bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of chronic hypoxia and hypercapnia on learning and memory function in mice and the expression of NT and CGRP in brain
Authors: Xu Hangyu , Xu Hao
Published: December 2018

The aim of this study is to investigate the effects of chronic hypoxia and hypercapnia on learning and memory function of mice and the expression of neurotensin (NT) and calcitonin gene–related peptide (CGRP) in mice brain. A total of 30 C57BL/6J male mice were randomly divided into normoxia control group (control group, n = 15) and chronic hypoxia and hypercapnia stress group (experimental group, n = 15). The control group was kept under normal temperature and pressure conditions, while the experimental group was kept in a chamber at normal pressure, hypoxia and hypercapnia for 8 h daily and 6 days a week for 4 weeks. On the 28th day, the learning and memory ability of mice was examined by 8-arm maze. The content of 8-hydroxy-deoxyguanosine (8-OHdG) in brain was detected by enzyme-linked immunosorbent assay (ELISA) analysis. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined by spectrophotometry, and the derangement of hippocampal ultrastructures and numbers of apoptotic neurons were observed by microscope. The expression of NT and CGRP in brain tissue was observed by immunochemistry. Compared to control group, the content of 8-OHdG in hippocampal and serum MDA were significantly increased by 1.3 and 1.78 times, while the activity of SOD in serum was decreased by 27.28% in experimental group. Besides, the cellular structure of the hippocampus was disorderly arranged, the shape is irregular and the quantity is markedly reduced obviously in experimental group. In addition, the content of NT and CGRP in brain tissue was higher in experimental group than in control group ( P < 0.05). The stress of chronic hypoxia and hypercapnia not only can induce learning and memory disorders in mice which may be related to increased neuronal apoptosis and oxidative stress injury but also can increase the expression of NT and CGRP in brain tissue which may have some impact on gastrointestinal motility in mice.
Therapeutic efficacy of liraglutide on diabetic nephropathy mice by inhibiting inflammatory factors
Authors: Fan WenXing , Liang Zhang , Xiao Hua , Yang QiuPing
Published: December 2018

This study was to investigate the role and mechanism of liraglutide in the treatment of diabetic nephropathy (DN) mice. A mouse model of streptozotocin-induced DN was established. The mice were intraperitoneally injected with liraglutide at a dose of 200 μg/kg for 6 weeks. The expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), and nuclear factor kappa B (NF-κB) messenger RNA (mRNA) in renal tissue of mice was examined by real-time quantitative polymerase chain reaction (PCR). Meanwhile, the expression of IL-6 and TNF protein in renal tissue of mice was detected by western blot, while the expression of NF-κB protein in renal tissues of each group was detected by immunofluorescence. After 6 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and weight of the liraglutide group were significantly lower than those of the DN group ( P < 0.01 or P < 0.05), whereas high-density lipoprotein (HDL) was significantly increased ( P < 0.05). At the same time, the microscale albuminuria (MAU) and N-acetyl-β-d-glucosaminidase (NAG) in the liraglutide group were significantly lower than those in the DN group ( P < 0.05). Moreover, the urea (UR), creatinine (CR), and uric acid (UA) in the liraglutide group were significantly lower than those in the DN group ( P < 0.01 or P < 0.05). In addition, the mRNA and proteins of IL-6, TNF, and NF-κB in the liraglutide group were significantly lower than those in the DN group ( P < 0.05). In conclusion, the mechanism of liraglutide in the treatment of DN may be related to the inhibition of the expression of genes and proteins of inflammatory factors.
“Loving Nursing” and “Taking Responsibility”: Strategies for Transitioning to Practice in Lebanon
Authors: Clinton Michael , Ezzeddine Sawsan , Doumit Myrna , Rizk Ursula , Madi Murielle
Published: December 2018

Transitioning to practice is challenging for baccalaureate nursing students. In baccalaureate nursing programs, the process typically begins in the junior year. A Successful transition depends on how well students apply their developing knowledge during clinical placements. A cross-sectional, multisite, qualitative study was conducted at four universities in Greater Beirut, Lebanon. In total, 35 junior baccalaureate students participated in audio-recorded focus group discussions. Thematic analysis was used to analyze the data. Three themes were sufficient to summarize the students experiences: “being unprepared,” “learning unexpected lessons,” and “taking responsibility.” Three subthemes, revising expectations, discovering divergence, and self-monitoring, were used to clarify the unexpected lessons students learned during clinical placements and how students responded. “Loving nursing and protecting yourself,” making the most of every day, and doubting future readiness were subthemes within the “taking responsibility” theme. Students troubled by nursing practices that diverged from their expectations monitored themselves to avoid falling into poor practices and kept track of the nursing procedures they performed. Only by taking responsibility for their learning, could students develop the competencies they will need as registered nurses. Faculty, clinical instructors, hospital administrators, nurse managers, and registered nurses need to do more to support students to take control of their learning.
Unique and Transdiagnostic Symptoms of Hypomania/Mania and Unipolar Depression
Authors: Stanton Kasey , Khoo Shereen , Watson David , Gruber June , Zimmerman Mark , Weinstock Lauren M.
Published: December 2018

Extensive research has been conducted to isolate features that distinguish bipolar spectrum disorders from unipolar depression. Therefore, we identified latent symptom dimensions that are unique versus shared across these disorders by examining the joint structure of hypomanic/manic and depressive symptoms in two large samples (i.e., 647 community adults; 1,370 outpatients with unipolar depression or bipolar disorder history). Results across studies suggested that (a) many hypomanic/manic and depressive symptoms (e.g., irritability) are transdiagnostic, but also that (b) symptoms such as increased energy and euphoric mood define a latent specific positive activation dimension that appears more specific to bipolar disorder. We discuss how these results indicate that some symptoms may be more optimal to target than others when trying to distinguish bipolar disorder from unipolar depression, as well as how the identification of relatively disorder-specific symptom types may optimally guide future research on key mechanisms linked to hypomania/mania and depression.
Fibronectin modulates formation of PF4/heparin complexes and is a potential factor for reducing risk of developing HIT
Authors: Krauel Krystin , Preuße Patricia , Warkentin Theodore E. , Trabhardt Catja , Brandt Sven , Jensch Inga , Mandelkow Martin , Hammer Elke , Hammerschmidt Sven , Greinacher Andreas
Published: December 2018

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating anti–platelet factor 4 (PF4)/heparin antibodies. Platelet activation assays that use “washed” platelets are more sensitive for detecting HIT antibodies than platelet-rich plasma (PRP)–based assays. Moreover, heparin-exposed patients vary considerably with respect to the risk of PF4/heparin immunization and, among antibody-positive patients, the risk of subsequent “breakthrough” of clinical HIT with manifestation of thrombocytopenia. We used washed platelets and PRP, standard laboratory HIT tests, and physicochemical methods to identify a plasma factor interfering with PF4/heparin complexes and anti-PF4/heparin antibody–platelet interaction, thus explaining differences in functional assays. To investigate a modulating risk for PF4/heparin immunization and breakthrough of HIT, we also tested 89 plasmas from 2 serosurveillance trials. Fibronectin levels were measured in 4 patient groups exhibiting different degrees of heparin-dependent immunization and expression of HIT. The heat-labile plasma protein, fibronectin, inhibited PF4 binding to platelets in a dose-dependent fashion, particularly in washed (vs PRP) systems. Fibronectin also inhibited PF4/heparin binding to platelets, anti-PF4/heparin antibody binding to PF4/heparin complexes, and anti-PF4/heparin antibody–induced platelet activation as a result of PF4/heparin complex disruption. In addition, plasma fibronectin levels increased progressively among the following 4 patient groups: enzyme-linked immunosorbent assay (ELISA)+/serotonin-release assay (SRA)+/HIT+ < ELISA+/SRA+/HIT− ∼ ELISA+/SRA−/HIT− < ELISA−/SRA−/HIT−. Altogether, these findings suggest that fibronectin interferes with PF4/heparin complex formation and anti-PF4/heparin antibody–induced platelet activation. Reduced fibronectin levels in washed platelet assays help to explain the greater sensitivity of washed platelet (vs PRP) assays for HIT. More importantly, lower plasma fibronectin levels could represent a risk factor for PF4/heparin immunization and clinical breakthrough of HIT.
Platelet-specific deletion of SNAP23 ablates granule secretion, substantially inhibiting arterial and venous thrombosis in mice
Authors: Williams Christopher M. , Li Yong , Brown Edward , Poole Alastair W.
Published: December 2018

Platelet secretion is central to physiological and pathophysiological platelet function. SNAP23 has long been implicated as being a principal SNARE protein regulating platelet granule secretion, although this has not been definitively demonstrated in genetic models. Here, using a platelet-specific conditional SNAP23 knockout mouse, we show that absence of SNAP23 results in complete ablation of dense granule, α granule, and lysosomal secretion. Measured granule cargo content and granule numbers were normal, suggesting SNAP23 regulates fusion of granules with the extracellular membrane, rather than granule loading or formation. A macrothrombocytopenia was also observed, which, combined with ablation of secretion, resulted in a pronounced bleeding defect in a tail bleed assay and almost complete ablation of arterial and venous thrombosis. The macrothrombocytopenia was not due to reduced megakaryopoiesis but instead likely was due to the increased loss of platelets through bleeding, consistent with an increase in platelet total RNA content indicating a greater number of reticulated platelets. The data definitively show SNAP23 to be critical for granule release of any kind from platelets, irrespective of stimulus, and this is the first single gene to be shown to be universally essential for exocytosis in platelets.
Association of outdoor temperature with lung function in a temperate climate
Authors: Rice Mary B. , Li Wenyuan , Wilker Elissa H. , Gold Diane R. , Schwartz Joel , Zanobetti Antonella , Koutrakis Petros , Kloog Itai , Washko George R. , O'Connor George T. , Mittleman Murray A.
Published: December 2018

Acute exposure to cold dry air is a trigger of bronchoconstriction, but little is known about how daily outdoor temperature influences lung function.

We investigated associations of temperature from a model using satellite remote sensing data with repeated measures of lung function among 5896 participants of the Framingham Heart Study Offspring and Third Generation cohorts residing in the Northeastern US. We further tested if temperature modified previously reported associations between pollution and lung function. We constructed linear mixed-effects models, and assessed departures from linearity using penalised splines.

In fully adjusted linear models, 1-, 2- and 7-day average temperatures were all associated with lower lung function: each 5°C higher previous-week temperature was associated with a 20 mL lower (95% CI −34­–−6) forced expiratory volume in 1 s. There was significant effect modification by season: negative associations of temperature and lung function were present in winter and spring only. Negative associations between previous-day fine particulate matter and lung function were present during unseasonably warm but not unseasonably cool days, with a similar pattern for other pollutants.

We speculate that temperature-related differences in lung function may be explained by behavioural changes on relatively warm days, which may increase outdoor exposures.
“T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin
Authors: Pavlidis Stelios , Takahashi Kentaro , Ng Kee Kwong Francois , Xie Jiaxing , Hoda Uruj , Sun Kai , Elyasigomari Vahid , Agapow Paul , Loza Matthew , Baribaud Fred , Chanez Pascal , Fowler Steve J. , Shaw Dominic E. , Fleming Louise J. , Howarth Peter H. , Sousa Ana R. , Corfield Julie , Auffray Charles , De Meulder Bertrand , Knowles Richard , Sterk Peter J. , Guo Yike , Adcock Ian M. , Djukanovic Ratko , Fan Chung Kian
Published: December 2018

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.

The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.

37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature.FeNO(≥30 ppb) and blood eosinophils (≥300 cells·µL−1) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.

T2-high severe asthma can be predicted to some extent from raised levels ofFeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.
Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study
Authors: Sun Feng , Li Yang , Chen Yu , Guan Wenlong , Jiang Xiangao , Wang Xiaomeng , Ren Pengfei , Li Junlian , Shi Jichan , He Guiqing , Wu Meiying , Tang Peijun , Wang Fei , Sheng Yunfeng , Huang Fuli , Zhou Zumo , Huang Heqing , Hong Liang , Liu Qihui , Zhang Ying , Zhang Wenhong
Published: December 2018

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18–24 months and has a poor cure rate of 50–60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.

We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.

Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3%versus55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1%versus62.1%, p=0.009).

Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.
COPD is associated with an increased risk of peripheral artery disease and mortality
Authors: Terzikhan Natalie , Lahousse Lies , Verhamme Katia M.C. , Franco Oscar H. , Ikram M. Arfan , Stricker Bruno H. , Brusselle Guy G.
Published: December 2018

Patients with chronic obstructive pulmonary disease (COPD) commonly present with multimorbidity. We aimed to investigate the association between COPD and the development of peripheral arterial disease (PAD) in the general population, and how this might affect mortality among individuals with COPD.

We included 3123 participants of the population-based Rotterdam Study without PAD at baseline (mean age 65 years; 57.4% female). The association between COPD at baseline and PAD during follow-up was studied using logistic regression (PAD being indicated by an ankle�brachial index (ABI) of 0.9 or less). Cox regression was used for mortality analysis and interaction terms were used to investigate mortality risk modification by PAD.

The presence of COPD was associated with incident PAD (adjusted odds ratio 1.9, 95% CI 1.1�3.2). Mortality rates per 100 000 person-years were as follows: 10.0 in individuals without COPD or PAD, 18.4 in those with COPD only, 16.1 in those with PAD only and 30.1 in individuals with both COPD and PAD. No statistical interaction was found between PAD and COPD on risk of dying.

Individuals with COPD have an almost doubled risk of developing PAD. Although PAD does not modify the association between COPD and mortality, people suffering from both diseases have substantially higher mortality rates.
Distributed acoustic sensing coupling noise removal based on sparse optimization
Authors: Chen Jianyou , Ning Junrui , Chen Wenchao , Wang Xiaokai , Wang Wei , Zhang Gulan
Published: December 2018

The industry treats the distributed acoustic sensing (DAS) system, which uses an optical fiber cable in vertical seismic profiling (VSP) data acquisition, as a new and fast-growing technology. The high-quality data set acquired from the DAS acquisition system can produce high-precision VSP images and obtain more detailed checkshots. However, in field data, the acquired VSP data set suffers from strong coherent DAS coupling noise. Many factors may cause coherent DAS coupling noise, such as the cable slapping and ringing due to the physical placement, the regular swing of the wireline in the well, and the uncoupling between the fiber cable and the casing. This DAS coupling noise reduces the signal-to-noise ratio and affects the subsequent processing and interpretation. Removing the DAS coupling noise can help to improve the quality of the VSP data set acquired with the DAS system. We have developed a sparse-optimization-based DAS coupling noise removing method. In the DAS-based VSP data set, the effective signal and the coupling noise have distinct morphological characteristics. The effective VSP signal has a wide bandwidth, whereas the DAS coupling noise appears in some narrow frequency bands in the frequency domain. The continuous wavelet transform and the discrete cosine transform can sparsely represent the effective VSP signal and DAS coupling noise, respectively. Therefore, we choose these two transforms as two sparse dictionaries and combine them to form an overcomplete dictionary. The morphological component analysis (MCA) can use the morphological difference between different components and the overcomplete dictionary to sparsely represent all components in the complicated signal. Based on the MCA theory, we use the block coordinate relaxation algorithm to separate the effective VSP signal and DAS coupling noise. Applications on a synthetic data set and two field data sets have validated the effectiveness of our method.
Effect of the SIRT1 gene on regional cortical grey matter density in the Han Chinese population
Authors: Rao Shuquan , Luo Na , Sui Jing , Xu Qi , Zhang Fuquan
Published: December 2018

Background

Our previous genome-wide association study (CONVERGE sample) identified significant association between single nucleotide polymorphisms (SNPs) near the SIRT1 gene and major depressive disorder (MDD) in Chinese populations.

Aims

To investigate whether SNPs across the SIRT1 gene locus affect regional grey matter density in the Han Chinese population.

Method

T1-weighted structural magnetic resonance imaging was conducted on 92 healthy participants from Eastern China. Grey matter was segmented from the image, which consisted of voxel-wise grey matter density. The effect of SIRT1 SNPs on grey matter density was determined by a multiple linear regression framework.

Results

SNP rs4746720 was significantly associated with grey matter density in two brain cortical regions: the orbital part of the right inferior frontal gyrus and the orbital part of the left inferior frontal gyrus (family-wise error-corrected P < 0.05; voxel-wise P < 0.001). Also, rs4746720 exceeded genome-wide significance in association with MDD in our CONVERGE sample (P = 3.32 × 10−08, odds ratio 1.161).

Conclusions

Our results provided evidence for a potential role of the SIRT1 gene in the brain, implying a possible pathophysiological mechanism underlying susceptibility to MDD.
Growth Hormone Deficiency: Health and Longevity
Authors: Aguiar-Oliveira Manuel H , Bartke Andrzej
Published: December 2018

The important role of GH in the control of mammalian longevity was first deduced from extended longevity of mice with genetic GH deficiency (GHD) or GH resistance. Mice with isolated GHD (IGHD) due to GHRH or GHRH receptor mutations, combined deficiency of GH, prolactin, and TSH, or global deletion of GH receptors live longer than do their normal siblings. They also exhibit multiple features of delayed and/or slower aging, accompanied by extension of healthspan. The unexpected, remarkable longevity benefit of severe endocrine defects in these animals presumably represents evolutionarily conserved trade-offs among aging, growth, maturation, fecundity, and the underlying anabolic processes. Importantly, the negative association of GH signaling with longevity extends to other mammalian species, apparently including humans. Data obtained in humans with IGHD type 1B, owing to a mutation of the GHRH receptor gene, in the Itabaianinha County, Brazil, provide a unique opportunity to study the impact of severe reduction in GH signaling on age-related characteristics, health, and functionality. Individuals with IGHD are characterized by proportional short stature, doll facies, high-pitched voices, and central obesity. They have delayed puberty but are fertile and generally healthy. Moreover, these IGHD individuals are partially protected from cancer and some of the common effects of aging and can attain extreme longevity, 103 years of age in one case. We think that low, but detectable, residual GH secretion combined with life-long reduction of circulating IGF-1 and with some tissue levels of IGF-1 and/or IGF-2 preserved may account for the normal longevity and apparent extension of healthspan in these individuals.
Sugammadex Reversal of a Large Subcutaneous Depot of Rocuronium in a Dialysis Patient: A Case Report
Authors: Navare Sagar R. , Garcia Medina Oscar , Prielipp Richard C. , Weinkauf Julia L.
Published: December 2018

Sugammadex is a modified gamma cyclodextrin that encapsulates rocuronium. We report the successful use of sugammadex in the management of an elderly man with end-stage renal failure who sustained an infiltration of subcutaneous rocuronium during rapid sequence induction of general anesthesia. Given the erratic absorption of subcutaneous rocuronium from the tissue, sugammadex was chosen to reverse the neuromuscular block at the end of the procedure. This report demonstrates the efficacy of sugammadex to reverse neuromuscular block in elderly patients with poor renal function. Moreover, the duration of action for sugammadex was sufficient to neutralize the ongoing absorption of subcutaneous rocuronium.
Mechanical forces in cell monolayers
Authors: Chen Tianchi , Saw Thuan Beng , Mège René-Marc , Ladoux Benoit
Published: December 2018

In various physiological processes, the cell collective is organized in a monolayer, such as seen in a simple epithelium. The advances in the understanding of mechanical behavior of the monolayer and its underlying cellular and molecular mechanisms will help to elucidate the properties of cell collectives. In this Review, we discuss recent in vitro studies on monolayer mechanics and their implications on collective dynamics, regulation of monolayer mechanics by physical confinement and geometrical cues and the effect of tissue mechanics on biological processes, such as cell division and extrusion. In particular, we focus on the active nematic property of cell monolayers and the emerging approach to view biological systems in the light of liquid crystal theory. We also highlight the mechanosensing and mechanotransduction mechanisms at the sub-cellular and molecular level that are mediated by the contractile actomyosin cytoskeleton and cell–cell adhesion proteins, such as E-cadherin and α-catenin. To conclude, we argue that, in order to have a holistic understanding of the cellular response to biophysical environments, interdisciplinary approaches and multiple techniques – from large-scale traction force measurements to molecular force protein sensors – must be employed.
Geriatric urinary tract infections: The value of laboratory parameters in estimating the need for bacteremia and Intensive Care Unit
Authors: Tartar Ayse Sagmak , Balin Safak Ozer
Published: December 2018

Objective: We investigated the geriatric patients diagnosed as urinary tract infection and evaluated the effects of white blood cell (WBC), neutrophil count, platelet, mean platelet volume (MPV), red cell distribution width (RDW), total bilirubin, direct bilirubin, creatine, albumin, erythrocyte sedimentation rate, C-reactive protein, and neutrophil/lymphocyte ratio parameters on estimating the need for bacteremia and intensive care (IC) for the patients with pyelonephritis

Methods: Between 2016-2017, a total number of 188 patients aged 65 years and above were retrospectively evaluated at the infectious diseases clinic.

Results: The 124 (66%) of the patients were male and 64 (34%) were female. The laboratory values of the patients with pyelonephritis and urosepsis were found to be significantly lower in only RDW bacteremic patients (p=0.047). The laboratory values during the application of third-step IC unit patients, who were treated and discharged, were compared. Albumin was significantly lower, while direct bilirubin, AST and ALT were significantly higher (p<0.05).

Conclusions: Patients, whose biochemical parameters have changed, especially during admission or follow-up, should be evaluated carefully in terms of urosepsis, multiple organ failure and IC need. A number of diagnostic tests have been described to predict the need for sepsis and IC. However, many of them cannot be performed in emergency conditions. It is a great advantage that the parameters we use in our work are easily accessible and can be performed in emergency conditions.

How to cite this:Tartar AS, Balin SO. Geriatric urinary tract infections: The value of laboratory parameters in estimating the need for bacteremia and Intensive Care Unit. Pak J Med Sci. 2019;35(1):215-219. doi: https://doi.org/10.12669/pjms.35.1.97

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque?
Authors: Schwartz Stephen M. , Virmani Renu , Majesky Mark W.
Published: December 2018

Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture.

Four advances have made it important to reconsider Benditt’s observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the “soil” for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called “smooth muscle cells”, we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal.

As a result, Benditt’s hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis?
Making gene editing a therapeutic reality
Authors: Conboy Irina , Murthy Niren , Etienne Jessy , Robinson Zachery
Published: December 2018

This review discusses current bottlenecks in making CRISPR-Cas9-mediated genome editing a therapeutic reality and it outlines recent strategies that aim to overcome these hurdles as well as the scope of current clinical trials that pioneer the medical translation of CRISPR-Cas9. Additionally, this review outlines the specifics of disease-modifying gene editing in recessive versus dominant genetic diseases with the focus on genetic myopathies that are exemplified by Duchenne muscular dystrophy and myotonic dystrophies.
Mean deviation based identification of activated voxels from time-series fMRI data of schizophrenia patients
Authors: Chatterjee Indranath
Published: December 2018

Background: Schizophrenia is a serious mental illness affecting different regions of the brain, which causes symptoms such as hallucinations and delusions. Functional magnetic resonance imaging (fMRI) is the most popular technique to study the functional activation patterns of the brain. The fMRI data is four-dimensional, composed of 3D brain images over time. Each voxel of the 3D brain volume is associated with a time series of signal intensity values. This study aimed to identify the distinct voxels from time-series fMRI data that show high functional activation during a task.

Methods: In this study, a novel mean-deviation based approach was applied to time-series fMRI data of 34 schizophrenia patients and 34 healthy subjects. The statistical measures such as mean and median were used to find the functional changes in each voxel over time. The voxels that show significant changes for each subject were selected and thus used as the feature set during the classification of schizophrenia patients and healthy controls.

Results: The proposed approach identifies a set of relevant voxels that are used to distinguish between healthy and schizophrenia subjects with high classification accuracy. The study shows functional changes in brain regions such as superior frontal gyrus, cuneus, medial frontal gyrus, middle occipital gyrus, and superior temporal gyrus.

Conclusions: This work describes a simple yet novel feature selection algorithm for time-series fMRI data to identify the activated brain voxels that are generally affected in schizophrenia. The brain regions identified in this study may further help clinicians to understand the illness for better medical intervention. It may be possible to explore the approach to fMRI data of other psychological disorders.
Formation by Younger Schoolchildren of the Ability to Learn in the Process of Performing Olympiad Mathematical Tasks
Authors: Чиркова Н. , Chirkova N. , Павлова О. , Pavlova O.
Published: December 2018

The pedagogical problem of the formation of the ability to learn as a set of universal skills in conjunction with objective actions is considered in the article based on the performance of olympiad mathematical tasks by younger schoolchildren. The requirements for the development and formulation of olympiad tasks, with the help of which a set of pedagogical activities are implemented, contributing to the development of the ability to learn by children of primary school age. The types of Olympiad tasks offered by the authors are connected with the main thematic sections of the initial course of mathematics.
Information and Communication Technologies As Means of Creative Development of Primary Schoolchildren
Authors: Мерзликина И. , Merzlikina I.
Published: December 2018

The article reveals the possibilities of using information and communication technologies in order to develop the creative abilities of younger schoolchildren. Using the example of preparing an independent thematic message, it demonstrates how the interaction of the learner with the means of information and communication technologies should be organized in order to achieve the developmental effect of learning.
Theoretical Approach to the Development of a Program of Economic Culture Formation by Orphaned Children of Primary School Age
Authors: Шахманова А. , Shakhmanova A. , Саидова М. , Saidova M.
Published: December 2018

The article reveals the main directions of the content of the economic component of the education and upbringing of younger schoolchildren. It emphasizes the relevance of this problem for orphans raised in an orphanage, since the development of their economic literacy eliminates potential difficulties and ensures more successful process of further socialization of the growing personality. Particular attention is paid in the

article to the theoretical foundations of the development of a program for the formation of an economic culture among pupils of primary school age.
Integration of the Content of Educational Subjects of the Aesthetic Cycle in the Classes in the Elementary Grade
Authors: Петрашко Ольга , Petrashko O.
Published: December 2018

The article gives advice to the teacher on the use of creative tasks in the process of working with younger schoolchildren in the classroom of visual arts, literary reading, music and the outside world. It is shown how when planning lessons one can take into account the specifics of the content of a school subject for constructing creative tasks based on the integration of the content of the topics studied.
The Principle of Least Action in Logistics
Authors: Бабанов В. , Babanov V. , Хомяков В. , Homyakov V.
Published: December 2018

The article deals with the application of the Principle of least action in logistics, as well as some issues of building a rational logistics based on this principle; logistics is the management of the movement of material and related information and financial flows on the way from the primary source of resources to the final consumer of finished products with minimal costs; logistics is a key link between the supplier and the buyer, capable of competently constructed work to increase the utility of products and profits of the enterprise; one of the tasks of logistics is to reduce the specific energy costs of workers involved in ensuring the movement of material flows; according to the principle of least action, logistics activities should be organized so that the total cost of resources is minimal.
The Formation of a System of Views on the Process of Management of Sustainable Development of the Region
Authors: Жуков Р. , Zhukov R. , Поляков В. , Polyakov V. , Васина М. , Vasina M. , Соболева Д. , Soboleva D.
Published: December 2018

The approaches to the process of management of complex systems, including from the standpoint of technical and socio-economic and ecological views are analyzed. Their proximity, both in methodological and instrumental terms, is shown. The system of views on the process of management of sustainable development of the region is formed, considered as a socio-ecological and economic system. Terms, principles and tools are generalized and formulated for the management process, including the justification for the use of economic and mathematical apparatus and information technology tools for its optimization.
Game-Theoretic Modeling in Practice of Decision-Making
Authors: Власов Дмитрий , Vlasov Dmitriy
Published: December 2018

In recent years application of game-theoretic modeling for decisionmaking in various fields of economic activity became very popular. However not enough researches are conducted for the purpose of determination of adequacy and efficiency of such use, questions of orientation of various game models on the solution of specific objectives of the theory of decision-making are not fully described. The relevance of a subject of article is caused by increase of interests in game theory and game modeling as to the tool of the solution of various problems of decision-making in the conditions of risk and uncertainty. The allocated contexts of application of game theory in practice of decisionmaking formed the basis of the electronic educational resource «Game theory» which became an integral part of vocational training of bachelors in Plekhanov Russian University of Economics. The presented results can be used for improvement of quality of the made decisions.
On the Problems of Short Term Forecasting of Russian Stock Market
Authors: Галустян М. , Galustyan M.
Published: December 2018

The features of the Russian stock market that affect the process and the result of forecasting its main indicator — MICEX — are considered, the mechanism that makes it difficult to predict the index for each of the features is described. A comparative analysis of the Russian stock market with the stock markets of other countries in accordance with the above features. Using the mathematical and statistical methods the increased influence of these features and problems on the Russian stock market in comparison with the stock markets of other BRIC countries, developed countries, the Eurozone countries is proved. The paper uses such methods as: correlation analysis, graphical analysis, analysis of variance, comparison method, method of retrospection. Monthly and daily data for 2010–2017 are used in calculations and graphs.
Spatial and temporal variations of K Ca II line profile shapes in different structures of the solar chromosphere. I. Features of individual profiles
Authors: Турова Ирина , Turova Irina , Григорьева София , Grigoryeva Sofiya , Ожогина Ольга , Ozhogina Olga
Published: December 2018

We have studied Ca II K line profiles, using two time series of spectrograms taken in two regions near the solar disk center. In each of the regions, the spectrograph slit cut out several areas of the quiet region and a plage. For the selected chromospheric structures, we have derived K line profiles and have defined a number of parameters that characterize the spatial and temporal variations of the profiles. The analysis of profile shapes in different structures belonging to the same moment of time has shown that there are structures whose profiles differ only slightly from each other in the photosphere, but differ dramatically in the chromosphere. The structures begin to differ from the level of formation of K1 and continue to differ further in the chromosphere. There are, however, structures which begin to differ at the level of the photosphere and continue to differ in the chromosphere. The difference between profile shapes in different structures is likely to be associated both with different thermodynamic conditions and with different magnetic field topology at a given point at a given time. We have examined temporal variations of the K Ca II line profiles in structural chromospheric elements, which are caused by the process of K2v-grains. In most of the studied areas of the chromospheric structures, the brightening of the K2v peak develops according to the “common” scenario: at the time of maximum bright-ness, the line shifts toward the red side. There are, however, cases when the brightening of the K2v peak occurs with a shift of the line to the violet side or with no shift at all. We have constructed scatter plots for some pairs of profile parameters related to intensities at characteristic points of the profile and their shifts. A correlation has been found between intensities in the center and wings of the K line. The correlation between shifts of the K2v and K2r peaks is very weak or completely absent.
Financial accounting
Authors: Никандрова Лариса , Nikandrova Larisa , Акатьева Марина , Akateva Marina
Published: December 2018

A systematic, comprehensive and professional presentation on accounting of the organization's capital, its main assets, intangible assets and inventories; - accounting of labour and its payment; accounting of cash and accounting operations; accounting of production costs and selling products, financial investments and results on the basis of existing normative and legislative documents, regulations on accounting.
For students in the field of training 38.03.01 "Economics" of all profiles, specialists of economic and financial services of organizations, auditors.
Battle of the Internet Channels: How Do Mobile and Fixed-Line Quality Drive Internet Use?
Authors: Xu Jiao , Forman Chris , Hu Yu Jeffrey
Published: December 2018

We study whether and under what conditions mobile Internet networks compete with traditional fixed-line Internet networks by examining how the quality of local fixed-line Internet service influences mobile Internet adoption and use. Empirical analysis shows that a 1 megabits per second (Mbps) increase in local fixed-line Internet speed leads to a 14.9% decline in the likelihood of purchasing a mobile data plan. However, we show there are substantial differences in the extent to which users view these channels as competitors based on individual- and location-specific characteristics and the nature of the application. Fixed-line Internet speed has no effect on the use of mobile offline services, such as taking photos or videos, that do not require a real-time Internet connection. Younger users and those who live in areas with lower fixed-line Internet speeds find the channels to be closer competitors.

The online appendix is available at https://doi.org/10.1287/isre.2018.0776 .
Research roundup
Authors: Heggs Karen
Published: December 2018

Synopses of a selection of recently published research articles of relevance to palliative care
Placebo: A clinical, biological and ethical enigma
Authors: Greener Mark
Published: December 2018

Mark Greener explains the history of using placebos in medicine
The development of cadaveric simulation for core surgical trainees
Authors: Hughes JL , Katsogridakis E , Junaid-Siddiqi A , Pollard JS , Bedford JD , Coe PO , Jones DJ
Published: December 2018

How valuable is cadaveric simulation as an educational tool?
Low impact
Authors: Harley SJD , Eldredge TA , Warren LR , Shenfine J
Published: December 2018

Junior surgeons’ perceptions of their own research
The key to better outcomes
Authors: Alderson Derek
Published: December 2018

Our president draws attention to the importance of collaboration within and between institutions to improve patient care.
The face of Hong Kong
Authors: Yiu Yan Leung Mike , Shan Choi Wing , Thomson Peter
Published: December 2018

We have reported previously on the organisation of oral and maxillofacial surgery (OMFS) services in Hong Kong, and the role of the academic discipline within the Faculty of Dentistry at the University of Hong Kong. 1 This article reviews OMFS involvement in the management of dental and facial deformity, with particular reference to the treatment needs of the local population.
Rosana’s house
Authors: Michelotti Graciela
Published: December 2018

This article compares Roquet’s short with García Lorca’s La casa de Bernarda Alba (1936), exploring how relationships between maids and female employers have been preserved despite the passage of time. When framed by the incidence of class differences, long-held traditions and repressed emotions, silence dominates both texts.
Haunting analysis: The audio-visual essay
Authors: Outzen Mads
Published: December 2018

This article reflects upon the audio-visual essay as academic work and work of art, exploring Martin and Álvarez López’ short to demonstrate that this form of cinematic experimentation is indeed both things – providing analytical examination of the cinema of Víctor Erice as well as creating a new poetic experience in itself.
Critical haunting
Authors: Law Hoi Lun
Published: December 2018

A distinctive feature of Haunted Memory is its evocative interplay between voice-over and visual that suspends the viewer – not unlike the curious-child in Víctor Erice’s films – in a position between understanding and non-understanding. This article explores how the practice of the audio-visual essay presents an opportunity to exploit critical uncertainty.
O Europeu e os seus penates
Authors: Cordeiro Cristina Robalo
Published: December 2018

Onde se sente o Europeu verdadeiramente em casa senão na sua formação intelectual,na sua língua materna e na sua confissão religiosa? É à luz desta tripla determinaçãoque examinamos a imagem da “casa europeia”, ao mesmo tempo, como qualquer casa,inclusiva e exclusiva. Mas a esse sentimento de familiaridade e de pertença opõe-se cadavez mais a angústia de uma despossessão. As normas da cultura universitária e as condiçõesda sua permanência estão ameaçadas, a liberdade de falar a sua língua nacional,em vez de uma “lingua franca” limitativa, vê-se reduzida ao espaço privado, o direitode atestar a inspiração cristã da Europa histórica e comunitária exerce-se com crescentereticência. Como não experimentaria o Europeu, identificando-se com estes valores contestados,os seus “penates”, o doloroso sentimento de ver a sua casa irremediavelmentehipotecada?
Hombres cuidadores informales en la ciudad de Valencia. Una experiencia de reciprocidad
Authors: Rodríguez del Pino Juan Antonio , Samper Gras Teresa , Marín Traura Susana , Sigalat Signes Enric , Moreno Ruiz Elisa
Published: December 2018

Este artículo forma parte de un estudio de la Universidad de Valencia donde se analiza la percepción que algunos hombres tienen acerca del cuidado de personas adultas (mayores y/o discapacitadas) que ellos realizan de manera informal en su entorno familiar en la ciudad de Valencia. A través de entrevistas en profundidad, identificamos, la responsabilidad que estos hombres se toman con la persona cuidada a través del establecimiento de procesos de reciprocidad. Dicha reciprocidad destaca como un elemento positivo a extraer de sus vivencias que permite reivindicar el cuidado como un valor positivo y no exclusivo de ningún género.