bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired Nisin Resistance in
Staphylococcus aureus
Involves Constitutive Activation of an Intrinsic Peptide Antibiotic Detoxification Module
Authors: Randall Christopher P. , Gupta Arya , Utley-Drew Bret , Lee Siu Yi , Morrison-Williams Genevieve , O’Neill Alex J.
Published: December 2018

NIS and related bacteriocins are of interest as candidates for the treatment of human infections caused by Gram-positive pathogens such as
Staphylococcus aureus
. An important liability of NIS in this regard is the ease with which
S. aureus
acquires resistance. Here we establish that this organism naturally possesses the cellular machinery to detoxify NIS but that the ABC transporter responsible (VraDE) is not ordinarily produced to a degree sufficient to yield substantial resistance. Acquired NIS resistance mutations prompt activation of the regulatory circuit controlling expression of
vraDE
, thereby unmasking an intrinsic resistance determinant. Our results provide new insights into the complex mechanism by which expression of
vraDE
is regulated and suggest that a potential route to overcoming the resistance liability of NIS could involve chemical modification of the molecule to prevent its recognition by the VraDE transporter.
Growth hormone prescribing patterns in the UK, 2013–2016
Authors: Shepherd Sheila , Saraff Vrinda , Shaw Nick , Banerjee Indraneel , Patel Leena
Published: December 2018

Introduction

Prescribing of recombinant human growth hormone (rhGH) for growth failure in UK children is based on guidance from the National Institute for Health and Care Excellence. In 2013, the British Society for Paediatric Endocrinology and Diabetes initiated a national audit of newly prescribed rhGH treatment for children and adolescents. In this review, we have examined prescribing practices between 2013 and 2016.

Methods

All patients ≤16.0 years of age starting rhGH for licensed and unlicensed conditions in the UK were included. Anonymised data on indication and patient demographics were analysed.

Results

During the 4 years, 3757 patients from 76 of 85 (89%) centres started rhGH. For each licensed indication, proportions remained stable over this period: 56% growth hormone deficiency (GHD), 17% small for gestational age (SGA), 10% Turner syndrome, 6% Prader-Willi syndrome (PWS), 3% chronic renal insufficiency (CRI) and 2% short stature homeobox deficiency (SHOXd). However, the unlicensed category decreased from 10% (n=94) in 2013 to 5% (n=50) in 2016. The median age of patients starting rhGH was 7.6 years (range 0.1–16.0). Patients with PWS were significantly younger (median 2.2 years, range 0.2–15.1) compared with other indications (p<0.0001) and were followed by the SGA group (median 6.2 years, range 1.3–15.6, p<0.0001). Boys predominated in all groups except for PWS and SHOXd.

Conclusion

We demonstrate significant engagement of prescribing centres in this audit and a decline in unlicensed prescribing by half in this 4-year period. Patients in the PWS group were younger at initiation of rhGH compared with other indications and had no male predominance unlike GHD, SGA and CRI.
Splenectomy for breast carcinoma diffusely metastatic to the spleen presenting as severe transfusion-dependent anaemia and thrombocytopaenia
Authors: Hasadia Rabea , Kazarin Olga , Sofer Orit , Shulman Katerina , Troitsa Anton , Alfici Ricardo , Ashkenazi Itamar
Published: December 2018

We report a 48-year-old woman with metastatic infiltrating lobular carcinoma of the breast. Though her metastatic disease remained stable, she was repeatedly admitted for symptomatic anaemia and treated by red blood cell and platelet transfusions with increasing frequency as time elapsed. Abdominal examination and ultrasound revealed splenomegaly (27 cm span). A bone marrow biopsy showed fibrosis and foci of metastatic carcinoma. Splenectomy ameliorated her transfusion-dependent anaemia and thrombocytopaenia. Histopathology revealed multiple foci of metastatic carcinoma and scattered foci of extramedullary haematopoiesis. Differential diagnosis of anaemia and thrombocytopaenia in patients with cancer include bone morrow involvement by cancer cells, iron-deficiency anaemia, microangiopathies and chemotherapy suppression of haematopoiesis. Splenic involvement with cancer is common in patients with multivisceral disease. Many may regard transfusion-dependent severe anaemia and thrombocytopaenia as an end-stage disease in these patients. Nevertheless, palliative splenectomy should be considered in patients with possible hypersplenism who will otherwise survive for a relatively prolonged period of time.
Complication of dislodged gastrostomy Foley catheter: antegrade migration into small bowel
Authors: Cmorej Peter , Barbat Selwan , Sugawa Choichi
Published: December 2018

A 65-year-old man with dysphagia underwent placement of a percutaneous endoscopic gastrostomy tube. He was cared for at a nursing facility where the tube became dislodged and was replaced with similar size Foley catheter. Patient was brought to the hospital with dislodged feeding Foley but none was found at the bedside. Diagnostic workup revealed antegrade migration of the catheter into the small bowel. Push enteroscopy was unsuccessful in retrieving the catheter because it was too far distal. Patient was observed for a total of 7 days. Due to lack of progress with conservative measures, a colonoscopy was performed to extract the catheter, thus avoiding the need for more invasive surgical measures. If a Foley catheter is used as a gastrostomy tube, it should be replaced with a dedicated feeding tube as quickly as possible and should always be affixed to the skin to prevent antegrade migration and associated complications.
Effects of food items and related nutrients on metabolic syndrome using Bayesian multilevel modelling using the Tehran Lipid and Glucose Study (TLGS): a cohort study
Authors: Cheraghi Zahra , Nedjat Saharnaz , Mirmiran Parvin , Moslehi Nazanin , Mansournia Nasrin , Etminan Mahyar , Mansournia Mohammad Ali , McCandless Lawrence C
Published: December 2018

Objectives

Diet and nutrition might play an important role in the aetiology of metabolic syndrome (MetS). Most studies that examine the effects of food intake on MetS have used conventional statistical analyses which usually investigate only a limited number of food items and are subject to sparse data bias. This study was undertaken with the goal of investigating the concurrent effect of numerous food items and related nutrients on the incidence of MetS using Bayesian multilevel modelling which can control for sparse data bias.

Design

Prospective cohort study.

Setting

This prospective study was a subcohort of the Tehran Lipid and Glucose Study. We analysed dietary intake as well as pertinent covariates for cohort members in the fourth (2008–2011) and fifth (2011–2014) follow-up examinations. We fitted Bayesian multilevel model and compared the results with two logistic regression models: (1) full model which included all variables and (2) reduced model through backward selection of dietary variables.

Participants

3616 healthy Iranian adults, aged ≥20 years.

Primary and secondary outcome measures

Incident cases of MetS.

Results

Bayesian multilevel approach produced results that were more precise and biologically plausible compared with conventional logistic regression models. The OR and 95% confidence limits for the effects of the four foods comparing the Bayesian multilevel with the full conventional model were as follows: (1) noodle soup (1.20 (0.67 to 2.14) vs 1.91 (0.65 to 5.64)), (2) beans (0.96 (0.5 to 1.85) vs 0.55 (0.03 to 11.41)), (3) turnip (1.23 (0.68 to 2.23) vs 2.48 (0.82 to 7.52)) and (4) eggplant (1.01 (0.51 to 2.00) vs 1 09 396 (0.152×10–6to 768×1012)). For most food items, the Bayesian multilevel analysis gave narrower confidence limits than both logistic regression models, and hence provided the highest precision.

Conclusions

This study demonstrates that conventional regression methods do not perform well and might even be biased when assessing highly correlated exposures such as food items in dietary epidemiological studies. Despite the complexity of the Bayesian multilevel models and their inherent assumptions, this approach performs superior to conventional statistical models in studies that examine multiple nutritional exposures that are highly correlated.
Feasibility and validity of the Health Status Classification System-Preschool (HSCS-PS) in a large community sample: the Generation R study
Authors: Fang Xinye , Bai Guannan , Windhorst Dafna A , Feeny David , Saigal Saroj , Duijts Liesbeth , Jaddoe Vincent W V , Hu Shanlian , Jin Chunlin , Raat Hein
Published: December 2018

Objectives

To evaluate the feasibility, discriminant validity and concurrent validity of the Health Status Classification System-Preschool (HSCS-PS) in children aged 3 years in a large community sample in the Netherlands.

Design/setting

A prospective population-based cohort in Rotterdam, the Netherlands.

Participants

A questionnaire was administrated to a sample of parents of 4546 children (36.7±1.5 months).

Outcome measures

Health-related quality of life (HRQOL) of children was measured by HSCS-PS. The HSCS-PS consists of 10 original domains. Two single-item measures of ‘General health’ and ‘Behavior’ were added. A disability score was calculated by summing up all 10 original domains to describe the overall health status. Feasibility was assessed by the response rate, percentages of missing answers, score distributions and the presence of floor/ceiling effects. Discriminant validity was analysed between subgroups with predefined conditions: low birth weight, preterm birth, wheezing, Ear-Nose-Throat surgical procedures and behaviour problems. In the absence of another HRQOL measure, this study uses the single-items ‘General health’ and ‘Behavior’ as a first step to evaluate concurrent validity of the HSCS-PS.

Results

Feasibility: response rate was 69%. Ceiling effects were observed in all domains. Discriminant validity: the disability score discriminated clearly between subgroups of children born with a ‘very low birth weight’, ‘very preterm birth’, with ‘four or more than four times wheezing’, ‘at least one ear-nose-throat surgical procedures’, ‘behaviour problems present’ and the ‘reference’ group. Concurrent validity: HSCS-PS domains correlated better with hypothesised parallel additional domains than with other non-hypothesised original domains.

Conclusions

This study supports the feasibility and validity of the HSCS-PS among preschoolers in community settings. We recommend developing a utility-based scoring algorithm for the HSCS-PS. Further empirical studies and repeated evaluations in varied populations are recommended.
Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial
Authors: Kearney Rebecca Samantha , McKeown Rebecca , Stevens Siobhan , Parsons Nicholas , Parsons Helen , Wells Philip , Brown Jaclyn , Underwood Martin , Redmond Anthony , Mason James , Costa Matthew L
Published: December 2018

Introduction

Each year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture.

Methods and analysis

We will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case.

Ethics, registration and dissemination

National Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice.

Trial registration number

ISRCTN15537280; Pre-results.
Increased plasma leptin as a novel predictor for psychopathological depressive symptoms in chronic schizophrenia
Authors: Xu Jinjie , Jiao Yumei , Xing Mengjuan , Lin Yezhe , Su Yousong , Ding Wenhua , Zhu Cuizhen , Peng Yanmin , Qi Dake , Cui Donghong
Published: December 2018

Background

Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.

ObjectiveAims

To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.

Methods

Cross-sectional studies were applied to (1) compare the levels of plasma leptin between schizophrenia (n=74) and healthy controls (n=50); and (2) investigate the relationship between plasma leptin levels and depressive subscores.

Results

(1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls. (2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale (PANSS). (3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.

Conclusion

Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.
Beam hardening artifacts of liquid embolic agents: comparison between Squid and Onyx
Authors: Pop Raoul , Mertz Luc , Ilyes Annamaria , Mihoc Dan , Richter Johann Sebastian , Manisor Monica , Kremer Stéphane , Beaujeux Rémy
Published: December 2018

Background

Initial clinical experience with Squid shows subjectively reduced artifacts on post-embolization CT scans compared with Onyx. To further investigate these observations, we aimed to perform a comparison of artifacts between Squid and Onyx in a controlled in vitro model.

Materials and methods

Onyx 18 and all four variants of Squid (Squid 18, Squid 18 low density (LD), Squid 12, Squid 12 LD) were each injected in dimethylsulfoxide (DMSO) compatible test tubes. The tubes containing precipitated embolic material were inserted in a CT phantom for conventional and flat panel CT acquisitions. Beam hardening artifacts were quantified using objective and subjective measurements.

Results

Objective evaluation of artifacts within regions of interest (ROIs) placed around the embolic material on CT and flat panel CT images demonstrated significantly lower noise and Hounsfield unit (HU) range values for all four Squid products compared with Onyx 18. On both CT and flat panel CT, LD variants of Squid 18 and Squid 12 had significantly lower noise and HU range values than their normal density counterparts on longitudinal ROIs. When using subjective measures for diagnostic value within ROIs placed around the embolic material on both CT and flat panel CT images, the number of non-diagnostic ROIs was significantly higher for Onyx 18 than for all four Squid variants.

Conclusion

All four variants of Squid induced fewer beam hardening artifacts than Onyx 18 on CT and flat panel CT acquisitions. LD variants of Squid induced fewer artifacts than their normal density counterparts.
Performance prediction of construction projects using soft computing methods
Authors: Fanaei Seyedeh Sara , Moselhi Osama , Alkass Sabah T.
Published: December 2018

Key performance indicators (KPIs) evaluate different aspects of projects and are used to determine the health status of projects. While there is considerable work on project quantitative performance prediction, less attention, however, has been directed towards qualitative performance prediction. This paper offers a novel framework for qualitatively measuring and predicting six important construction project KPIs using the neuro-fuzzy technique. Neuro-fuzzy models are developed to map the KPIs of three critical project stages to whole project KPIs. Subtractive clustering is utilized to automatically generate initial fuzzy inference system (FIS) models and the artificial neural network (ANN) technique is used to tune the parameters of the initial FIS models. The relative weight of each KPI is determined using a series of computing methods namely, analytic hierarchy process (AHP) and genetic algorithm (GA), to generate the performance indicator (PI). The developed models are validated with real project data showing that the rate of error is reasonably low. The results show that the AHP method is more accurate when compared to the GA method. This framework can be used in building construction projects to help decision-makers evaluate the performance of their projects.
AAC Carver field pea
Authors: Bing Deng-Jin , Beauchesne Don , McLaren Debra , Gan Yantai , Cuthbert Richard
Published: December 2018

AAC Carver is a semi-leafless, yellow cotyledon, high-yielding field pea (Pisum sativum L.) variety developed at the Lacombe Research and Development Centre, Agriculture and Agri-Food Canada, Lacombe, AB, Canada. It has a maturity of 96 d, seed size of 226 g, and good lodging resistance. AAC Carver is resistant to powdery mildew (caused by Erysiphe pisi DC.), and moderately susceptible to mycosphaerella blight [caused by Mycosphaerella pinodes (Berk. & Bloxam.) Vestergr.] and fusarium wilt [caused by Fusarium oxysporum f. pisi (Linford) Snyd. & Hans.]. AAC Carver is adapted to all field growing regions in western Canada.
Demographics and social values as drivers of change in the Canadian boreal zone1
Authors: Nitoslawski Sophie A. , Chin Andrew T.M. , Chan Alistair , Creed Irena F. , Fyles James W. , Parkins John R. , Weber Marian L.
Published: December 2018

The boreal zone, a vast region with abundant natural resources and related industries, has both provisioning and nonprovisioning ecosystem services that draw some people, while warding off others. It is an area that arguably affects many Canadians in different ways and represents a wide range of tangible and intangible values. Changes in demographic patterns over time shed light on the development of the social-ecological landscape of the boreal zone, and elucidate potential changes in the future. Using past and current demographic data, we explore population size, immigration and emigration, and birth and death rates within and outside the boreal zone. We also explore links between demographics, social values, and important factors of change in the boreal zone, and present three contrasting scenarios predicting the state of this zone in 2050. We pay particular attention to the Indigenous population, generational differences, international immigration, and the urban–rural divide. Fertility rates and immigration influence population demographics within and outside the boreal zone, respectively, alluding to potential divergences in social values and between communities located within and outside the boreal zone. The boreal zone is currently comprised of many smaller towns and communities scattered across the landscape, yet it is equally important to consider the influences of larger cities located outside the boreal zone, particularly in terms of governance, population movements, and political power. Considered together, these factors provide insight on social cohesion and connectedness, demand for goods and services, and changes in boreal-centric activities.
Effect of alpha particle irradiations on the structural properties of graphene oxide
Authors: Eissa M. F. , El Rouby Waleed M. A.
Published: December 2018

Graphene has been considered one of the most important materials for many applications due to its unique electronic structure, physical and chemical properties. Graphite flakes are the main source of graphene oxide which can be transformed to graphene after reduction. The effect of irradiation on graphene oxide has been rarely studied, only few studies dealing with the irradiation of graphene oxide with gamma radiation were reported. The effect of irradiation of graphene oxide with gamma ray doses (low linear energy transfer) has been previously studied. It was found that there are no changes in the crystalline structure of graphene oxide after irradiation. Graphene oxide was prepared by modified Hummer’s method. The scanning electron microscopy image of the obtained sample suggests the presence of both single and multilayer graphene oxide sheets. The structural measurements for the graphene oxide samples with high linear energy transfers were carried out after irradiations with different doses of alpha particle (9.30–479.90 Gy). The effect of irradiation on oxygen functional groups of graphene oxide was followed by Fourier transforms infra-red spectrometer. Moreover, the irradiation effect on the lamellar space of graphene oxide layers was measured by X-ray diffraction. It was found that the d-spacing of graphene oxide was decreased after alpha particles irradiation with different doses. The effect of irradiation on dielectric constant and conductivity of graphene oxide samples was measured in the frequency range (200 Hz–1.00 MHz). The dielectric measurements show less dependence on irradiation doses. The graphene oxide sample can be used as radiation dosimeter for [Formula: see text]-particles in the range of the low irradiation doses.
Stochastic transitions in the Schlögl reaction model with nonextensive statistical noise and Gaussian white noise
Authors: Guo Peirong , Xu Wei , Wang Haiyan , Mei Ruoxing
Published: December 2018

In this paper, we investigate the stochastic transitions in a bistable Schlögl chemical reaction subjected to a nonextensive statistical noise (NESN) and a Gaussian white noise. The NESN is a correlated noise, and able to describe heavy-tailed noise distributions with certain deviation degree relative to Gaussian colored noise. With a unified-colored noise approximation method, the theoretical results of the steady state probability density function (PDF) and mean first passage time (MFPT) are obtained to demonstrate the influences of NESN. The validity of theoretical results has been confirmed by numerical simulations of the PDFs. Besides, stochastic P-bifurcation is discovered based on the changing of PDFs. The results show that the NESN will keep the conversion rate of substrate and the generation rate of products in the low state. Finally, from the MFPT, we find that the intensity and deviation degree of NESN, and Gaussian noise intensity can decrease the switching time between two states.
Influence of peak current on substrate plasma sheath properties of Ti films deposited by high-power pulsed magnetron sputtering
Authors: Chen C. Z. , Ma D. L. , Huang N. , Leng Y. X.
Published: December 2018

For film deposition, the substrate sheath properties, such as the plasma density, ion-to-atom ratios around the substrate, are more important for the film structure. In this paper, titanium thin films were deposited on grounded substrates by high-power pulsed magnetron sputtering (HPPMS) with the peak current in the range of 113–185 A. A simple and new equivalent circuit model of the sheath was established to study the plasma density around the substrate sheath. The Ti ion-to-atom ratios near substrate were studied by optical emission spectroscopy (OES), and the film structure was detected by transmission electron microscopy (TEM). The results showed that the calculated plasma density was from 0.8 × 10[Formula: see text] to 1.4 × 10[Formula: see text] m[Formula: see text] at different peak current. These were consistent with the results measured by a modified one-grid ion collector using saturation current probe method, which proved our proposed equivalent circuit model was correct. The Ti ion-to-atom ratios around the substrate were estimated at about 24%–62%. The plasma density and ion to atom ratio around the substrate increased with the peak current, and this could lead to a higher film crystallization and preference growth on Ti (101) and (100).
The mechanistic effect over the substrate in a square type atomic layer deposition reactor
Authors: Coetzee Rigardt Alfred Maarten , Jen Tien-Chien , Bhamjee Muaaz , Lu Junling
Published: December 2018

The attractive key-enabling nanotechnology manufacturing technique of atomic layer deposition (ALD) is well-known to deposit ultra-thin, uniform, conformal and pinhole-free nano-films on complex topography. Over the years it has been used to deposit ultra-thin films in a multitude of industry applications such as microelectronics, solar cells, superconductors, fuel cells, and water purification membranes, among other applications. This study investigates the ALD process effects in the fabrication of Al2O3 thin film over the substrate. The mass fraction coverage over the substrate and deposition rate contours in a Gemstar 6 ALD reactor are examined. The analysis technique illustrates the parameter behavior over a Cartesian coordinate sector in a three-dimensional illustration. The governing laws of the conservation of mass, momentum, energy, species, and kinetic chemical reactions are analyzed numerically by ANSYS Fluent and ChemkinPro. The deposition rate profiles correlated with previous experimental findings in the literature, producing an average growth rate of 1.3 Å/cycles.
Error Analysis and Compensation in Images Stitching for the Mechanically Stitched CCD Aerial Cameras
Authors: Kuang Haipeng , Zheng Lina , Yuan Guoqin , Sun Jianjun , Zhang Zhuang
Published: December 2018

Image misalignment during image stitching is a common issue for the mechanically stitched CCDs in the aerial cameras due to the relative image motion between CCDs. In this paper, we analyze the error in imaging stitching for the mechanically stitched CCDs and propose a compensation method based on position and orientation system (POS). First, the imaging relationship of overlapping pixels in mechanical stitching is analyzed. The imaging model of adjacent CCD is constructed according to the collinear equation. The effects of stitching staggered distance, carrier attitude change and flight speed on the image mosaic of overlapping areas are given. Monte Carlo algorithm is used to analyze the statistical value of image mosaic error in overlapping area under typical working conditions. Then, a geometric correction method based on POS recording of external orientation elements of adjacent CCD imaging is proposed. The overlapping area stitching error is reduced from 14.9 pixels to 0.4 pixels which meets the engineering requirements. The mechanical stitching mathematical model, analysis and correction method established in this paper have strong engineering and application significance for mechanical stitching of aerial cameras.
Looking Under the Hood of Z-Wave
Authors: Badenhop C. W. , Graham S. R. , Mullins B. E. , Mailloux L. O.
Published: December 2018

Z-Wave is a proprietary Internet of Things substrate providing distributed home and office automation services. The proprietary nature of Z-Wave devices makes it difficult to determine their security aptitude. While there are a variety of open source tools for analyzing Z-Wave frames, inspecting non-volatile memory, and disassembling firmware, there are no dynamic analysis tools allowing one to inspect the internal state of a Z-Wave transceiver while it is running. In this work, a memory introspection capability is developed for three Z-Wave devices containing a ZW0301, a Z-Wave transceiver system-on-chip. In all three devices, the firmware image is modified to include the memory introspection capability by hooking an existing data exfiltration mechanism used by the device. The memory introspection capability is applied to determine how nonces are generated by Z-Wave devices to prevent replay attacks. Through a combination of static and dynamic analysis, the nonce generating algorithm is found to be based on a nonce round key that updates every secure frame transaction.
Properties of single-channel and whole cell Cl− currents in guinea pig detrusor smooth muscle cells
Authors: Yarotskyy Viktor , Malysz John , Petkov Georgi V.
Published: December 2018

Multiple types of Cl− channels regulate smooth muscle excitability and contractility in vascular, gastrointestinal, and airway smooth muscle cells. However, little is known about Cl− channels in detrusor smooth muscle (DSM) cells. Here, we used inside-out single channel and whole cell patch-clamp recordings for detailed biophysical and pharmacological characterizations of Cl− channels in freshly isolated guinea pig DSM cells. The recorded single Cl− channels displayed unique gating with multiple subconductive states, a fully opened single-channel conductance of 164 pS, and a reversal potential of −41.5 mV, which is close to the ECl of −65 mV, confirming preferential permeability to Cl−. The Cl− channel demonstrated strong voltage dependence of activation (half-maximum of mean open probability, V0.5, ~−20 mV) and robust prolonged openings at depolarizing voltages. The channel displayed similar gating when exposed intracellularly to solutions containing Ca2+-free or 1 mM Ca2+. In whole cell patch-clamp recordings, macroscopic current demonstrated outward rectification, inhibitions by 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS) and niflumic acid, and insensitivity to chlorotoxin. The outward current was reversibly reduced by 94% replacement of extracellular Cl− with I−, Br−, or methanesulfonate (MsO−), resulting in anionic permeability sequence: Cl−>Br−>I−>MsO−. While intracellular Ca2+ levels (0, 300 nM, and 1 mM) did not affect the amplitude of Cl− current and outward rectification, high Ca2+ slowed voltage-step current activation at depolarizing voltages. In conclusion, our data reveal for the first time the presence of a Ca2+-independent DIDS and niflumic acid-sensitive, voltage-dependent Cl− channel in the plasma membrane of DSM cells. This channel may be a key regulator of DSM excitability.
Indirect, referent control of motor actions underlies directional tuning of neurons
Authors: Feldman Anatol G.
Published: December 2018

Many neurons of the primary motor cortex (M1) are maximally sensitive to “preferred” hand movement directions and generate progressively less activity with movements away from these directions. M1 activity also correlates with other biomechanical variables. These findings are predominantly interpreted in a framework in which the brain preprograms and directly specifies the desired motor outcome. This approach is inconsistent with the empirically derived equilibrium-point hypothesis, in which the brain can control motor actions only indirectly, by changing neurophysiological parameters that may influence, but remain independent of, biomechanical variables. The controversy is resolved on the basis of experimental findings and theoretical analysis of how sensory and central influences are integrated in the presence of the fundamental nonlinearity of neurons: electrical thresholds. In the presence of sensory inputs, electrical thresholds are converted into spatial thresholds that predetermine the position of the body segments at which muscles begin to be activated. Such thresholds may be considered as referent points of respective spatial frames of reference (FRs) in which neurons, including motoneurons, are centrally predetermined to work. By shifting the referent points of respective FRs, the brain elicits intentional actions. Pure involuntary reactions to perturbations are accomplished in motionless FRs. Neurons are primarily sensitive to shifts in referent directions, i.e., shifts in spatial FRs, whereas emergent neural activity may or may not correlate with different biomechanical variables depending on the motor task and external conditions. Indirect, referent control of posture and movement symbolizes a departure from conventional views based on direct preprogramming of the motor outcome.
The primacy of rhythm: how discrete actions merge into a stable rhythmic pattern
Authors: Zhang Zhaoran , Sternad Dagmar
Published: December 2018

This study examined how humans spontaneously merge a sequence of discrete actions into a rhythmic pattern, even when periodicity is not required. Two experiments used a virtual throwing task, in which subjects performed a long sequence of discrete throwing movements, aiming to hit a virtual target. In experiment 1, subjects performed the task for 11 sessions. Although there was no instruction to perform rhythmically, the variability of the interthrow intervals decreased to a level comparable to that of synchronizing with a metronome; furthermore, dwell times shortened or even disappeared with practice. Floquet multipliers and decreasing variability of the arm trajectories estimated in state space indicated an increasing degree of dynamic stability. Subjects who achieved a higher level of periodicity and stability also displayed higher accuracy in the throwing task. To directly test whether rhythmicity affected performance, experiment 2 disrupted the evolving continuity and periodicity by enforcing a pause between successive throws. This discrete group performed significantly worse and with higher variability in their arm trajectories than the self-paced group. These findings are discussed in the context of previous neuroimaging results showing that rhythmic movements involve significantly fewer cortical and subcortical activations than discrete movements and therefore may pose a computationally more parsimonious solution. Such emerging stable rhythms in neuromotor subsystems may serve as building blocks or dynamic primitives for complex actions. The tendency for humans to spontaneously fall into a rhythm in voluntary movements is consistent with the ubiquity of rhythms at all levels of the physiological system.

NEW & NOTEWORTHY When performing a series of throws to hit a target, humans spontaneously merged successive actions into a continuous approximately periodic pattern. The degree of rhythmicity and stability correlated with hitting accuracy. Enforcing irregular pauses between throws to disrupt the rhythm deteriorated performance. Stable rhythmic patterns may simplify control of movement and serve as dynamic primitives for more complex actions. This observation reveals that biological systems tend to exhibit rhythmic behavior consistent with a plethora of physiological processes.
Intermittent single-joint fatiguing exercise reduces TMS-EEG measures of cortical inhibition
Authors: Otieno Lavender A. , Opie George M. , Semmler John G. , Ridding Michael C. , Sidhu Simranjit K.
Published: December 2018

Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with peripherally recorded motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS). Combined TMS and electroencephalography (TMS-EEG) allows for more direct recording of cortical responses through the TMS-evoked potential (TEP). The aim of this study was to investigate the changes in the excitatory and inhibitory components of the TEP during fatiguing single-joint exercise. Twenty-three young (22 ± 2 yr) healthy subjects performed intermittent 30-s maximum voluntary contractions of the right first dorsal interosseous muscle, followed by a 30-s relaxation period repeated for a total of 15 min. Six single-pulse TMSs and one peripheral nerve stimulation (PNS) to evoke maximal M wave (Mmax) were applied during each relaxation period. A total of 90 TMS pulses and 5 PNSs were applied before and after fatiguing exercise to record MEP and TEP. The amplitude of the MEP (normalized to Mmax) increased during fatiguing exercise ( P < 0.001). There were no changes in local and global P30, N45, and P180 of TEPs during the development of intermittent single-joint exercise-induced fatigue. Global analysis, however, revealed a decrease in N100 peak of the TEP during fatiguing exercise compared with before fatiguing exercise ( P = 0.02). The decrease in N100 suggests a fatigue-related decrease in global intracortical GABAB-mediated inhibition. The increase in corticospinal excitability typically observed during single-joint fatiguing exercise may be mediated by a global decrease in intracortical inhibition.

NEW & NOTEWORTHY Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with transcranial magnetic stimulation (TMS)-evoked potentials from the muscle. The present study provides new and direct cortical evidence, using TMS-EEG to demonstrate that during single-joint fatiguing exercise there is a global decrease in intracortical GABAB-mediated inhibition.
Innate Immune Signaling and Its Role in Metabolic and Cardiovascular Diseases
Authors: Xu Meng , Liu Peter P. , Li Hongliang
Published: December 2018

The innate immune system is an evolutionarily conserved system that senses and defends against infection and irritation. Innate immune signaling is a complex cascade that quickly recognizes infectious threats through multiple germline-encoded cell surface or cytoplasmic receptors and transmits signals for the deployment of proper countermeasures through adaptors, kinases, and transcription factors, resulting in the production of cytokines. As the first response of the innate immune system to pathogenic signals, inflammatory responses must be rapid and specific to establish a physical barrier against the spread of infection and must subsequently be terminated once the pathogens have been cleared. Long-lasting and low-grade chronic inflammation is a distinguishing feature of type 2 diabetes and cardiovascular diseases, which are currently major public health problems. Cardiometabolic stress-induced inflammatory responses activate innate immune signaling, which directly contributes to the development of cardiometabolic diseases. Additionally, although the innate immune elements are highly conserved in higher-order jawed vertebrates, lower-grade jawless vertebrates lack several transcription factors and inflammatory cytokine genes downstream of the Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) pathways, suggesting that innate immune signaling components may additionally function in an immune-independent way. Notably, recent studies from our group and others have revealed that innate immune signaling can function as a vital regulator of cardiometabolic homeostasis independent of its immune function. Therefore, further investigation of innate immune signaling in cardiometabolic systems may facilitate the discovery of new strategies to manage the initiation and progression of cardiometabolic disorders, leading to better treatments for these diseases. In this review, we summarize the current progress in innate immune signaling studies and the regulatory function of innate immunity in cardiometabolic diseases. Notably, we highlight the immune-independent effects of innate immune signaling components on the development of cardiometabolic disorders.
Anomalous Origin of a Right Coronary Artery from Pulmonary Artery
Authors: Rawala Muhammad Shabbir , Naqvi S. Tahira Shah , Farhan Kinaan , Yasin Muhammad , Rizvi Syed Bilal
Published: December 2018

Congenital defects of the coronary arteries are noted in 0.2–1.4% of the general population. The first case of an anomalous origin of right coronary artery from pulmonary artery (ARCAPA) was described by Brooks in 1885. ARCAPA has an overall incidence of 0.002% in the general population. Most of the cases are asymptomatic; however, it can lead to serious complications such as heart failure, ischemia, and sudden death. A 57-year-old man presented to the cardiologist’s office with complaints of shortness of breath and fatigue. The patient also had a previous history of coronary stents and heart failure. Initially, he was evaluated with a stress test which was reported as abnormal. The patient then underwent an invasive coronary angiography that revealed anomalous origin of the right coronary artery (RCA) and multivessel disease. Cardiothoracic surgery evaluated the patient and coronary artery bypass graft was performed. During the surgery, the anomalous origin of RCA from the pulmonary artery was identified and was successfully corrected by reimplanting the RCA into the ascending aorta. The anomalous origin of RCA is a rare yet life-threatening condition. The RCA due to its location of origin from the pulmonary artery tends to be a low-pressure vessel with a very thin and fragile wall. It also serves as a retrograde venous conduit from the left coronary circulation into the pulmonary artery. This connection results in a left-to-right shunt that explains the increase in oxygen saturation in the pulmonary artery and the high cardiac output which is normally seen in these cases. The clinical presentation can vary from coronary ischemia to heart failure or sudden death. Therefore, surgical correction is recommended even in asymptomatic patients. We present a case of an anomalous origin of RCA from the pulmonary artery which, unlike the origin of left coronary from pulmonary artery, is very rare. Patients with this condition should have early correction even if they are asymptomatic in order to prevent long-term complications.
Drug-Drug Interaction of Ergotamine with a Combination of Darunavir, Abacavir, and Lamivudine Causing a Fatal Vasospastic Ischemia
Authors: Petit Elisabeth , Schoonheydt Karen , Meert Philippe , Van Laer Marie
Published: December 2018

Ergotamine toxicity has become a rare condition which can be caused by, among others, drug-drug interaction. In this work we report a case with vasospastic ischemia induced by the wrongful combination of ergotamine with recently started Antiretroviral Therapy. Clinicians were not aware that patient was self-medicating for years with medication containing ergotamine and caffeine for migraines. This diagnosis was established after evaluating the evolving ‘and spreading’ ischemia and CT scans and thoroughly interviewing patient’s family. Treatment was started with intravenous nimodipine and intra-arterial sodium nitroprusside on the affected limbs. The patient developed severe limb ischemia, cerebral ischemia, and metabolic encephalopathy. Unfortunately no improvements were noticeable and due to evolving cerebral edema as a result of the ischemia, the patient developed brain herniation and died shortly after.
Multicomponent Reactions, Solvent-Free Synthesis of 2-Amino-4-aryl-6-substituted Pyridine-3,5-dicarbonitrile Derivatives, and Corrosion Inhibitors Evaluation
Authors: Mahmoud Naglaa F. H. , El-Sewedy Ahmed
Published: December 2018

A number of 2-amino-4-aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives were synthesized via one-pot multicomponent condensation reactions of different aromatic aldehydes with malononitrile and different primary amines, using different molecular ratios and different reaction conditions to achieve considerable product yields. Moreover, we succeed, for the first time to develop a new method to synthesize the aforementioned under the fusion condition without using solvent and catalysts. With this method, a wide range of novel 2-amino-3,5-dicyano-4-aryl-6-substituted aminopyridine derivatives were synthesized with high yields and board substrate of functional groups. The synthesized pyridine derivatives were found to have a corrosion inhibition efficiency, the rate of which increased with the increasing concentration of the derivatives. The structures of the new compounds were elucidated by spectroscopic data and elemental analyses.
Comparative Study on the Axial Compression and Bearing Capacity of Reactive Powder Concrete‐Filled Circular Steel Tube
Authors: Chen Mingyang , Hou Xiaomeng
Published: December 2018

Reactive powder concrete (RPC) was confined by the circular steel tube to obtain the required ductility. The axial compression test results of 139 columns from different scholars were collated and compared to study the axial compression and bearing capacity of a reactive powder concrete‐filled circular steel tube, of which the confining coefficient is 0.057–2.312 and the RPC strength is 76.6–178.2 MPa. Load‐displacement curves have been categorized into four stages: (1) elastic; (2) elastic‐plastic; (3) descending; and (4) strengthening. The failure mode can be divided into three types according to the different confining coefficients as (1) wall buckling; (2) diagonal shear; and (3) drum‐shaped. The confining coefficient, core RPC strength, steel fiber volume, steel tube D/t ratio, and loading mode on the ultimate bearing capacity were analyzed. The results showed the confining coefficient to be the main factor affecting ultimate bearing capacity. The equation for determining ultimate bearing capacity was established based on the limit equilibrium theory, with the lateral confining coefficient of RPC (k) determined to be 2.86, less than that of normal concrete at 4.1. Based on the experimental analysis results and China’s “Design and Construction Code for Concrete‐Filled Steel Tube Structure” (CECS 28‐2012), the design proposal for an RPC‐filled steel tube was recommended.
Spatial Planning of Electric Vehicle Infrastructure for Belo Horizonte, Brazil
Authors: Costa Evaldo , Paiva Arthur , Seixas Julia , Costa Gustavo , Baptista Patrícia , Gallachóir Brian Ó.
Published: December 2018

In pursuit of a more sustainable transportation system, electric vehicles (EVs) have the potential to play a fundamental role due to their improved efficiency and lower emissions. The absence of an adequate electric vehicle supply equipment (EVSE) network has been one of the major obstacles for the mass adoption of EV, in large municipalities of developing countries. This is the case in Belo Horizonte (BH), Brazil, which also has a high motorization rate (7 light-duty vehicles per 10 inhabitants). The purpose of this study is to measure and identify the optimal locations for EVSE according to selected criteria to meet the needs of light-duty electric vehicles (LDEV) corresponding to a penetration of 1% by 2025 in the municipality of BH. The study highlights the most important attributes that need to be considered for the installation of an EVSE network in an urban space for a developing country. Multi-Criteria Decision Making (MCDM), the Weighted Linear Combination (WLC) method, and the Analytical Hierarchy Process (AHP) technique based on the inputs from a group of Brazilian electrical mobility specialists, coupled with a Geographic Information System (GIS) modeling tool, were used for this study. The results revealed that around 1,200 EVSE units are needed, with a large concentration of EVSE in a small region. We also illustrate where stakeholders should focus their attention for the successful promotion of EV. The development methodology has the potential to be applied in other future EVSE development projects.