. In consideration of the potential involvement of these viruses in lung cancer, which was confirmed in this study, future studies in this direction were supported.
Colonoscopy bowel preparation quality improvement for patients with decompensated cirrhosis undergoing evaluation for liver transplantation
Authors: Clayton Donnesha B. , Palmer William C. , Robison Sarah W. , Heckman Michael G. , Chimato Nicolette T. , Harnois Denise M. , Francis Dawn L.
Published: July 2016

Background/Aims

Inadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education.

Methods

A total of 121 patients undergoing evaluation at our institution prior to implementation of the quality improvement initiative and 91 patients undergoing evaluation after implementation were included. The initiative was an educational intervention via a 6‐minute colonoscopy and split‐prep bowel preparation educational video during the initial liver transplantation evaluation visit for all patients with scheduled colonoscopy.

Results

Inadequate bowel preparation was observed in 36 patients (29.8%) in the pre‐intervention period compared to 29 patients (31.9%) in the post‐intervention period. This corresponded to a lack of a significant difference in both single‐variable analysis and multivariable analysis. Of note, there was a significantly higher rate of inadequate bowel preparation as ascites worsened (P=.028).

Conclusion

Patient educational video failed to improve bowel preparations in patients undergoing colonoscopy with decompensated cirrhosis.
Effect of moderately intense perioperative glucose control on renal allograft function: a pilot randomized controlled trial in renal transplantation
Authors: Parekh Justin , Roll Garrett R. , Wisel Steven , Rushakoff Robert J. , Hirose Ryutaro
Published: July 2016

Recipient diabetes accounts for ~34% of end‐stage renal disease in patients awaiting renal transplantation and has been linked to poor graft function. We conducted a single‐center, open‐label, randomized controlled trial to determine whether moderately intense glucose control during allograft reperfusion would reduce the incidence of poor graft function. Adult diabetics undergoing deceased donor renal transplant were randomized to moderately intense glucose control (n=30) or standard control (n=30). The primary outcome was poor graft function (dialysis within seven days of transplant or failure of serum creatinine to fall by 10% for three consecutive days). Recipients with moderately intense glucose control had less poor graft function in the intention‐to‐treat (43.3% vs 73.3%, P=.02) and per‐protocol analysis (43.2% vs 81%, P<.01). Recipients with moderately intense control also had higher glomerular filtration rate (GFR) at 30 days after transplant in the per‐protocol and intention‐to‐treat analyses. There were no episodes of severe hypoglycemia in either group and no differences in mortality, seizures, stroke, graft loss, or biopsy‐proven rejection. Moderately intense glucose control at the time of allograft reperfusion reduces the incidence of poor graft function in diabetic renal transplant recipients and improves glomerular filtration rate at 30 days.