bluuebunny/crossref_metadata_2025_split huggingface dataset:
The epileptic encephalopathy jungle – from Dr West to the concepts of aetiology-related and developmental encephalopathies
Authors: Kalser Judith , Cross J Helen 
Published: January 2018

Purpose of review
We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy.

Recent findings
The concept of ‘epileptic encephalopathy’ has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of ‘developmental encephalopathy’ which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful.

Summary
The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.
Metagenomic analysis uncovers strong relationship between periodontal pathogens and vascular dysfunction in American Indian population
Authors: Vijay Kumar Prathik K , Gottlieb Roberta A. , Lindsay Suzanne , Delange Nicole , Penn Tanya E. , Calac Dan , Kelley Scott T. 
Published: January 2018

AbstractPeriodontal disease (PD) is a well-known risk factor for cardiovascular disease (CVD) but the casual relationship is unclear. American Indians/Alaskan Natives (AI/AN) have high rate of both PD and CVD and a better understanding of how PD might affect heart health would be particularly helpful in this population. In this study, we sequenced the bacterial biofilms of periodontal (gum) pockets and used metagenomic sequencing and vascular health measurements (immune cytokine profiles and vascular flow) to determine the relationship of microbial pathogens and CVD. Twelve subjects were sequenced before and after standard periodontal treatment. Other measures taken before and after treatment included a full dental screening; serum concentration of key immune cytokines from blood samples; lipid profiles from fasting venous blood; and plasma glucose concentrations. The non-invasive Laser Doppler Fluxmetry (LDF) procedure was conducted to measures the microvascular vasodilation. We found highly significant relationships between the total abundance of 4 periodontal pathogens,Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia and Treponema denticola, and the inflammatory cytokine interleukin 1 beta (IL-1β) (r=0.63; p=0.009) as well as with vascular flow post sodium nitroprusside (SNP) treatment (r=p=0.006). Two bacterial species that correlated most with IL-1β wereF. nucleatum and P. gingivalis. IL-1β has been strongly implicated as a causal factor in atherosclerosis and in periodontal bone loss. To our knowledge, this is the first direct link between abundance of specific periodontal pathogens and cardiovascular disease in humans, and suggests that these pathogens could be used as warning signs for cardiovascular risk.
The Chlamydia type III effector TarP alters the dynamics and organization of host cell focal adhesions
Authors: Pedrosa António T. , Murphy Korinn N. , Nogueira Ana T. , Brinkworth Amanda J. , Thwaites Tristan R. , Aaron Jesse , Chew Teng-Leong , Carabeo Rey A. 
Published: January 2018

AbstractThe human pathogen Chlamydia trachomatis targets epithelial cells lining the genital mucosa. We observed that infection of various cell types, including fibroblasts and epithelial cells resulted in the formation of unusually stable focal adhesions that resisted disassembly induced by the myosin II inhibitor, blebbistatin. Super-resolution microscopy revealed in infected cells the vertical displacement of paxillin and FAK from the signaling layer of focal adhesions; while vinculin remained in its normal position within the force transduction layer. The candidate type III effector TarP which localized to focal adhesions during infection and when expressed ectopically, was sufficient to mimic both the reorganization and blebbistatin-resistant phenotypes. These effects of TarP, including its localization to focal adhesions required interaction with the host protein vinculin through a specific domain at the C-terminus of TarP. The consequence of Chlamydia-stabilized focal adhesions was restricted cell motility and enhanced attachment to the extracellular matrix. Thus, via a novel mechanism, Chlamydia inserts TarP within focal adhesions to alter their organization and dynamics.
Generation of a novel growth-enhanced and reduced environmental impact transgenic pig strain
Authors: Zhang Xianwei , Li Zicong , Yang Huaqiang , Liu Dewu , Cai Gengyuan , Li Guoling , Mo Jianxin , Wang Dehua , Zhong Cuili , Wang Haoqiang , Sun Yue , Shi Junsong , Zheng Enqin , Meng Fanming , Zhang Mao , He Xiaoyan , Zhou Rong , Zhang Jian , Huang Miaorong , Zhang Ran , Li Ning , Zhe Fanming , Yang Jinzeng , Wu Zhenfang 
Published: January 2018

ABSTRACTIn pig production, insufficient feed digestion causes excessive nutrients such as phosphorus and nitrogen, which are then released to the environment. To address the issue of environmental emissions, we have established transgenic pigs harboring a single-copy quad-cistronic transgene and simultaneously expressing three microbial enzymes, β-glucanase, xylanase, and phytase in the salivary glands. All the transgenic enzymes were successfully expressed, and the digestion of non-starch polysaccharides (NSPs) and phytate in the feedstuff was enhanced. Fecal nitrogen and phosphate outputs were reduced by 23%–46%, and growth rate improved by 23.4% (gilts) and 24.4% (boars) when the pigs were fed on a corn and soybean-based diet and high-NSP diet. The transgenic pigs showed a 11.5%– 14.5% improvement in feed conversion rate compared to the age-matched wild-type littermates. These findings indicate that transgenic pigs are promising resources for improving feed efficiency and reducing nutrient emissions to the environment.
Prediction of Accurate Binding Modes using Combination of classical and accelerated Molecular dynamics and Free Energy Perturbation Calculations: An Application to Toxicity Studies
Authors: Fratev Filip , Steinbrecher Thomas , Jónsdóttir Svava Ósk 
Published: January 2018

AbstractEstimating the correct binding modes of ligands in protein-ligand complexes is not only crucial in the drug discovery process, but also for elucidating potential toxicity mechanisms. In the current paper, we discuss and demonstrate a computational modelling protocol using the combination of docking, classical (cMD) and accelerated (aMD) molecular dynamics and free energy perturbation (FEP+ protocol) for identification of the binding modes of selected perfluorocarboxyl acids (PFCAs) in the PPARγ nuclear receptor.Initially, we employed both the regular and induced fit docking which failed to correctly predict the ligand binding modes and rank the compounds with respect to experimental free energies of binding, when they were docked into non-native X-ray structure. The cMD and aMD simulations identified the presence of multiple binding modes for these compounds, and the shorter chain PFCAs (C6-C8) continuously moved between a few energetically favourable binding conformations. These results demonstrate that the docking scoring function cannot rank compounds precisely in such cases, not due to its insufficiency, but because of the use of incorrect or only one unique bindings pose, neglecting the protein dynamics. Finally, based on MD predictions of binding conformations, the FEP+ sampling protocol was extended and then accurately reproduced experimental differences in the free energies. Thus, the preliminary MD simulations can also provide helpful information about correct set-up of the FEP+ calculations. These results show that the PFCAs binding modes were accurately predicted and the FEP+ protocol can be used to estimate free energies of binding of flexible molecules outside of typical drug-like compounds.Our in silico workflow revealed the main characteristics of the PFCAs, which are week PPARγ partial agonists and illustrated the importance of specific ligand-residue interactions within the LBD. This work also suggests a common workflow for identification of ligand binding modes, ligand-protein dynamics description and relative free energy calculations.
Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
Authors: Kumar Binod , Rosenberg Avi Z. , Choi Su Mi , Fox-Talbot Karen , De Marzo Angelo M. , Nonn Larisa , Brennen W. Nathaniel , Marchionni Luigi , Halushka Marc K. , Lupold Shawn E. 
Published: January 2018

ABSTRACTMiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. MiR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.
Irreversible temperature gating in trpv1 sheds light on channel activation
Authors: Sánchez-Moreno Ana , Guevara-Hernández Eduardo , Contreras-Cervera Ricardo , Rangel-Yescas Gisela , Ladrón-de-Guevara Ernesto , Rosenbaum Tamara , Islas León D. 
Published: January 2018

AbstractTemperature activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of information, including several experimentally determined structural models of TRP channels, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. This inactivation is associated with specific conformational changes in the membrane proximal domain. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening.
Drivers of the formation of e-loyalty towards tourism destinations
Authors: Parra-Lopez Eduardo , Martínez-González José Alberto , Chinea-Martin Angel 
Published: January 2018

PurposeThe purpose of this paper is to determine the drivers of the formation of e-loyalty in a tourist destination, providing a model composed of variables that are under the control of the firm along with others that are not fully controllable by professionals.Design/methodology/approachThe study was carried out with a sample of 497 subjects, university students and online consumers, and with the use of structural equations (partial least squares).FindingsResults show that young people give a high valuation to all the variables used in the research. These results contribute to the literature on e-loyalty in tourism destinations and improve tourism loyalty in this population segment.Research limitations/implicationsThe main limitation of this research has been related to the number of variables and measurement indicators that, according to the literature review, influence e-loyalty. Finally, a balanced and statistically significant model has been developed that has practical utility and analyzes online purchase of tourism products from a process perspective that includes variables that are internal and external to the firm.Practical implicationsThe study suggests that young people have a favourable attitude and predisposition towards e-commerce, which, in turn, favours firms’ efforts to promote consumption and loyalty within the framework of the model’s variables.Originality/valueThis research paper has important value by analysing the initiating variables to determine how e-loyalty can be managed in tourist destinations, in addition to analysing an important segment for future tourism development.
The development of neonatal nursing standards of practice for Cambodia: a Delphi study
Authors: Prak Manila , Wivatvanit Suvinee 
Published: January 2018

Purpose
Cambodia has one of the highest death rates for children under five years of age in Southeast Asia. The high mortality rate of children under five years of age, especially the neonate is 35 per 1,000 for the period zero to four years. There are no neonatal nursing standards of practice to guide nurses providing neonatal nursing care. Some general guidelines are currently being implemented for both doctors and nurses. The Minister for Health officially launched the Cambodian Council of Nurses’ Guideline for the Standard of Nursing Care in December 2015. In the absence of specific neonatal nursing standards of practice, the purpose of this paper is to develop the Neonatal Nursing Standard of Practice for Cambodia.

Design/methodology/approach
The Delphi technique was selected as being appropriate for this study. The snowball with purposive sampling was used. The identified experts were located across Cambodia so the e-Delphi approach was considered appropriate and applicable according to the study context. Four experts preferred to be interviewed face-to-face, while 16 experts were confident to use e-mail to respond to the questionnaire in Round 1. In total, 19 experts provided responses via e-mail to the Rounds 2 and 3 questionnaires.

Findings
A Standard for Neonatal Nursing Practice for Cambodia which consists of ten standards was found as a result of this study: assessment, nursing diagnosis, planning, implementation, evaluation, ethics, evidence-based practice and research, health teaching and health promotion, continuing education, and communication.

Originality/value
All items and sub-items achieved consensus as either being at the most significant level and therefore, could be key indicators for neonatal nursing standards of practice. The results of this study can be incorporated into a focused discussion led by the Nursing and Midwifery Bureau of the Ministry of Health to develop national standards of practice for neonatal nurses in Cambodia.
Impact of a new simplified disability scoring system for adult patients with localized scleroderma
Authors: Okiyama Naoko , Asano Yoshihide , Hamaguchi Yasuhito , Jinnin Masatoshi , Motegi Sei‐ichiro , Koizumi Haruka , Hasegawa Minoru , Ishikawa Osamu , Sato Shinichi , Takehara Kazuhiko , Yamamoto Toshiyuki , Fujimoto Manabu , Ihn Hironobu 
Published: January 2018

AbstractLocalized scleroderma (LoS) involves dermal but not internal inflammation and fibrosis. Cosmetic changes often impact quality of life (QOL), however, impairment of activities of daily living (ADL) in LoS patients has not been investigated. To determine what factor(s) are associated with ADL in adult patients with LoS, we performed a retrospective observational study in 177 Japanese adult LoS patients using a novel LoS disability score based on Barthel's indices of ADL: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility and stairs. LoS disability scores increased in proportion to the number of affected body parts but were not correlated to age and duration of illness. The presence of leg lesions significantly impaired ADL of LoS patients compared with lesions on other body parts. Patients treated with systemic medications, who tended to have multiple lesions, presented higher LoS disability scores than those without systemic treatments. Our study proposes that physicians evaluate ADL, not only QOL, in LoS patients. Our findings using LoS disability scoring indicate that multiple affected body parts and leg lesions are risk factors for ADL impairment.
Efficacy of Peracetic Acid in Inactivating Foodborne Pathogens on Fresh Produce Surface
Authors: Singh Prashant , Hung Yen‐Con , Qi Hang 
Published: January 2018

AbstractWashing treatment with effective sanitizer is one of the critical steps in ensuring fresh produce safety. This study was to evaluate the efficacy of peracetic acid (PAA; VigorOx® 15 F&V), chlorine‐based sanitizers (acidic electrolyzed water [AEO], near neutral electrolyzed water and bleach), lactic acid, and deionized (DI) water to reduce Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella Typhimurium DT104 from fresh produce surfaces. A 5‐strain cocktail of E. coli O157:H7, L. monocytogenes, and S. Typhimurium DT104 was separately prepared and used for surface inoculation on produce samples (E. coli O157:H7 on romaine lettuce, lemons, tomatoes, and blueberries; L. monocytogenes on romaine lettuce and cantaloupe; S. Typhimurium DT104 on lemons, tomatoes, cantaloupe, and blueberries). PAA at 45, 85, and 100 mg/L; AEO, NNEO, and bleach at 100 mg/L of free chlorine; lactic acid at 2%; and DI water were used for washing inoculated produce in an automated produce washer for 5 min. In general, PAA at 100 mg/L achieved the highest microbial inactivation of E. coli O157:H7 (lettuce, lemon, tomato, and blueberry at 2.2, 5.7, 5.5, and 6.7 log CFU/g, respectively), S. Typhimurium DT104 (lemon, tomato, cantaloupe, blueberry at 5.4, 6.8, 4.5, and 5.9 log CFU/g, respectively), and L. monocytogenes (lettuce and cantaloupe at 2.4 and 4.4 log CFU/g, respectively). Efficacy of sanitizers on produce with coarse surface (for example, lettuce and cantaloupe) was lower than produce with smooth texture (lemon, tomato, and blueberry). Cross‐contamination of E. coli O157:H7 among romaine lettuce heads during simulated retail crisping process was greatly reduced by the application of PAA and NNEO.Practical ApplicationNNEO and PAA showed high efficacy in foodborne pathogen removal from fresh produce. Produce surface texture plays an important role in pathogen removal. NNEO and PAA effectively prevented cross‐contamination during the crisping process.
Lipopolysaccharide‐induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood
Authors: Fricke Erin M. , Elgin Timothy G. , Gong Huiyu , Reese Jeff , Gibson‐Corley Katherine N. , Weiss Robert M. , Zimmerman Kathy , Bowdler Noelle C. , Kalantera Karen M. , Mills David A. , Underwood Mark A. , McElroy Steven J. 
Published: January 2018

ProblemPremature birth complicates 10%‐12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)‐induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine.Method of studyPregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 μg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis.ResultsMaternal injection with LPS caused elevated IL‐1β, IL‐10, IL‐6, KC‐GRO, and TNF. Placental tissue showed increased IL‐1β, IL‐6, and KC‐GRO and decreased IL‐10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS‐induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring.ConclusionLipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period.
Intravitreal diclofenac for treatment of refractory uveitis‐associated cystoid macular oedema: A before and after clinical study
Authors: Kianersi Farzan , Rezaeian‐Ramsheh Abdolreza , Pourazizi Mohsen , Kianersi Hamidreza 
Published: January 2018

AbstractBackgroundCystoid macular oedema (CME) is one of the important complications of uveitis leading to irreversible blindness. Currently, there is no gold standard treatment for this condition. The aim of this study was to investigate the effects of single intravitreal diclofenac (IVD) injection on short‐term outcome of refractory uveitis‐associated CME.MethodsThis was a prospective clinical study on 16 consecutive patients (16 eyes) with refractory uveitis‐associated CME. Intravitreal injection of 500 μg/0.1 ml of diclofenac sodium was given to the patients. The clinical outcomes considered were best‐corrected visual acuity (BCVA) change and central macular thickness (CMT) changes in the pre‐ and postinjection periods. Follow‐up examinations were performed at 1 and 4 weeks after the injection.ResultsAge of the patients varied from 18 to 59 years (mean ± SD: 39.5 ± 13.2 years). Ten patients (62.5%) were females. Statistically significant differences were found in the decrease of mean BCVA (logMAR) (p = 0.043) and mean CMT (p = 0.003) during the study period. There was no significant difference in the intraocular pressure (IOP) increase at the end of the study (p = 0.94).ConclusionIntravitreal diclofenac (IVD) may be a promising treatment for refractory uveitis‐associated CME. Further clinical trials with a larger sample size should be conducted to confirm these findings and compare them with other treatments.