bluuebunny/crossref_metadata_2025 huggingface dataset:
Extraciliary roles of the ciliopathy protein JBTS17 in mitosis and neurogenesis
Authors: Hong Hyowon , Joo Kwangsic , Park Sang Min , Seo Jimyung , Kim Min Hwan , Shin EunBie , Cheong Hae Il , Lee Jeong Ho , Kim Joon
Published: April 2019

Objective

JBTS17 is a major gene mutated in ciliopathies such as Joubert syndrome and oral–facial–digital syndrome type VI. Most patients with loss of function mutations in JBTS17 exhibit cerebellar vermis hypoplasia and brainstem malformation. However, some patients with JBTS17 mutations show microcephaly and abnormal gyration. We examined potential roles of JBTS17 in neurogenesis to understand the pathological mechanism of JBTS17‐related cortical abnormalities.

Methods

We examined subcellular localization and cell‐cycle–dependent expression of JBTS17 proteins using anti‐JBTS17 antibodies and JBTS17 expression vectors. We also performed knockdown experiments to determined roles of JBTS17 in human cells, and demonstrated mitotic functions of JBTS17 using immunostaining and live imaging. We examined the involvement of JBTS17 in cortical neurogenesis using a mouse in utero electroporation technique.

Results

We found that JBTS17 localizes to the kinetochore and the level of JBTS17 is regulated by cell‐cycle–dependent proteolysis. Depletion of JBTS17 disrupts chromosome alignment and spindle pole orientation, resulting in mitotic delay. JBTS17 interacts with LIS1 and influences LIS1 localization. Depletion of Jbts17 in the developing mouse cortex interferes with the mitotic progression of neural progenitors and the migration of postmitotic neurons.

Interpretation

LIS1 is implicated in lissencephaly, but altered dosage of LIS1 has been also associated with microcephaly syndromes. Our results suggest that JBTS17 contributes to mitotic progression by interacting with LIS1, and abnormal mitosis is an underlying mechanism of the microcephaly phenotype in JBTS17‐related ciliopathies. We propose that understanding extraciliary roles of ciliopathy proteins is important to elucidate pathological mechanisms underlying diverse ciliopathy phenotypes. ANN NEUROL 2019
Rotaxane Probes for the Detection of Hydrogen Peroxide by 129Xe HyperCEST NMR Spectroscopy
Authors: Klass Sarah H. , Truxal Ashley E. , Fiala Tahoe A. , Kelly Joseph , Nguyen Dang , Finbloom Joel A. , Wemmer David E. , Pines Alexander , Francis Matthew B.
Published: April 2019

The development of sensitive and chemically selective MRI contrast agents is imperative for the early detection and diagnosis of many diseases. Conventional responsive contrast agents used in 1H MRI are impaired by the high abundance of protons in the body. 129Xe hyperCEST NMR/MRI comprises a highly sensitive complement to traditional 1H MRI because of its ability to report specific chemical environments. To date, the scope of responsive 129Xe NMR contrast agents lacks breadth in the specific detection of small molecules, which are often important markers of disease. Herein, we report the synthesis and characterization of a rotaxane‐based 129Xe hyperCEST NMR contrast agent that can be turned on in response to H2O2, which is upregulated in several disease states. Added H2O2 was detected by 129Xe hyperCEST NMR spectroscopy in the low micromolar range, as well as H2O2 produced by HEK 293T cells activated with tumor necrosis factor.
A Key Intermediate in Copper‐Mediated Arene Trifluoromethylation, [nBu4N][Cu(Ar)(CF3)3]: Synthesis, Characterization, and C(sp2)−CF3 Reductive Elimination
Authors: Lu Zehai , Liu He , Liu Shihan , Leng Xuebing , Lan Yu , Shen Qilong
Published: April 2019

The synthesis, characterization, and C(sp2)−CF3 reductive elimination of stable aryl[tris(trifluoromethyl)]cuprate(III) complexes [nBu4N][Cu(Ar)(CF3)3] are described. Mechanistic investigations, including kinetic studies, studies of the effect of temperature, solvent, and the para substituent of the aryl group, as well as DFT calculations, suggest that the C(sp2)−CF3 reductive elimination proceeds through a concerted carbon–carbon bond‐forming pathway.
Molecular characterization and expression analysis of a phosphoserine aminotransferase involving l‐serine synthesis from silkworm, Bombyx mori
Authors: Haque Mohammad R. , Hirowatari Aiko , Koyanagi Ayumi , Ichinose Takashi , Abiru Maiko , Mohri Shinya , Furuya Shigeki , Yamamoto Kohji
Published: April 2019

In this study, we identified and characterized a phosphoserine aminotransferase (bmPSAT) from Bombyx mori (B. mori) that is responsible for l‐serine biosynthesis. A complementary DNA that encodes bmPSAT was cloned by reverse transcriptase polymerase reaction and sequenced. The presumed amino acid sequence revealed 47–87% identity with known PSATs from insects, humans, plants, and bacteria. Through phylogenetic analysis, we found that bmPSAT is evolutionary related to insect PSATs. Recombinant bmPSAT was produced in Escherichia coli by using a cold‐shock promotor and purified to homogeneity. This enzyme utilizes phosphohydroxypyruvate and glutamate for transamination. bmPSAT messenger RNA (mRNA) was expressed at higher levels in several tissues of standard strain silkworm including the silk gland, whereas a sericin‐deficient silkworm strain exhibited a diminished expression of bmPSAT mRNA in the silk gland. These findings indicate that bmPSAT may play an important role in synthesizing and supplying l‐serine in the larva of B. mori.
Neural substrates of self‐ and external‐preoccupation: A voxel‐based morphometry study
Authors: Ikeda Shigeyuki , Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Yokoyama Ryoichi , Nakagawa Seishu , Sekiguchi Atsushi , Iizuka Kunio , Hanawa Sugiko , Araki Tsuyoshi , Miyauchi Carlos Makoto , Sakaki Kohei , Nozawa Takayuki , Yokota Susumu , Magistro Daniele , Kawashima Ryuta
Published: April 2019

Introduction

Self‐ and external‐preoccupation have been linked to psychopathological states. The neural substrates underlying self‐ and external‐preoccupation remain unclear. In the present study, we aim to provide insight into the information‐processing mechanisms associated with self‐ and external‐preoccupation at the structural level.

Methods

To investigate the neural substrates of self‐ and external‐preoccupation, we acquired high‐resolution T1‐weighted structural images and Preoccupation Scale scores from 1,122 young subjects. Associations between regional gray matter volume (rGMV) and Preoccupation Scale subscores for self‐ and external‐preoccupation were estimated using voxel‐based morphometry.

Results

Significant positive associations between self‐preoccupation and rGMV were observed in widespread brain areas such as the bilateral precuneus and posterior cingulate gyri, structures known to be associated with self‐triggered self‐reference during rest. Significant negative associations between external‐preoccupation and rGMV were observed only in the bilateral cerebellum, regions known to be associated with behavioral addiction, sustained attention, and reward system.

Conclusion

Our results reveal distinct neural substrates for self‐ and external‐preoccupation at the structural level.
Fascial entrapment neuropathy
Authors: Stecco Antonio , Pirri Carmelo , Stecco Carla
Published: April 2019

Entrapment neuropathies are debilitating clinical conditions, creating significant morbidity in the upper and lower extremities in terms of pain, sensory abnormalities, and motor weakness, becoming a challenge to diagnose and treat. Because entrapments can have multiple origins, a misinterpretation of anatomy during examination can lead to incorrect diagnosis and treatment. This review addresses understanding of the anatomy of fascia that can play an important role in this syndrome. There is a specific microenvironment around the nerve composed of connective tissues that include deep fascia, intermuscular septa, epineurium, and perineurium. The microenvironmental modifications can be translated into change in mobility with consequence decreasing of the independency of the nerve from the surrounding structures lading to entrapments and “internal stretch lesion.” The entrapments reported in this article reinforce the importance of fascia tissue in generating common symptoms that pose more difficult diagnostic challenges and may often be confused with more common clinical conditions. Clin. Anat. 32:883–890, 2019. © 2019 Wiley Periodicals, Inc.
Fulvestrant in the treatment of hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer: A review
Authors: Li Junjie , Wang Zhonghua , Shao Zhimin
Published: April 2019

Nearly 75% of breast cancers are hormone receptor‐positive (HR+) and human epidermal growth factor receptor type 2‐negative (HER2−), making endocrine therapy the mainstay of treatment for HR+ and HER2− combination. Although endocrine therapy, such as therapy with fulvestrant, is widely used in the clinic, endocrine resistance (primary or secondary) is inevitable and poses a serious clinical concern. However, the therapeutic landscape of HR+/HER2− breast cancer is rapidly changing and evolving. In recent years, molecular insights into the genome of HR+/HER2− breast cancer have helped to identify promising targets, such as alterations in signaling pathways [phosphatidylinositide 3‐kinase (PI3K/AKT/mammalian target of rapamycin (mTOR)], dysregulation of the cell cycle (CDK4/6), and identification of new ESR1 mutations. These insights have led to the development of newer targeted therapies, which aims at significantly improving survival in these patients. This review summarizes the role and rationale of fulvestrant when used as a monotherapy or in combination with targeted therapies in patients with HR+/HER2− advanced breast cancer. We also discuss other novel agents and potential future combination treatment options.
Fe/Fe3C Nanoparticles Encapsulated in N‐Doped Hollow Carbon Spheres as Efficient Electrocatalysts for the Oxygen Reduction Reaction over a Wide pH Range
Authors: Liu Yanhui , Wang Xingkun , Zhao Bolin , Shao Xin , Huang Minghua
Published: April 2019

Nonprecious‐metal‐based electrocatalysts with low cost, high activity, and stability are considered as one of the most promising alternatives to Pt‐based catalysts for the oxygen reduction reaction (ORR). Herein, an economical and easy‐to‐fabricate catalyst is developed, that is, Fe/Fe3C embedded in N‐doped hollow carbon spheres (Fe/Fe3C/NHCS), which gave the half‐wave potential of 0.84 V in 0.1 m KOH, similar to the commercial Pt/C catalyst. Surprisingly, the favorable ORR performance of the as‐prepared catalyst was obtained in both acidic and neutral conditions with almost a four‐electron pathway and low H2O2 yield, which desirable the development of the proton exchange membrane (PEM) and microbial electrolysis cell (MEC) technology. Additionally, the obtained catalyst demonstrated better long‐term stability and high methanol tolerance over a wide range of pH. These features could be mainly attributed to the synergistic effect between Fe/Fe3C and Fe‐Nx sites, the hollow structure with mesopores, and the well‐dispersed Fe/Fe3C nanoparticles owing to the existence of the abundant hydrophilic groups within the HCS precursor. As such, designing an efficient and cheap ORR catalyst that can operate at alkaline, acidic, and neutral solutions is highly desirable, yet challenging.
Come Dance With Me: Transformative Changes in the Science and Practice of Drug–Drug Interactions
Authors: Venkatakrishnan Karthik , Rostami‐Hodjegan Amin
Published: April 2019

The past 2 decades have witnessed transformative changes in our approach to drug–drug interactions (DDIs) from scientific research to clinical practice. Collaborative cooperation across the sectors of academia, pharmaceutical industry, providers of translational research tools and services, global regulatory agencies, and healthcare providers has created and galvanized a science‐informed and patient‐centered approach. Multidisciplinary innovations in mechanistic assessment of absorption, distribution, metabolism, and excretion (ADME), population pharmacology and pharmacogenetics, physiologically based modeling, and regulatory science have enabled a profound shift in mindset from risk aversion to informative prescribing guidance for optimal risk management. Foundational to this transformation is a commitment to maximizing the value of innovative therapeutics for all patients and across clinical contexts of use through rational knowledge management and translation based on the totality of best available evidence, thereby removing the void that can lead to arbitrary decisions in clinical therapeutics.
A Realistic Review of the Drug‐Injury Relief System in Taiwan: Challenges, Lessons, and Achievements
Authors: Chen Wen‐Wen , Chien Mei‐Yi , Wu Wan‐Lun , Chiou Mu‐Han
Published: April 2019

The drug‐injury relief system in Taiwan was implemented 20 years ago with the goal of providing timely relief for drug injuries incurred by the proper use of legal drugs. This system utilizes a nonlitigation expert review process to evaluate drug‐injury relief applications, and 2,732 applications have been reviewed from 1999−2016. Of these, 1,572 applications received relief payments, an approval rate of 58%. Average review timeframes per application have decreased from 248 days (2003–2011) to 182 days (2012–2016). Most adverse drug reactions (ADRs) for approved cases involved skin and subcutaneous tissue disorders (67%), with allopurinol being the primary culprit drug. A recent decline observed for such ADRs may reflect the influences of promotional activities and policy initiatives carried out according to informed analysis from drug‐injury relief applications, which suggests that the drug‐injury relief system can also play an important public health role in enhancing drug safety.
The impact of maternal stress on infant alpha‐amylase is buffered by high infant regulation and low infant negative reactivity
Authors: Liu Jingwen , Kamin Hayley S. , Kurtevski Sara , Kelly Maria , Kertes Darlene A.
Published: April 2019

This study examined the main and interactive effects of maternal perceived stress and infant temperament—surgency, negative affectivity, and orienting/regulation—on infant salivary alpha‐amylase (sAA) responses to stress. Saliva samples were collected prior to and following two naturalistic stressors: maternal separation conducted at 9 months and blood draw/immunizations conducted at 12 months. sAA area under the curve (AUC) was computed to determine response of the sympathetic nervous system to each stressor. Results revealed significant interactions of maternal stress and infant negative affectivity and orienting/regulation with sAA AUC. Relations between maternal stress and infant sAA AUC were stronger among infants with higher levels of negative affectivity and lower levels of orienting/regulation. These results highlight the need to examine both infant characteristics and environmental factors when investigating the development of stress response systems.
Alterations in Cortical Morphology after Neonatal Stroke: Compensation in the Contralesional Hemisphere?
Authors: Al Harrach Mariam , Rousseau François , Groeschel Samuel , Wang Xiaoyu , Hertz‐pannier Lucie , Chabrier Stéphane , Bohi Amine , Lefevre Julien , Dinomais Mickael ,   on behalf of the AVCnn group
Published: April 2019

Although neonatal arterial ischemic stroke is now well‐studied, its complex consequences on long‐term cortical brain development has not yet been solved. In order to understand the brain development after focal early brain lesion, brain morphometry needs to be evaluated using structural parameters. In this work, our aim was to study and analyze the changes in morphometry of ipsi‐ and contralesional hemispheres in seven‐year‐old children following neonatal stroke. Therefore, we used surface‐based morphometry in order to examine the cortical thickness, surface area, cortical volume, and local gyrification index in two groups of children that suffered from neonatal stroke in the left (n = 19) and right hemispheres (n = 15) and a group of healthy controls (n = 30). Reduced cortical thickness, surface area, and cortical volumes were observed in the ipsilesional hemispheres for both groups in comparison with controls. For the group with left‐sided lesions, higher gyrification of the contralesional hemisphere was observed primarily in the occipital region along with higher surface area and cortical volume. As for the group with right‐sided lesions, higher gyrification was detected in two separate clusters also in the occipital lobe of the contralesional hemisphere, without a significant change in cortical thickness, surface area, or cortical volume. This is the first time that alterations of structural parameters are detected in the “healthy” hemisphere after unilateral neonatal stroke indicative of a compensatory phenomenon. Moreover, findings presented in this work suggest that lesion lateralization might have an influence on brain development and maturation.
Transcriptomic analysis of differential gene expression during chick periocular neural crest differentiation into corneal cells
Authors: Bi Lian , Lwigale Peter
Published: April 2019

Background

Multipotent neural crest cells (NCC) contribute to the corneal endothelium and keratocytes during ocular development, but the molecular mechanisms that underlie this process remain poorly understood. We performed RNA‐Seq analysis on periocular neural crest (pNC), corneal endothelium, and keratocytes and validated expression of candidate genes by in situ hybridization.

Results

RNA‐Seq profiling revealed enrichment of genes between pNC and neural crest‐derived corneal cells, which correspond to pathways involved in focal adhesion, ECM‐receptor interaction, cell adhesion, melanogenesis, and MAPK signaling. Comparisons of candidate NCC genes to ocular gene expression revealed that majority of the NCC genes are expressed in the pNC, but they are either differentially expressed or maintained during corneal development. Several genes involved in retinoic acid, transforming growth factor‐β, and Wnt signaling pathways and their modulators are also differentially expressed. We identified differentially expressed transcription factors as potential downstream candidates that may instruct expression of genes involved in establishing corneal endothelium and keratocyte identities.

Conclusion

Combined, our data reveal novel changes in gene expression profiles as pNC differentiate into highly specialized corneal endothelial cells and keratocytes. These data serve as platform for further analyses of the molecular networks involved in NCC differentiation into corneal cells and provide insights into genes involved in corneal dysgenesis and adult diseases.
Temporal and abiotic fluctuations may be preventing successful rehabilitation of soil‐stabilizing biocrust communities
Authors: Young Kristina E. , Bowker Matthew A. , Reed Sasha C. , Duniway Michael C. , Belnap Jayne
Published: April 2019

Land degradation is a persistent ecological problem in many arid and semiarid systems globally (drylands hereafter). Most instances of dryland degradation include some form of soil disturbance and/or soil erosion, which can hinder vegetation establishment and reduce ecosystem productivity. To combat soil erosion, researchers have identified a need for rehabilitation of biological soil crusts (biocrusts), a globally relevant community of organisms aggregating the soil surface and building soil fertility. Here, the impact of plant and biocrust cover was tested on soil erosion potential in the piñon–juniper woodlands of Bandelier National Monument,New Mexico, USA. Biocrusts were found to be similarly influential to vascular plants in reducing erosion, largely acting by promoting surface roughness. The potential to rehabilitate biocrusts within the Monument was also tested. Plots were inoculated on eroding soils before the summer monsoon with greenhouse‐cultured biocrusts. In a full‐factorial design, treatments to reduce or halt erosion were administered to the inoculated plots and their paired controls. These erosion‐reduction treatments included barriers to overland flow (flashing), slash placement, and seeding of vascular plants. Dynamic changes to soil stability, penetration resistance, and extractable soil nutrients were observed through time, but no strong effects with the addition of biocrust inoculum, seeding, or erosion intervention treatments were seen. The results do suggest possible ways forward to successfully rehabilitate biocrust, including varying the timing of biocrust application, amending inoculum application with different types of soil stabilization techniques, and adding nutrients to soils. The insights gleaned from the lack of response brings us closer to developing effective techniques to arrest soil loss in these socially and ecologically important dryland systems.
A Versatile Polymeric Precursor to High‐Performance Silicon Composite Anode for Lithium‐Ion Batteries
Authors: Yang Kai , Yu Zhihao , Yu Changcheng , Zhu Min , Yang Luyi , Chen Haibiao , Pan Feng
Published: April 2019

Silicon is a promising anode material for lithium‐ion batteries due to its very high theoretical capacity. Herein, a Si/SiOx@C composite anode is prepared from a polymeric precursor, and the performance of the anode is optimized by controlling the composition of the polymeric precursor. The precursor is produced by cross‐linking divinyl benzene (DVB) and polymethylhydrosiloxane (PMHS). Silicon nanoparticles are formed from the precursor via a molten‐salt reduction process, and a conductive SiOx@C matrix is produced through a subsequent pyrolysis process. As the ratio between DVB and PMHS is adjusted to 2:1, the specific capacity and rate performances of the resulting Si/SiOx@C composite reach the optima. Both the composition and the microstructure of the composite are affected by the composition of the precursor, and, in turn, they determine the performance of the composite anode.
The pre‐79 CE alluvial environment south of Pompeii's city walls
Authors: Nicosia Cristiano , Bonetto Jacopo , Furlan Guido , Musazzi Simona
Published: April 2019

The environment in the suburban area of Pompeii between Porta Marina and Porta Stabia at the time of the 79 CE volcanic event was investigated by means of a series of core drillings. These revealed the presence of a ubiquitous dark brown layer (referred to as “Phase 2 interval”) immediately below the 79 CE eruption deposits. Its stratigraphic interpretation relied on 14C dates, diatom analysis and micromorphology, and on comparisons and correlations with the available stratigraphic logs and excavation data. Phase 2 interval represents the sedimentary accretion that took place from ca. 900–750 cal a BCE to 79 CE. Its formation is the result of periodic flooding by the Sarno river in this distal reach of its floodplain (i.e., backswamps). The resulting picture is that of a patchy environment with weakly developed alluvial soil juxtaposed to areas with stagnating waters. No indication of artificial or natural watercourses derived from the Sarno river, of navigable lagoons, or of harbor basins was found.
Impact of sampling rate on statistical significance for single subject fMRI connectivity analysis
Authors: James Oliver , Park Hyunjin , Kim Seong‐Gi
Published: April 2019

A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity.
Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress
Authors: Li Qing , Pan Xiongxiong , Zhu Deming , Deng Zhengming , Jiang Runqiu , Wang Xuehao
Published: April 2019

Glucose metabolism reprogramming, which is a well‐established characteristic of multiple cancers, demands a higher rate of glycolysis to meet the increasing demands for macromolecular synthesis and to maintain rapid proliferation in a hypoxic environment. However, the mechanism underlying this switch remains to be elucidated. In this study, we investigated the function of circular RNA MAT2B (circMAT2B) in hepatocellular carcinoma (HCC) glucose metabolism reprogramming and malignancy. CircMAT2B was identified by bioinformatics analysis of Gene Expression Omnibus data sets. CircMAT2B expression was up‐regulated in HCC tissues and cell lines. HCC patients with high circMAT2B expression had shortened overall survival. We analyzed the positive correlation between glycolysis and circMAT2B expression in HCC using a maximum standardized uptake value determined by preoperative positron emission tomography/computed tomography scanning combined with high‐performance liquid chromatography assessment of the metabolites of glycolysis and the citric acid cycle. The effect of circMAT2B on glycolysis was validated in vitro and in vivo under hypoxic (1% O2) conditions. Functional assays were performed in HCC cells, HCC organoids, and nude mice to explore the tumor‐promoting roles of circMAT2B in HCC. Biotin‐coupled probe pull‐down assays, biotin‐coupled microRNA capture, luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to confirm the interaction among different RNAs. Mechanistically, we demonstrated that circMAT2B up‐regulated expression levels of the microRNA (miR)‐338‐3p target gene PKM2, which encodes a key enzyme in the process of glycolysis, through “sponging” miR‐338‐3p; thus, glycolysis and HCC progression are promoted through this mechanism. Conclusion: CircMAT2B promoted HCC progression by enhanced glycolysis by activating the circMAT2B/miR‐338‐3p/PKM2 axis under hypoxia, which may provide a therapeutic target for HCC.
Implementing and enforcing a smoke‐free policy and by‐law on hospital grounds at Central Coast Local Health District
Authors: Giles Luke , Bauer Lyndon
Published: April 2019

Issue addressed

Smoking by patients, staff and visitors on the grounds of Central Coast Local Health District (CCLHD).

Methods

NSW Health introduced a smoke‐free buildings and vehicles policy in 1988. A smoke‐free grounds policy was implemented in 1999, and a smoke‐free by‐law adopted by CCLHD in 2013, making smoking on CCLHD grounds an offence. Smoking in high‐profile areas near hospital entrances was counted regularly since 2000. Several methods for communicating, monitoring and enforcing these smoke‐free interventions have been adopted, including signage, Public Address announcements and enforcement patrols to ensure by‐law compliance and to issue fines where required. Compliance with the smoke‐free interventions has been supported with the availability of Nicotine Replacement Therapy for patients and visitors.

Results

When monitoring counts first commenced in 2000, smoking rates in high‐profile areas were 8.1% at Gosford Hospital and 11.1% at Wyong Hospital. Counts conducted in 2018 indicated a substantial improvement, with the smoking rate in high‐profile areas reducing to 0.25% at Gosford Hospital and 0.5% at Wyong Hospital. Smoking rates in high‐profile areas have held steady at approximately 0.3% since 2014, after the by‐law was implemented.

Conclusions

The introduction of the smoke‐free by‐law added extra impetus to efforts to reduce smoking on CCLHD hospital grounds by providing the option to fine people who breach the by‐law. Smoking in high‐profile areas has declined substantially since 2011, and is minimal since the establishment of the smoke‐free by‐law.

So what?

The experiences of CCLHD in implementing the smoke‐free by‐law may provide insights for other health services looking to use a similar intervention at their facilities. There are also methodological lessons for other organisations looking to communicate, monitor and enforce smoke‐free policies, without enforcing fines.
Numerical illustrations of 3D tangent hyperbolic liquid flow past a bidirectional moving sheet with convective heat transfer at the boundary
Authors: Kumar Kondlalli Ganesh , Manjunatha Sarpabhushana , Gireesha Bijjanal Jayappa , Abbasi Fahad Munir , Shehzad Sabir Ali
Published: April 2019

Convective heat transfer plays a central role in the numerous industrial devices because it perturbs the mechanical behavior of a system along with its thermodynamics. Keeping such applications in mind, analysis of heat transportation in three‐dimensional tangent hyperbolic fluid flow is investigated here. Convective heat transportation at the boundaries is considered. Rosseland's approximation has been used for the radiation effects. Closed form analytical solutions for the governing equations are difficult to obtain even after the use of similarity transformations. Therefore, the numerical solutions are presented through the Runge‐Kutta‐Fehlberg forth‐fifth method. Graphical analysis of the numerical results has been carried out. Roles of sundry constraints on flow are studied. It is also noted that the rates of heat transportation and skin‐friction are higher in the presence of convective heat transfer near the boundary.
Highly polydisperse keratin rich nanofibers: Scaffold design and in vitro characterization
Authors: Cruz‐Maya Iriczalli , Guarino Vincenzo , Almaguer‐Flores Argelia , Alvarez‐Perez Marco A. , Varesano Alessio , Vineis Claudia
Published: April 2019

The use of bioactive proteins such as keratin has been successfully explored to improve the biological interface of scaffolds with cells during the tissue regeneration. In this work, it is optimized the fabrication of nanofibers combining wool keratin extracted by sulfitolysis, with polycaprolactone (PCL) in order to design bicomponent fibrous matrices able to exert a self‐adapting pattern of signals—morphological, chemical, or physical—confined at the single fiber level, to influence cell and bacteria interactions. It is demonstrated that the blending of highly polydisperse keratin with PCL (50:50) improves the stability of the electrospinning process, promoting the formation of nanofibers—144.1 ± 43.9 nm—without the formation of defects (i.e., beads, ribbons) typically recognized in the fabrication of keratin ones. Moreover, keratin drastically increases the fiber hydrophilicity—compared with PCL fiber alone—thus improving the hMSC adhesion and in vitro proliferation until 14 days. Moreover, the growth of bacterial strains (i.e., Escherichia coli and Staphylococcus aureus) seems to be not specifically inhibited by the contribution of keratin, so that the integration of further selected compounds (i.e., metal ions) is suggested to more efficiently fight against bacteria resistance, to make them suitable for the regeneration of different interfaces and soft tissues (i.e., skin and cornea). © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1803–1813, 2019.
Biophysical study on the interaction of cartap hydrochloride and hemoglobin: Heme degradation and functional changes of protein
Authors: Emadi Mahdieh , Maghami Parvaneh , Khorsandi Khatereh , Hosseinzadeh Reza
Published: April 2019

Cartap hydrochloride is a mildly perilous insecticide known as “Padan” which is used largely in agricultural farms to control weevil and caterpillars. The over use of cartap causes harmful effects on human health. Since the blood may acts as a target and carrier for insecticides, the effect of these compounds on blood in mammalian toxicology is very important. Hemoglobin is a tetramer protein that play critical role in oxygen transport. The aim of this study was to analyze and compare the function and structural changes of hemoglobin in the presence of different concentrations of cartap by employing different spectroscopic techniques. The obtained results show that cartap has a high hemolytic effect which is increased with cartap concentration and reduces the thermal midpoint of hemoglobin. Fluorescence measurements reveal heme degradation at different concentrations of cartap. In consequence of theoretical and experimental results, cartap has an undesirable effect on hemoglobin structure and function.
Involvement of ABC transporters in the efflux and toxicity of MPA‐COOH‐CdTe quantum dots in human breast cancer SK‐BR‐3 cells
Authors: Huang Gui , Wang Lei , Zhang Xiaoying
Published: April 2019

This paper aimed to study the possible involvement of adenosine triphosphate‐binding cassette (ABC) transporters in the detoxification of quantum dots (QDs) in human breast carcinoma (SK‐BR‐3) cells. The effects of QD sizes on such interactions were also evaluated. For this purpose, we used monodispersed MPA‐COOH‐CdTe QDs with different diameters (emission length at 560 and 625 nm, named as QD‐560 and QD‐625). Such QDs tended to accumulate in cells and cause significant toxicity. Using specific inhibitors of ABC transporters, the cellular accumulation and toxicity of QDs in SK‐BR‐3 cells were significantly affected. Moreover, treatment of QDs caused concentration‐ and time‐dependent induction of ABC transporters. Furthermore, the induction effects of smaller QDs were found to be greater than larger ones at equivalent concentrations, suggesting a size‐dependent recognition of substrates by ABC transporters. Overall, these results provided important support for the modulation of QDs toxicity by ABC transporters.
Clinical features and treatment outcome of elderly multiple myeloma patients with impaired renal function
Authors: Chen Jin , Liu Hui , Li Lijuan , Liu Zhaoyun , Song Jia , Wang Guojin , Wang Huaquan , Ruan Erbao , Ding Kai , Shao Zonghong , Fu Rong
Published: April 2019

Background

Renal impairment (RI) is a most common complication of multiple myeloma (MM), which is associated with an increased risk of early death and worse survival.

Methods

We retrospectively analyzed clinical features and outcomes of 77 MM patients over 70 years old and compared the differences between with and without RI groups.

Results

The percentage of elder MM patients with RI was 61%. Hemoglobin level was a protective factor (OR = 0.954, P = 0.033), while creatinine and hypertension were hazards (OR = 1.288, P < 0.001 and OR = 30.12, P = 0.008). And the percentages of patients with mild‐to‐moderate RI and moderate‐to‐severe RI were 40.4% and 59.6%. Complete remission (CR) rate was higher in patients treated with bortezomib (33.3%) than those with non‐bortezomib treatment (3.33%) (P = 0.007). Meanwhile, CRrenal was higher in patients with bortezomib (58.3%) than non‐bortezomib treatment (22.2%) (P = 0.025). The median OS of the patients with RI treated with bortezomib was longer than those with non‐bortezomib regimens (15.0 vs 6.0 months, P = 0.001). The same result was observed in the patients with moderate‐to‐severe RI (13.0 vs 6.0 months, P = 0.007). The median OS of the patients with RI receiving the bortezomib regimens (15 months) was longer than those with non‐bortezomib regimens (6.0 months) (P = 0.001).

Conclusion

Hemoglobin is a protective factor in elder patients with RI, while creatinine and hypertension were hazards. The median OS of elderly patients with RI was worse, and bortezomib can improve the CR rate in these patients.
Cognitive‐behavioral therapy (CBT) for generalized anxiety disorder: Contrasting various CBT approaches in a randomized clinical trial
Authors: Stefan Simona , Cristea Ioana A. , Szentagotai Tatar Aurora , David Daniel
Published: April 2019

Objective

Cognitive‐behavior therapy (CBT) is considered the “golden standard” psychotherapy for generalized anxiety disorder (GAD) but, at this point, we have little information about differences among various CBT approaches.

Method

We conducted a randomized controlled trial to compare three CBT protocols for GAD: (a) Cognitive Therapy/Borkovec's treatment package; (b) Rational Emotive Behavior Therapy, and (c) Acceptance and Commitment Therapy/Acceptance‐based behavioral therapy. A number of 75 patients diagnosed with GAD, aged between 20 and 51 (m = 27.13; standard deviation = 7.50), 60 women and 11 men, were randomized to the three treatment arms.

Results

All treatments were associated with large pre‐post intervention reductions in GAD symptoms and dysfunctional automatic thoughts, with no significant differences between groups. Correlation analyses showed similar associations between changes in symptoms and changes in dysfunctional automatic thoughts.

Conclusions

All three approaches appear to be similarly effective. Implications for the theoretical models underlying each of the three cognitive‐behavior therapy approaches are discussed.
The evolution of our understanding and treatment of eating disorders over the past 50 years
Authors: Marks Andrea
Published: April 2019

Although historical descriptions date back to the Hellenistic era, and Gull's naming of anorexia nervosa as a medical disorder to the late 19th century, it is only in the past 50 years that eating disorders have become widely recognized as the prevalent, potentially fatal, complex, and confounding biopsychosocial illnesses we confront today. This paper reviews the considerable advancements in our knowledge of eating disorders during three time periods: the “early years” of the 1960s and 1970s; the “middle years” of the 1980s and 1990s; and the 21st century to date. The recent Diagnostic and Statistical Manual of Mental Disorders, 5th Edition describes six major feeding and eating disorders. This historical focus addresses the interaction of multiple factors contributing to the incidence, primarily of anorexia nervosa and bulimia nervosa, in vulnerable individuals, and efforts to develop effective treatment strategies and programs in a variety of settings. Future challenges are also addressed.
Compulsory treatment in eating disorders: Control, provocation, and the coercion paradox
Authors: Túry Ferenc , Szalai Tamás , Szumska Irena
Published: April 2019

In eating disorders, the denial of the illness is a central phenomenon. In the most severe forms of anorexia, compulsory treatment may be necessary. The professional acceptance of involuntary treatment is controversial due to the fact that the autonomy of the patient is juxtaposed with the obligation of the health care practitioner to save lives. This paper discusses the major practical and ethical considerations surrounding this controversy. In addition, case vignettes are used to illustrate various strategies to diminish client resistance and enhance motivation toward treatment. Involving the family is nearly always essential for the treatment of patients with eating disorders. In some cases, parental consultation (i.e., treatment without the client) can also be an option. Home visits, though rarely used, can reframe the therapeutic relationship and provide information about family functioning. In general, a lower level of treatment coercion can be achieved through transparent client‐parent and client‐therapist communication.
Low‐dose aspirin reduces hypoxia‐induced sFlt1 release via the JNK/AP‐1 pathway in human trophoblast and endothelial cells
Authors: Lin Li , Li Guanlin , Zhang Wanyi , Wang Yan‐Ling , Yang Huixia
Published: April 2019

Pre‐eclampsia (PE) is a serious hypertensive disorder of pregnancy that remains a leading cause of perinatal and maternal morbidity and mortality worldwide. Placental ischemia/hypoxia and the secretion of soluble fms‐like tyrosine kinase 1 (sFlt1) into maternal circulation are involved in the pathogenesis of PE. Although low‐dose aspirin (LDA) has beneficial effects on the prevention of PE, the exact mechanisms of action of LDA, particularly on placental dysfunction, and sFlt1 release, have not been well investigated. This study aimed to determine whether LDA exists the protective effects on placental trophoblast and endothelial functions and prevents PE‐associated sFlt1 release. First, we observed that LDA mitigated hypoxia‐induced trophoblast apoptosis, showed positive effects on trophoblast cells migration and invasion activity, and increased the tube‐forming activity of human umbilical vein endothelial cells (HUVECs). In addition, LDA decreased hypoxia‐induced sFlt1 production, and the c‐Jun NH2‐terminal kinase/activator protein‐1 (JNK/AP‐1) pathway was shown to mediate the induction of sFlt1. Moreover, the transcription factor AP‐1 was confirmed to regulate the Flt1 gene expression by directly binding to the Flt1 promoter in luciferase assays. The result of chromatin immunoprecipitation assays further demonstrated that LDA could directly decrease the expression of the transcription factor AP‐1, and thus decrease sFlt1 production. Finally, the effects of LDA on sFlt1 production were proved in human placental explants. Taken together, our data show the protective effects of LDA against trophoblast and endothelial cell dysfunction and reveal that the LDA‐mediated inhibition of sFlt1 via the JNK/AP‐1 pathway may be a potential cellular/molecular mechanism for the prevention of PE.
Long noncoding RNA C2dat1 protects H9c2 cells against hypoxia injury by downregulating miR‐22
Authors: Sun Huan , Shi Kaiyao , Xie Di , Zhang Hongli , Yu Bo
Published: April 2019

Myocardial ischemia is accompanied with hypoxia injury in myocardial cells. Long noncoding RNAs (lncRNA) CAMK2D‐associated transcript 1 (C2dat1) C2dat1) has been linked with several ischemic diseases. However, the investigation regarding its role in myocardial ischemia is relatively rare. The aim of this study was to examine the role of C2dat1 in hypoxia response in H9c2 cells. H9c2 cells were subjected to hypoxia to evoke cell damage. Expressions of C2dat1, miR‐22, and VEGF in H9c2 cells were altered by transfection, and then cell survival, migration, and invasion were respectively assessed posttransfection. Regulatory relationship between C2dat1, miR‐22, and VEGF, as well as the involvement of PI3K/AKT/mTOR and JAK/STAT3 pathways in H9c2 cells injury was then studied. C2dat1 upregulation ameliorated hypoxia injury in H9c2 cells due to the increased viability, migration, and invasion, as well as the decreased apoptosis. miR‐22 was negatively regulated by C2dat1. The effects of C2dat1 on H9c2 cells injured by hypoxia were attenuated when miR‐22 was overexpressed. VEGF was a target gene of miR‐22, and VEGF exerted similar protective effects to C2dat1. Finally, we found that silence of C2dat1 deactivated PI3K/AKT/mTOR and JAK/STAT3 pathways via regulating miR‐22 and its downstream gene VEGF. C2dat1‐miR‐22‐VEGF axis could regulate hypoxia injury in H9c2 cells. C2dat1 alleviated hypoxia injury possibly via downregulating miR‐22, then upregulating VEGF, which further enhancing the activation of PI3K/AKT/mTOR and JAK/STAT3 pathways.
Combinational therapy of lithium and human neural stem cells in rat spinal cord contusion model
Authors: Mohammadshirazi Atiyeh , Sadrosadat Hoda , Jaberi Razieh , Zareikheirabadi Masoomeh , Mirsadeghi Sara , Naghdabadi Zahra , Ghaneezabadi Mahdieh , Fardmanesh Mehdi , Baharvand Hossein , Kiani Sahar
Published: April 2019

A large number of treatment approaches have been used for spinal cord injury improvement, a medically incurable disorder, and subsequently stem cell transplantation appears to be a promising strategy. The main objective of this study is to ascertain whether combinational therapy of human neural stem cells (hNSCs) together with lithium chloride improves cell survival, proliferation, and differentiation in a rat spinal contusion model, or not.

Contusive spinal cord injury was implemented on Wistar male rats. Experimental groups comprised of: control, hNSCs transplanted, lithium chloride (Li), and hNSCs and lithium chloride (hNSCs + Li). In every experimental group, locomotor activity score and motor evoked potential (MEP) were performed to evaluate motor recovery as well as histological assessments to determine mechanisms of improvement.

In accordance with our results, the hNSCs + Li and the Li groups showed significant improvement in locomotor scores and MEP. Also, Histological assessments revealed that transplanted hNSCs are capable of differentiation and migration along the spinal cord. Although NESTIN‐positive cells were proliferated significantly in the Lithium group in comparison with control and the hNSCs + Li groups, the quantity of ED1 cells in the hNSCs + Li was significantly larger than the other two groups.

Our results demonstrate that combinational therapy of hNSCs with lithium chloride and lithium chloride individually are adequate for ameliorating more than partial functional recovery and endogenous repair in spinal cord‐injured rats.
New potentials for 3‐hydroxy‐3‐methyl‐glutaryl‐coenzymeA reductase inhibitors: Possible applications in retarding diabetic complications
Authors: Bahrambeigi Saman , Rahimi Mahdi , Yousefi Bahman , Shafiei‐Irannejad Vahid
Published: April 2019

The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid‐lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid‐lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti‐inflammatory, and antiproliferative properties beyond their lipid‐lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications.