bluuebunny/crossref_metadata_2025 huggingface dataset:
Elite Male and Female 800-m Runners’ Display of Different Pacing Strategies During Season-Best Performances
Authors: Filipas Luca , Nerli Ballati Emiliano , Bonato Matteo , La Torre Antonio , Piacentini Maria Francesca
Published: May 2018

Purpose: To analyze the pacing profiles of the world’s top 800-m annual performances between 2010 and 2016, comparing men’s and women’s strategies. Methods: A total of 142 performances were characterized for overall race times and 0-to-200-m, 200-to-400-m, 400-to-600-m, and 600-to-800-m split times using available footage from YouTube. Only the best annual performance for each athlete was considered. Overall race and split speed were calculated so that each lap speed could be expressed as a percentage of the mean race speed. Results: The mean speed of the men’s 800-m was 7.73 (0.06) m·s−1, with the 0-to-200-m split faster than the others. After the first split, the speed decreased significantly during the 3 subsequent splits (P < .001). The mean speed of the women’s 800-m was 6.77 (0.05) m·s−1, with a significative variation in speed during the race (P < .001). The first split was faster than the others (P < .001). During the rest of the race, speed was almost constant, and no difference was observed between the other splits. Comparison between men and women revealed that there was an interaction between split and gender (P < .001), showing a different pacing behavior in 800-m competitions. Conclusions: The world’s best 800-m performances revealed an important difference in the pacing profile between men and women. Tactics could play a greater role in this difference, but physiological and behavioral characteristics are likely also important.
Short-Term Effects of Rolling Massage on Energy Cost of Running and Power of the Lower Limbs
Authors: Giovanelli Nicola , Vaccari Filippo , Floreani Mirco , Rejc Enrico , Copetti Jasmine , Garra Marco , Biasutti Lea , Lazzer Stefano
Published: May 2018

Purpose: Self-myofascial release (SMFR) is a type of self-massage that is becoming popular among athletes. However, SMFR’s effects on running performance have not yet been investigated. The aim of this study was to evaluate the effects of SMFR on the cost of running (Cr). In addition, the authors evaluated the effects of SMFR on lower-limb muscle power. Methods: Cr and lower-limb muscle power during squat jump (SJ) and countermovement jump (CMJ) were measured before (PRE), immediately after (POST), and 3 h after (POST 3h) an SMFR protocol (experimental condition). In the control-condition testing session, the same measurements were performed without undergoing the SMFR protocol. Experimental and control conditions were tested in a randomized order. Results: Cr at POST trended to increase compared with PRE (+6.2% [8.3%], P = .052), whereas at POST 3h, Cr was restored to PRE values (+0.28% [9.5%], P = .950). In the experimental condition, no significant effect of time was observed for maximal power exerted during SJ. By contrast, maximal power exerted during CMJ at POST and at POST 3h was significantly higher than that observed at PRE (+7.9% [6.3%], P = .002 and +10.0% [8.7%], P = .004, respectively). The rate of force development measured during CMJ also increased after SMFR, reaching statistical significance at 200 ms from force onset at POST 3h (+38.9%, P = .024). Conclusions: An acute use of foam rollers for SMFR performed immediately prior to running may negatively affect endurance running performance, but its use should be added before explosive motor performances that include stretch-shortening cycles.
Animal tests surge under new U.S. chemical law
Authors: Zainzinger Vanessa
Published: May 2018

2016 measure urged EPA to reduce animal use, but numbers are rising instead.
Magnetic seismology of interstellar gas clouds: Unveiling a hidden dimension
Authors: Tritsis Aris , Tassis Konstantinos
Published: May 2018

A vibrating molecular cloud in three dimensions

Molecular clouds are relatively dense assemblies of interstellar dust and gas (mostly molecular hydrogen) from which stars form. Determining the three-dimensional (3D) morphology of these clouds is difficult because we only see a 2D projection of them onto the sky. While examining far-infrared observations of the nearby Musca cloud, Tritsis and Tassis discovered that the cloud is vibrating with magnetohydrodynamic waves. The pattern of vibrations reveals the 3D structure and shows that Musca is a sheet seen edge-on, not a filament as previously assumed.

Science
, this issue p.
635
Efficient coding explains the universal law of generalization in human perception
Authors: Sims Chris R.
Published: May 2018

Balancing costs and performance

Deciding whether a novel object is another instance of something already known or an example of something different is an easily solved problem. Empirical mapping of human performance across a wide range of domains has established an exponential relationship between the generalization gradient and interstimuli distance. Sims now shows that this relationship can be derived from a consideration of the costs of optimal information coding.

Science
, this issue p.
652
Recent Asian origin of chytrid fungi causing global amphibian declines
Authors: O’Hanlon Simon J. , Rieux Adrien , Farrer Rhys A. , Rosa Gonçalo M. , Waldman Bruce , Bataille Arnaud , Kosch Tiffany A. , Murray Kris A. , Brankovics Balázs , Fumagalli Matteo , Martin Michael D. , Wales Nathan , Alvarado-Rybak Mario , Bates Kieran A. , Berger Lee , Böll Susanne , Brookes Lola , Clare Frances , Courtois Elodie A. , Cunningham Andrew A. , Doherty-Bone Thomas M. , Ghosh Pria , Gower David J. , Hintz William E. , Höglund Jacob , Jenkinson Thomas S. , Lin Chun-Fu , Laurila Anssi , Loyau Adeline , Martel An , Meurling Sara , Miaud Claude , Minting Pete , Pasmans Frank , Schmeller Dirk S. , Schmidt Benedikt R. , Shelton Jennifer M. G. , Skerratt Lee F. , Smith Freya , Soto-Azat Claudio , Spagnoletti Matteo , Tessa Giulia , Toledo Luís Felipe , Valenzuela-Sánchez Andrés , Verster Ruhan , Vörös Judit , Webb Rebecca J. , Wierzbicki Claudia , Wombwell Emma , Zamudio Kelly R. , Aanensen David M. , James Timothy Y. , Gilbert M. Thomas P. , Weldon Ché , Bosch Jaime , Balloux François , Garner Trenton W. J. , Fisher Matthew C.
Published: May 2018

Panzootic chytrid fungus out of Asia

Species in the fungal genus
Batrachochytrium
are responsible for severe declines in the populations of amphibians globally. The sources of these pathogens have been uncertain. O'Hanlon
et al.
used genomics on a panel of more than 200 isolates to trace the source of the frog pathogen
B. dendrobatidis
to a hyperdiverse hotspot in the Korean peninsula (see the Perspective by Lips). Over the past century, the trade in amphibian species has accelerated, and now all lineages of
B. dendrobatidis
occur in traded amphibians; the fungus has become ubiquitous and is diversifying rapidly.

Science
, this issue p.
621
; see also p.
604
Asymmetric nucleophilic fluorination under hydrogen bonding phase-transfer catalysis
Authors: Pupo Gabriele , Ibba Francesco , Ascough David M. H. , Vicini Anna Chiara , Ricci Paolo , Christensen Kirsten E. , Pfeifer Lukas , Morphy John Richard , Brown John M. , Paton Robert S. , Gouverneur Véronique
Published: May 2018

H-bond to deliver fluoride

Simple fluoride salts are theoretically convenient reagents for carbon-fluorine bond formation. In practice, they are often insoluble in the solvents that dissolve their reaction partners. Pupo
et al.
developed urea-based catalysts that make fluoride soluble through hydrogen bonding. Moreover, their chiral substituents bias the reaction toward one of two mirror image products of C–F bond formation. This strategy should be applicable to the asymmetric addition of other salts, too.

Science
, this issue p.
638
Results roll in from the dinosaur renaissance
The Rise and Fall of the Dinosaurs: A New History of a Lost World
Steve Brusatte
Morrow, 2018. 416 pp.
Authors: Arbour Victoria
Published: May 2018

An enjoyable round-the-world narrative synthesizes recent paleontological discoveries
Structure, mechanism, and regulation of the chloroplast ATP synthase
Authors: Hahn Alexander , Vonck Janet , Mills Deryck J. , Meier Thomas , Kühlbrandt Werner
Published: May 2018

Protons find a path

Adenosine triphosphate (ATP) synthases are dynamos that interconvert rotational and chemical energy. Capturing the complete structure of these multisubunit membrane-bound complexes has been hindered by their inherent ability to adopt multiple conformations. Srivastava
et al.
used protein engineering to freeze mitochondrial ATP synthase from yeast in a single conformation and obtained a structure with the inhibitor oligomycin, which binds to the rotating c-ring within the membrane. Hahn
et al.
show that chloroplast ATP synthase contains a built-in inhibitor triggered by oxidizing conditions in the dark chloroplast. The mechanisms by which these machines are powered are remarkably similar: Protons are shuttled through a channel to the membrane-embedded c-ring, where they drive nearly a full rotation of the rotor before exiting through another channel on the opposite side of the membrane (see the Perspective by Kane).

Science
, this issue p.
eaas9699
, p.
eaat4318
; see also p.
600
Open minds
How to Change Your Mind
Michael Pollan
Penguin Press, 2018. 479 pp.
Authors: Pohl Nicola
Published: May 2018

A revival in the scientific study of psychedelics prompts a journalist to take a trip
Resolving the neutron lifetime puzzle
Authors: Mumm Pieter
Published: May 2018

A measurement of trapped neutrons dramatically improves control of systematic uncertainties
A Multimodal Imaging Approach Enables
In Vivo
Assessment of Antifungal Treatment in a Mouse Model of Invasive Pulmonary Aspergillosis
Authors: Poelmans Jennifer , Himmelreich Uwe , Vanherp Liesbeth , Zhai Luca , Hillen Amy , Holvoet Bryan , Belderbos Sarah , Brock Matthias , Maertens Johan , Vande Velde Greetje , Lagrou Katrien
Published: May 2018

Aspergillus fumigatus
causes life-threatening lung infections in immunocompromised patients. Mouse models are extensively used in research to assess the
in vivo
efficacies of antifungals. In recent years, there has been an increasing interest in the use of noninvasive imaging techniques to evaluate experimental infections. However, single imaging modalities have limitations concerning the type of information they can provide. In this study, magnetic resonance imaging and bioluminescence imaging were combined to obtain longitudinal information on the extent of developing lesions and fungal load in a leukopenic mouse model of invasive pulmonary aspergillosis (IPA). This multimodal imaging approach was used to assess changes occurring within lungs of infected mice receiving voriconazole treatment starting at different time points after infection. The results showed that IPA development depends on the inoculum size used to infect animals and that disease can be successfully prevented or treated by initiating intervention during early stages of infection. Furthermore, we demonstrated that a reduction in fungal load is not necessarily associated with the disappearance of lesions on anatomical lung images, especially when antifungal treatment coincides with immune recovery. In conclusion, multimodal imaging allows an investigation of different aspects of disease progression or recovery by providing complementary information on dynamic processes, which are highly useful for assessing the efficacy of (novel) therapeutic compounds in a time- and labor-efficient manner.
Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir
Authors: Focà Emanuele , Calcagno Andrea , Bonito Andrea , Cusato Jessica , Domenighini Elisabetta , D'Avolio Antonio , Quiros Roldan Eugenia , Trentini Laura , Castelnuovo Filippo , Di Perri Giovanni , Castelli Francesco , Bonora Stefano
Published: May 2018

Atazanavir-ritonavir concentrations change over time during pregnancy in HIV-positive patients; the impact of genetic variants is unknown. Twenty patients were enrolled in this study; plasma and intracellular concentrations of antiretrovirals were measured, in addition to single-nucleotide polymorphisms in transport-related genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1- and pregnane-X-receptor-encoding genes affected third-trimester atazanavir exposure. In this prospective study, genetic variants partially explained the observed interpatient variability in third-trimester exposure to antiretrovirals.
Identification and Characterization of Salmonella enterica Serotype Newport Isolates with Decreased Susceptibility to Ciprofloxacin in the United States
Authors: Campbell D. , Tagg K. , Bicknese A. , McCullough A. , Chen J. , Karp B. E. , Folster J. P.
Published: May 2018

Nontyphoidal
Salmonella
(NTS) causes an estimated 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths each year in the United States. Decreased susceptibility to ciprofloxacin (DSC) has historically been associated with chromosomal mutations of the quinolone resistance determining region (QRDR), but plasmid-mediated quinolone resistance (PMQR) genes are increasing. To investigate DSC among
Salmonella enterica
serotype Newport strains, we examined 40 isolates from 1996 to 2016 with DSC. Thirty isolates (71%) contained the PMQR gene
qnrB
and eight isolates (19%) contained a QRDR.
Association of Mycobacterium Proteins with Lipid Droplets
Authors: Armstrong Richard M. , Carter Dominique C. , Atkinson Samantha N. , Terhune Scott S. , Zahrt Thomas C.
Published: May 2018

Mycobacterium
spp. are one of the few prokaryotes known to produce lipid droplets (LDs), and their production has been linked to aspects of persistent infection by
M. tuberculosis
. Unfortunately, little is known about LD production in these organisms, including how LDs are formed, their function, or the identity of proteins that associate with them. In this study, an established
M. tuberculosis
LD protein and a surrogate
Mycobacterium
host were used as model systems to study the interactions between proteins and LDs in bacteria. Through these studies, we identified a commonly occurring protein motif that is able to facilitate the association of proteins to LDs in prokaryotes.
Roles of Fc Domain and Exudation in L2 Antibody-Mediated Protection against Human Papillomavirus
Authors: Wang Joshua W. , Wu Wai Hong , Huang Tsui-Chin , Wong Margaret , Kwak Kihyuck , Ozato Keiko , Hung Chien-Fu , Roden Richard B. S.
Published: May 2018

At least 15 alpha HPV types are causative agents for 5% of all cancers worldwide, and beta types have been implicated in nonmelanoma skin cancer, whereas others produce benign papillomas, such as genital warts, associated with considerable morbidity and health systems costs. Vaccines targeting the minor capsid protein L2 have the potential to provide broad-spectrum immunity against medically relevant HPVs of divergent genera via the induction of broadly cross-neutralizing serum IgG. Here we examine the mechanisms by which L2-specific serum IgG reaches the viral inoculum in the genital tract to effect protection. Abrasion of the vaginal epithelium allows the virus to access and infect basal keratinocytes, and our findings suggest that this also permits the local exudation of neutralizing IgG and vaccine-induced sterilizing immunity. We also demonstrate the importance of Fc-mediated phagocytosis of L2 antibody-virion complexes for humoral immunity, a protective mechanism that is not detected by current
in vitro
neutralization assays.
How to use saturation monitoring in newborns
Authors: McVea Steven , McGowan Michael , Rao Bharathi
Published: May 2018

Pulse oximetry is a first-line monitoring tool, used in neonatal medicine routinely as a part of continuous monitoring during intensive care. It is also used to guide response to resuscitation and as a screening tool for congenital heart disease. Despite its widespread use, many healthcare providers are unaware of the underlying principles and limitations of pulse oximetry in neonates. In this article, we will discuss the physiological and technological principles behind the use of saturation monitoring and its use in neonatal practice.
What is the impact of water sanitation and hygiene in healthcare facilities on care seeking behaviour and patient satisfaction? A systematic review of the evidence from low-income and middle-income countries
Authors: Bouzid Maha , Cumming Oliver , Hunter Paul R
Published: May 2018

Patient satisfaction with healthcare has clear implications on service use and health outcomes. Barriers to care seeking are complex and multiple and delays in seeking care are associated with significant morbidity and mortality. We sought to assess the relationship between water, sanitation and hygiene (WASH) provision in healthcare facilities (HCF) and patient satisfaction/care seeking behaviour in low-income and middle-income countries. Pubmed and Medline Ovid were searched using a combination of search terms. 984 papers were retrieved and only 21 had a WASH component warranting inclusion. WASH was not identified as a driver of patient satisfaction but poor WASH provision was associated with significant patient dissatisfaction with infrastructure and quality of care. However, this dissatisfaction was not sufficient to stop patients from seeking care in these poorly served facilities. With specific regard to maternal health services, poor WASH provision was the reason for women choosing home delivery, although providers’ attitudes and interpersonal behaviours were the main drivers of patient dissatisfaction with maternal health services. Patient satisfaction was mainly assessed via questionnaires and studies reported a high risk of courtesy bias, potentially leading to an overestimation of patient satisfaction. Patient satisfaction was also found to be significantly affected by expectation, which was strongly influenced by patients’ socioeconomic status and education. This systematic review also highlighted a paucity of research to describe and evaluate interventions to improve WASH conditions in HCF in low-income setting with a high burden of healthcare-associated infections. Our review suggests that improving WASH conditions will decrease patience dissatisfaction, which may increase care seeking behaviour and improve health outcomes but that more rigorous research is needed.
General practitioners providing non-urgent care in emergency department: a natural experiment
Authors: Uthman Olalekan A , Walker Clare , Lahiri Sudakshina , Jenkinson David , Adekanmbi Victor , Robertson Wendy , Clarke Aileen
Published: May 2018

Objective

To examine whether care provided by general practitioners (GPs) to non-urgent patients in the emergency department differs significantly from care provided by usual accident and emergency (A&E) staff in terms of process outcomes and A&E clinical quality indicators.

Design

Propensity score matched cohort study.

Setting

GPs in A&E colocated within the University Hospitals Coventry and Warwickshire NHS Trust between May 2015 and March 2016.

Participants

Non-urgent attendances visits to the A&E department.

Main outcomes

Process outcomes (any investigation, any blood investigation, any radiological investigation, any intervention, admission and referrals) and A&E clinical indicators (spent 4 hours plus, left without being seen and 7-day reattendance).

Results

A total of 5426 patients seen by GPs in A&E were matched with 10 852 patients seen by emergency physicians (ratio 1:2). Compared with standard care in A&E, GPs in A&E significantly: admitted fewer patients (risk ratio (RR) 0.28, 95% CI 0.25 to 0.31), referred fewer patients to other specialists (RR 0.31, 95% CI 0.24 to 0.40), ordered fewer radiological investigations (RR 0.38, 95% CI 0.34 to 0.42), ordered fewer blood tests (0.57, 95% CI 0.52 to 0.61) and ordered fewer investigations (0.93, 95% CI 0.90 to 0.96). However, they intervened more, offered more primary care follow-up (RR 1.78, 95% CI 1.67 to 1.89) and referred more patients to outpatient and other A&E clinics (RR 2.29, 95% CI 2.10 to 2.49). Patients seen by GPs in A&E were on average less likely to spend 4 hours plus in A&E (RR 0.37, 95% CI 0.30 to 0.45) compared with standard care in A&E. There was no difference in reattendance after 7 days (RR 0.96, 95% CI 0.84 to 1.09).

Conclusion

GPs in A&E tended to manage self-reporting minor cases with fewer resources than standard care in A&E, without increasing reattendance rates.
Senior doctor triage (SDT), a qualitative study of clinicians’ views on senior doctors’ involvement in triage and early assessment of emergency patients
Authors: Abdulwahid Maysam Ali , Turner Janette , Mason Suzanne M
Published: May 2018

Introduction

Despite the focus during the last decade on introducing interventions such as senior doctor initial assessment or senior doctor triage (SDT) to reduce emergency department (ED) crowding, there has been little attempt to identify the views of emergency healthcare professionals on such interventions. The aim of this study was to gain an understanding of SDT from the perspective of emergency hospital staff. A secondary aim of this study was to develop a definition of SDT based on the interview findings and the available literature on this process.

Methods

Qualitative semi-structured telephone interviews were conducted with participants of different backgrounds including senior doctors, nurses, paramedics and ED managers. Textual data were analysed using a template analysis approach.

Results

27 participants from 13 EDs across England were interviewed. SDT was viewed as a safety mechanism and a measure to control patient flow. The most prominent positive aspect was the ability to initiate early investigations and treatment. Various shortcomings of SDT were described such as the lack of standardisation of the process and its cost implications. Participants identified a number of barriers to this process including insufficient resources and exit block, and called for solutions focused on these issues. A proposed definition of an ‘ideal’ SDT was developed where it is described as a systematic brief assessment of patients arriving at the ED by a senior doctor-led team, which takes place in a dedicated unit. The aim of this assessment is to facilitate early investigation and management of patients, early patient disposition and guide junior staff to deliver safe and high-quality clinical care.

Conclusion

This is the first national study to explore the opinions of various emergency and managerial staff on the SDT model. It revealed variable interpretations of this model and what it can and cannot offer. This has led to a standard definition of the SDT process, which can be useful for clinicians and researchers in emergency care.
Prognostic significance of repeated brain natriuretic peptide measurements after percutaneous transluminal septal myocardial ablation in patients with drug-refractory hypertrophic obstructive cardiomyopathy
Authors: Akita Keitaro , Tsuruta Hikaru , Yuasa Shinsuke , Murata Mitsushige , Fukuda Keiichi , Maekawa Yuichiro
Published: May 2018

Objectives

To evaluate whether repeated brain natriuretic peptide (BNP) measurements after percutaneous transluminal septal myocardial ablation (PTSMA) provide prognostic information regarding the response to PTSMA in patients with drug-refractory hypertrophic obstructive cardiomyopathy (HOCM).

Background

Plasma BNP levels are associated with clinical outcomes in patients with HOCM. However, the prognostic value of plasma BNP level changes before and after PTSMA remains unclear.

Methods

We measured the plasma BNP levels serially before and after PTSMA, and evaluated the relationship between the changes in plasma BNP levels and clinical improvement in 47 patients. The patients were assigned to two groups based on the reduction in the New York Heart Association class ≥1 (good responder) or <1 (poor responder) before and after PTSMA. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to measure health status.

Results

The plasma BNP levels gradually decreased after PTSMA, although the levels plateaued 3 months until 12 months after PTSMA. Although the plasma BNP levels and resting left ventricular outflow tract peak pressure gradient before PTSMA were comparable between the groups, the ratio of the BNP levels before and after PTSMA in the good responder group was significantly lower than that in the poor responder group (0.43 (range, 0.24–0.68) vs 0.78 (range, 0.62–0.93), p=0.002). The KCCQ score changes in the good responder group were significantly higher than those in the poor responder group.

Conclusions

The plasma BNP level ratio was associated with long-term clinical improvement of heart failure after PTSMA for drug-refractory HOCM.
Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung
Authors: Tagalakis Aristides D , Munye Mustafa M , Ivanova Rositsa , Chen Hanpeng , Smith Claire M , Aldossary Ahmad M , Rosa Luca Z , Moulding Dale , Barnes Josephine L , Kafetzis Konstantinos N , Jones Stuart A , Baines Deborah L , Moss Guy W J , O’Callaghan Christopher , McAnulty Robin J , Hart Stephen L
Published: May 2018

Introduction

Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport.

Methods

We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air–liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (Vt), short circuit current (Isc), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections.

Results

Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced Vt, the amiloride-sensitive Isc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%.

Conclusion

Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo.
Effect of carbohydrate restriction-induced weight loss on aortic pulse wave velocity in overweight men and women
Authors: Syed-Abdul Majid M. , Hu Qiong , Jacome-Sosa Miriam , Padilla Jaume , Manrique-Acevedo Camila , Heimowitz Colette , Parks Elizabeth J.
Published: May 2018

Increased aortic stiffness, measured by carotid-to-femoral pulse wave velocity (PWV), is an independent predictor of cardiovascular disease, and past data have shown that low-fat and low-energy diets, fed for 8–24 weeks, lower PWV. The purpose of this study was to determine whether a reduction in PWV would be achieved by dietary carbohydrate (CHO) restriction, shown to bring about weight loss over a shorter timeframe. Men (n = 10, age: 41.8 ± 10.2 years, BMI: 34.2 ± 3.0 kg/m2 (mean ± SD)) and women (n = 10, age: 38.6 ± 6.1 years, BMI: 33.5 ± 3.8 kg/m2) with characteristics of insulin resistance and the metabolic syndrome consumed a structured, CHO-restricted diet for 4 weeks (energy deficit, 645 kcal/day). For the whole group, subjects lost 5.4% ± 0.5% (P < 0.001) of body weight and experienced significant reductions in blood pressure (6%–8%), plasma insulin (34%), and triglycerides (34%). PWV was reduced by 6% ± 2% (7.1 ± 0.2 m/s to 6.7 ± 0.2 m/s, P = 0.008) and surprisingly, in women, it fell significantly (from 7.2 ± 0.3 m/s to 6.3 ± 0.3 m/s, P = 0.028), while no changes were observed in men (7.2 ± 0.3 vs. 7.0 ± 0.3 m/s, P = 0.144). This is the first study to demonstrate that weight loss can improve PWV in as little as 4 weeks and that dietary CHO restriction may be an effective treatment for reducing aortic stiffness in women. Future studies are needed to establish the mechanisms by which dietary CHO restriction may confer more cardiovascular benefits to women than to men.
From hitchhiker to hijacker: pathogen exploitation of endosomal phosphoinositides
Authors: Qiu Shirley , Côté Marceline
Published: May 2018

Signalling through phosphoinositide lipids is essential for regulating many cellular processes, including endosomal trafficking. A number of intracellular pathogens have found ways to subvert host trafficking pathways via exploitation of endosomal phosphoinositides. This review will discuss how pathogens such as bacteria, viruses, and eukaryotic parasites depend on endosomal phosphoinositides for infection as well as the mechanisms through which some are able to actively manipulate these signalling lipids to facilitate invasion, survival, replication, and immune evasion.
FORCED WAVES PROPAGATION IN GREAT LIVING ARTERIES TISSUES
Authors: BARBIERI ISABELLA , CAROLI EZIO , PALLOTTI GIOVANNI
Published: May 2018

Starting from experimental data, this work exploit the similarity of pressure and axial wave’s propagation of both pressure and axial waves in large vessel (e.g., aorta) with the solution of a mathematical model developed to describe the motion of acoustic waves in solid. In particular, we show how the motion parameters derived by fitting the experimental data measured in living dog arteries are related to mechanical properties of the vessel tissue using the same theoretical model. Furthermore, we briefly discuss the consequence on the predicted forced wave motion of inferring from experimental data a phase velocity depending from frequency.
Solvent effects on cycloaddition reactions of potent spin-trapping probe N-tert-butylmethanimine N-oxide: A DFT study
Authors: Acharjee Nivedita
Published: May 2018

[Formula: see text]-tert-butylmethanimine [Formula: see text]-oxide is a potent spin-trapping probe for biologically important radicals, and this nitrone undergoes complete regioselective cycloadditions to less electron-deficient monosubstituted olefins. In the present study, solvent effects on the cycloaddition of this nitrone to styrene have been theoretically studied in terms of the global properties of the reactants, electrophilic and nucleophilic Parr function analysis and the activation and reaction energies of located transition states and products. Formation energies of optimized radical adducts were computed to determine their stabilities in different solvents. The cycloaddition is predicted to be completely ortho regioselective which is in complete agreement with experiments and involved earlier C–C bond formation owing to the insufficient depopulation of [Formula: see text]-conjugated carbon atom in styrene and shows varying asymmetry indices in different solvents. Decrease in activation parameters and increase in stability of cycloadducts are predicted with decreasing solvent polarity. Aqueous media destabilize the radical adducts as predicted from the calculated formation energy, enthalpy and free energy of reaction. Hydroxyl as well as methyl radical adducts are predicted to be more stable than superoxide anion radical adducts. These predictions are in complete agreement with the experiments.
World Class Manufacturing Operations Management: Scale Development and LHEMI Model Proposition
Authors: Oliveira Paulo S. G. , da Silva Luciano F. , d’Silva Dirceu , Tecilla Maria C. , da Silva Rodrigo C.
Published: May 2018

This paper aims to create a quantitative model of World Class Manufacturing (WCM) using the findings of Oliveira (2015) who identified six constructs using the PLS-PM method to create a WCM-LHEMI model, which is an acronym for Lean Manufacturing, Human Resource Management, Environmental Practices, and Marketing Integration. We created a questionnaire using the variables that exploratory factor analyses identified as consistent and distributed it to 1000 professionals using the LinkedIn professional network. From these, our final sample consisted of 180 completed questionnaires, which exceeded the 68 answers needed to have an adequate sample based on suggestions by G*Power Software. Eleven hypotheses were analyzed and six were accepted and considered valid. A goal of this research was to examine the professional’s perception about the need for enterprises to have environmental practices to become WCM enterprises. A main contribution of this study was to propose a WCM model using professional perceptions about what denotes a WCM enterprise through a PLS Statistics method.
Induction of gut proteasome activity in hemorrhagic shock and its recovery by treatment with diphenyldihaloketones CLEFMA and EF24
Authors: Rao Geeta , Houson Hailey , Nkepang Gregory , Yari Hooman , Teng Chengwen , Awasthi Vibhudutta
Published: May 2018

Multiorgan failure in hemorrhagic shock is triggered by gut barrier dysfunction and consequent systemic infiltration of proinflammatory factors. Our previous study has shown that diphenyldihaloketone drugs 4-[3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidinyl]-4-oxo-2-butenoic acid (CLEFMA) and 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone (EF24) restore gut barrier dysfunction and reduce systemic inflammatory response in hemorrhagic shock. We investigated the effect of hemorrhagic shock on proteasome activity of intestinal epithelium and how CLEFMA and EF24 treatments modulate proteasome function in hemorrhagic shock. CLEFMA or EF24 (0.4 mg/kg) were given 1 h after withdrawing 50% of blood from Sprague-Dawley rats; no other resuscitation was provided. After another 5 h of compensation, small gut was collected to process tissue for proteasome activity, immunoblotting, and mRNA levels of genes responsible for unfolded-protein response (XBP1, ATF4, glucose-regulated protein of 78/95 kDa, and growth arrest and DNA damage inducible genes 153/34), polyubiquitin B and C, and immunoproteasome subunits β type-8 and -10 and proteasome activator subunit 1. We found that hemorrhagic shock induced proteasome activity in gut tissue and reduced the amounts of ubiquitinated proteins displayed on antiubiquitin immunoblots. However, simultaneous induction of unfolded-protein response or immunoproteasome genes was not observed. CLEFMA and EF24 treatments abolished the hemorrhagic shock-induced increase in proteasome activity. Further investigations revealed that the induction of proteasome in hemorrhagic shock is associated with disassembly of 26S proteasome; CLEFMA and EF24 prevented this disassembly. Consistent with these data, CLEFMA and EF24 reduced hemorrhagic shock-induced degradation of 20S substrate ornithine decarboxylase in gut tissue. These results suggest that activated proteasome plays an important role in ischemic gut pathophysiology, and it can be a druggable target in shock-induced gut dysfunction.

NEW & NOTEWORTHY Ischemic injury to the gut is a trigger for the systemic inflammatory response and multiple organ failure in trauma and hemorrhagic shock. We show for the first time that hemorrhagic shock induces the gut proteasome activity by engendering 26S proteasome disassembly. Diphenyldihaloketones 4-[3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidinyl]-4-oxo-2-butenoic acid and 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone treatment prevented the 26S disassembly. Understanding the role of proteasome in shock-associated gut injury will assist in the development of therapeutic means to address it.
Increased TASK channel-mediated currents underlie high-fat diet induced vagal afferent dysfunction
Authors: Park Sung Jin , Yu Yang , Wagner Brittany , Valinsky William C. , Lomax Alan E. , Beyak Michael J.
Published: May 2018

We have previously demonstrated that satiety sensing vagal afferent neurons are less responsive to meal-related stimuli in obesity because of reduced electrical excitability. As leak K+ currents are key determinants of membrane excitability, we hypothesized that leak K+ currents are increased in vagal afferents during obesity. Diet-induced obesity was induced by feeding C57Bl/6J mice a high-fat diet (HFF) (60% energy from fat) for 8–10 wk. In vitro extracellular recordings were performed on jejunal afferent nerves. Whole cell patch-clamp recordings were performed on mouse nodose ganglion neurons. Leak K+ currents were isolated using ion substitution and pharmacological blockers. mRNA for TWIK-related acid-sensitive K+ (TASK) subunits was measured using quantitative real-time PCR. Intestinal afferent responses to nutrient (oleate) and non-nutrient (ATP) stimuli were significantly decreased in HFF mice. Voltage clamp experiments revealed the presence of a voltage-insensitive resting potassium conductance that was increased by external alkaline pH and halothane, known properties of TASK currents. In HFF neurons, leak K+ current was approximately doubled and was reduced by TASK1 and TASK3 inhibitors. The halothane sensitive current was similarly increased. Quantitative PCR revealed the presence of mRNA encoding TASK1 (KCNK3) and TASK3 (KCNK9) channels in nodose neurons. TASK3 transcript was significantly increased in HFF mice. The reduction in vagal afferent excitability in obesity is due in part to an increase of resting (leak) K+ conductance. TASK channels may account for the impairment of satiety signaling in diet-induced obesity and thus is a therapeutic target for obesity treatment.

NEW & NOTEWORTHY This study characterized the electrophysiological properties and gene expression of the TWIK-related acid-sensitive K+ (TASK) channel in vagal afferent neurons. TASK conductance was increased and contributed to decreased excitability in diet-induced obesity. TASK channels may account for the impairment of satiety signaling in diet-induced obesity and thus is a promising therapeutic target.
Changes in the pattern of fibrosis in the rat lung with repetitive orotracheal instillations of gastric contents: evidence of persistent collagen accumulation
Authors: Ayala Pedro , Torres Jorge , Vivar Raúl , Olmos Pablo R. , Meneses Manuel , Borzone Gisella R.
Published: May 2018

Recurrent aspiration of gastric contents has been associated with several interstitial lung diseases. Despite this association, the pathogenic role of aspiration in these diseases has been poorly studied and little is known about extracellular matrix (ECM) changes in animal models of repetitive events of aspiration. Our aim was to study the repair phase of lung injury induced by each of several instillations of gastric fluid in Sprague-Dawley rats to evaluate changes in ECM and their reversibility. Anesthetized animals received weekly orotracheal instillations of gastric fluid for 1, 2, 3, and 4 wk and were euthanized at day 7 after last instillation. For reversibility studies, another group received 7 weekly instillations and was euthanized at day 7 or 60 after last instillation. Biochemical and histological measurements were used to evaluate ECM changes. Lung hydroxyproline content increased progressively and hematoxylin and eosin, Masson’s trichrome, and alpha-SMA stains showed that after a single instillation, intra-alveolar fibrosis predominated, whereas with repetitive instillations this fibrosis pattern became less prominent and interstitial fibrosis progressively became evident. Both type I and III collagen increased in intra-alveolar and interstitial fibrosis. Imbalance between matrix metalloproteinase-2 (MMP-2) activity and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was observed, favoring either collagen degradation or accumulation depending on the number of instillations. Caspase-3 activation was also dose dependent. ECM changes were partially reversible at long-term evaluation, since Masson bodies, granulomas, and foreign body giant cells disappeared, whereas interstitial collagen accumulated. In conclusion, repetitive lung instillations of gastric fluid induce progressive fibrotic changes in rat lung ECM that persist at long-term evaluation.
Reversing age-associated arterial dysfunction: insight from preclinical models
Authors: Gogulamudi Venkateswara R. , Cai Jinjin , Lesniewski Lisa A.
Published: May 2018

Cardiovascular diseases (CVDs) remain the leading causes of death in the United States, and advancing age is a primary risk factor. Impaired endothelium-dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase life span and improve age-related phenotypes, including arterial dysfunction. However, the translatability of long-term CR to clinical populations is limited, stimulating interest in the pursuit of pharmacological CR mimetics to reproduce the beneficial effects of CR. The energy-sensing pathways, mammalian target of rapamycin, AMPK, and sirtuin-1 have all been implicated in the beneficial effects of CR on longevity and/or physiological function and, as such, have emerged as potential targets for therapeutic intervention as CR mimetics. Although manipulation of each of these pathways has CR-like benefits on arterial function, the magnitude and/or mechanisms can be disparate from that of CR. Nevertheless, targeting these pathways in older individuals may provide some benefits against arterial dysfunction and CVD. The goal of this review is to provide a brief discussion of the mechanisms and pathways underlying age-associated dysfunction in large arteries, explain how these are impacted by CR, and to present the available evidence, suggesting that targets for energy-sensing pathways may act as vascular CR mimetics.
Time Delay Estimation of AIS Signal Based on Three‐Order Cumulant
Authors: Meng Xin , Zhao Dawei , Ma Shexiang , Teng Jianfu
Published: May 2018

A time delay estimation algorithm based on three‐order cumulant with the different symmetry of modulation signal between training sequence and information sequence of AIS (Automatic Identification System) is presented, which aims to overcome the large time delay and strong noise in the receiver side of AIS. Theoretical analysis and simulation results show that this algorithm successfully suppresses the influence of Gaussian noise. Moreover, under non‐Gaussian and correlative noise, it can also obtain a fine estimated performance. Simulation results show that this algorithm is superior to the correlative and data‐aided time delay estimation ones.
A Robot SLAM Improved by Quantum-Behaved Particles Swarm Optimization
Authors: Zuo Tao , Min Huasong , Tang Quan , Tao Qiang
Published: May 2018

We propose a new SLAM method based on fast simultaneous localization and mapping (FastSLAM). The technique presented uses an improved quantum-behaved particles swarm optimization (QPSO) to improve the proposal distribution of particles and optimize the estimated particles. This method makes the sampled particles closer to the true pose of the robot and improves the estimation accuracy of robot poses and landmarks. In the QPSO algorithm, the Gaussian disturbance is added to increase the diversity of the particles. By using this technique the premature convergence of particles swarm is overcome. In the resample step, the threshold value is used to evaluate the particle diversity. When the particle diversity is below the threshold value, the linear optimization is used to produce new sample particles, which increases the particle diversity and eliminates the loss of diversity. Simulations and experiments show that the proposed approach improves the accuracy of SLAM. The accuracy of estimated poses and landmarks with the proposed method is better than that with the traditional SLAM method.
48-Week Outcome after Cessation of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patient and the Associated Factors with Relapse
Authors: Xu Wen-xiong , Zhang Qian , Zhu Xiang , Lin Chao-shuang , Chen You-ming , Deng Hong , Mei Yong-yu , Zhao Zhi-xin , Xie Dong-ying , Gao Zhi-liang , Xie Chan , Peng Liang
Published: May 2018

Background and Aims. We aimed to ascertain the feasibility and safety of NA cessation, the status of patients after cessation, and the predictive factors for relapse and subsequent retreatment. Methods. A total of 92 patients were enrolled in this prospective study. Patients were monitored every month for the first 3 months after cessation and every 3 months thereafter. Results. Sixty-two patients finished 48 weeks of follow-up. None died or developed liver failure, cirrhosis, or HCC. The 62 patients could be divided into 4 categories according to the 48-week clinical development of relapse. Virologic relapses occurred in 39 (62.9%) patients, with 72.7% occurring in the first 24 weeks in origin HBeAg positive patients and 82.4% in the first 12 weeks in origin HBeAg negative patients. Age (OR = 1.06, 95% CI = 1.02–1.10; p=0.003), the HBsAg level (OR = 2.21, 95% CI = 1.47–3.32; p<0.001), and positive origin HBeAg status (OR = 0.32, 95% CI = 0.14–0.74; p=0.008) were predictive factors to virologic relapse. HBV DNA level (OR = 1.34, 95% CI = 1.13–1.58; p<0.001) was predictive factor to retreatment. Conclusions. NA cessation is safe under supervision. Age, HBsAg level, and origin HBeAg status can be predictive factors for virologic relapse. The study was submitted to ClinicalTrials.gov Protocol Registration and Results System with the assigned NCT ID NCT02883647.
Experimental Study of Thoracoabdominal Injuries Suffered from Caudocephalad Impacts Using Pigs
Authors: Guan Sishu , Liao Zhikang , Xiang Hongyi , Zhu Xiyan , Wang Zhong , Zhao Hui , Liu Peng , Lai Xinan
Published: May 2018

To know the caudocephalad impact- (CCI-) induced injuries more clearly, 21 adult minipigs, randomly divided into three groups: control group (n=3), group I (n=9), and group II (n=9), were used to perform the CCI experiments on a modified deceleration sled. Configured impact velocity was 0 m/s in the control group, 8 m/s in group I, and 11 m/s in group II. The kinematics and mechanical responses of the subjects were recorded and investigated. The functional change examination and the autopsies were carried out, with which the injuries were evaluated from the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS). The subjects in group I and group II experienced the caudocephalad loading at the peak pelvic accelerations of 108.92 ± 58.87 g and 139.13 g ± 78.54 g, with the peak abdomen pressures, 41.24 ± 16.89 kPa and 63.61 ± 65.83 kPa, respectively. The injuries of the spleen, lung, heart, and spine were detected frequently among the tested subjects. The maximal AIS (MAIS) of chest injuries was 4 in group I and 5 in group II, while both the MAIS of abdomen injuries in group I and group II were 5. The ISS in group II was 52.71 ± 6.13, significantly higher than in group I, 26.67 ± 5.02 (p<0.05). The thoracoabdomen CCI injuries and the mechanical response addressed presently may be useful to conduct both the prevention studies against military or civilian injuries.