bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Back Pain and Its Associated Factors among Nurses in Public Hospitals of Penang, Malaysia
Authors: Ibrahim Mohd Ismail , Zubair Izani Uzair , Yaacob Najib Majdi , Ahmad Mohd Izmi , Shafei Mohd Nazri
Published: November 2019

Objectives: To determine the prevalence of low back pain (LBP) and its associated factors among the nurses working in the public hospitals of Penang, Malaysia. Methods: A cross-sectional study was conducted on nurses, aged 25–60 years, who had been working for at least three months at six public hospitals of Penang. A proportionate stratified random sampling method was applied to select 1292 respondents. The Malay-validated BACKS Tool questionnaire using a 5-point Likert scale was used to obtain data. Simple and multiple logistic regression analyses were performed. Results: A total of 989 (76.5%) nurses suffered from LBP at a point of time. The factors significantly associated with LBP among the nurses included working more than seven hours [adjusted odds ratio (AOR) (95% confidence interval (CI)) 1.48 (1.06, 1.98)], twisting of the body while working [AOR (95% CI) 1.60 (1.13, 2.26)], manual handling of patients in wards [AOR (95% CI) 1.44 (1.08, 2.07)], and fatigue [AOR (95% CI) 2.63 (1.94, 3.58)]. Conclusion: The prevalence of LBP among the nurses in the public hospitals of Penang was relatively high. The factors predicting LBP included working more than seven hours a day, twisting of the body while working, manual handling, and fatigue. The findings from this study may better enable policymakers to devote resources to minimize low back pain among nurses. The nurses should be encouraged to comply with safe working procedures.
Health Care Needs in School-Age Refugee Children
Authors: Hjern Anders , Kling Stefan
Published: November 2019

Most European countries have systematic health assessments of refugees with a main focus on infectious diseases. The aim of this study was to describe the broader health care needs identified in newly settled refugee children in a school health setting. The study population consisted of all 609 recently settled Non-European refugee and asylum-seeking children in the age range 6–15 years who were enrolled in the schools of Malmö, Sweden during the autumn semester of 2015, of which 265 had arrived in Sweden unaccompanied. The data were collected in a structured routine intake interview by an experienced school nurse. Almost half of the children had obvious untreated caries. For the unaccompanied children, prominent mental health needs were present in almost one in three. Previously unidentified vision and/or hearing problems were identified in one in ten and around 5% had a daily medication, and 4.5% of the unaccompanied children and 1.2% of the accompanied children were judged to be in need of immediate care and were referred accordingly. Newly settled refugee children in northern Europe have considerable health care needs apart from communicable diseases. School health services have a unique platform to identify and initiate this care.
Exploring the Bi-Directional Association between Tobacco and E-Cigarette Use among Youth in Canada
Authors: Aleyan Sarah , Gohari Mahmood R. , Cole Adam G. , Leatherdale Scott T.
Published: November 2019

Research has demonstrated associations between e-cigarette use and tobacco use among youth. However, few studies have examined whether reciprocal relationships exist between e-cigarette and tobacco use. The objective of this study was to examine whether bi-directional associations exist between e-cigarette and tobacco use in a large longitudinal sample of Canadian youth. A longitudinal sample of secondary students (n = 6729) attending 87 schools in Ontario and Alberta, Canada, who completed the COMPASS student questionnaire across three waves (from 2014–2015 to 2016–2017) was identified. Using cross-lagged models, we explored bi-directional associations between current tobacco and e-cigarette use, adjusting for relevant covariates. Our findings showed that current e-cigarette use predicted subsequent tobacco use between Wave 1 (W1) and Wave 2 (W2) of the study (W1–2: OR = 1.54, 95% CI = 1.37–1.74). Similarly, current tobacco use predicted e-cigarette use during earlier waves of the study (W1–2: OR = 1.43, 95% CI = 1.30–1.58). However, these relationships dissipated in later waves, when tobacco use no longer predicted e-cigarette use (W2–3: OR = 1.07, 95% CI = 0.99–1.16). This study extends prior work that focused mainly on the association between e-cigarette and subsequent tobacco use. Specifically, our findings portray a more complex relationship, where e-cigarette use may influence and be influenced by tobacco use.
Comparing the Influence of Green Credit on Commercial Bank Profitability in China and Abroad: Empirical Test Based on a Dynamic Panel System Using GMM
Authors: Song Xiaoling , Deng Xin , Wu Ruixue
Published: November 2019

This study establishes a dynamic panel model for 12 Chinese-listed commercial banks and seven international commercial banks. More specifically, it examines the impact of green credit on the profitability of commercial banks and the differences between China and other countries while using the generalized method of moments. The research shows that the Equatorial Principles project-financing ratio of international banks positively affects bank profitability, while the ratio of green credit for Chinese commercial banks is inversely related to their profitability. Further, a comparative study of China and other countries highlights that the green credit business is at significantly different stages in China and the rest of the world. This study also finds that the profitability of China’s banking sector is positively affected by asset size, management expense ratio, cash ratio, and GDP growth rate, in addition to the common influencing factor of non-performing loan ratio, whereas asset size and capital adequacy ratio negatively affects the international banking sector. Drawing on these empirical conclusions, this study offers suggestions for the further development of green credit in Chinese commercial banks.
In Vitro Evaluation and Docking Studies of 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde Derivatives as Potential Anti-Alzheimer’s Agents
Authors: Mphahlele Malose J. , Gildenhuys Samantha , Agbo Emmanuel N.
Published: November 2019

A series of novel 2-carbo–substituted 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehydes and their 6-(4-trifluoromethyl)phenylhydrazono derivatives have been prepared and evaluated for biological activity against the human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The most active compounds from each series were, in turn, evaluated against the following enzyme targets involved in Alzheimer’s disease, β-secretase (BACE-1) and lipoxygenase-15 (LOX-15), as well as for anti-oxidant potential. Based on the in vitro results of ChE and β-secretase inhibition, the kinetic studies were conducted to determine the mode of inhibition by these compounds. 2-(4-Methoxyphenyl)-5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde (2f), which exhibited significant inhibitory effect against all these enzymes was also evaluated for activity against the human lipoxygenase-5 (LOX-5). The experimental results were complemented with molecular docking into the active sites of these enzymes. Compound 2f was also found to be cytotoxic against the breast cancer MCF-7 cell line.
The Roles of MicroRNAs (miRNAs) in Avian Response to Viral Infection and Pathogenesis of Avian Immunosuppressive Diseases
Authors: Zhou Linyi , Zheng Shijun J.
Published: November 2019

MicroRNAs (miRNAs) are a class of non-coding small RNAs that play important roles in the regulation of various biological processes including cell development and differentiation, apoptosis, tumorigenesis, immunoregulation and viral infections. Avian immunosuppressive diseases refer to those avian diseases caused by pathogens that target and damage the immune organs or cells of the host, increasing susceptibility to other microbial infections and the risk of failure in subsequent vaccination against other diseases. As such, once a disease with an immunosuppressive feature occurs in flocks, it would be difficult for the stakeholders to have an optimal economic income. Infectious bursal disease (IBD), avian leukemia (AL), Marek’s disease (MD), chicken infectious anemia (CIA), reticuloendotheliosis (RE) and avian reovirus infection are on the top list of commonly-seen avian diseases with a feature of immunosuppression, posing an unmeasurable threat to the poultry industry across the globe. Understanding the pathogenesis of avian immunosuppressive disease is the basis for disease prevention and control. miRNAs have been shown to be involved in host response to pathogenic infections in chickens, including regulation of immunity, tumorigenesis, cell proliferation and viral replication. Here we summarize current knowledge on the roles of miRNAs in avian response to viral infection and pathogenesis of avian immunosuppressive diseases, in particular, MD, AL, IBD and RE.
NtMYB3, an R2R3-MYB from Narcissus, Regulates Flavonoid Biosynthesis
Authors: Anwar Muhammad , Yu Weijun , Yao Hong , Zhou Ping , Allan Andrew C. , Zeng Lihui
Published: November 2019

R2R3-MYB transcription factors play important roles in the regulation of plant flavonoid metabolites. In the current study, NtMYB3, a novel R2R3-MYB transcriptional factor isolated from Chinese narcissus (Narcissus tazetta L. var. chinensis), was functionally characterized. Phylogenetic analysis indicated that NtMYB3 belongs to the AtMYB4-like clade, which includes repressor MYBs involved in the regulation of flavonoid biosynthesis. Transient assays showed that NtMYB3 significantly reduced red pigmentation induced by the potato anthocyanin activator StMYB-AN1 in agro-infiltrated leaves of tobacco. Over-expression of NtMYB3 decreased the red color of transgenic tobacco flowers, with qRT-PCR analysis showing that NtMYB3 repressed the expression levels of genes involved in anthocyanin and flavonol biosynthesis. However, the proanthocyanin content in flowers of transgenic tobacco increased as compared to wild type. NtMYB3 showed expression in all examined narcissus tissues; the expression level in basal plates of the bulb was highest. A 968 bp promoter fragment of narcissus FLS (NtFLS) was cloned, and transient expression and dual luciferase assays showed NtMYB3 repressed the promoter activity. These results reveal that NtMYB3 is involved in the regulation of flavonoid biosynthesis in narcissus by repressing the biosynthesis of flavonols, and this leads to proanthocyanin accumulation in the basal plate of narcissus.
Identifying Metabolic Perturbations and Toxic Effects of Rac-Metalaxyl and Metalaxyl-M in Mice Using Integrative NMR and UPLC-MS/MS Based Metabolomics
Authors: Zhang Ping , Wang Sheng , He Yuhan , Xu Yangyang , Shi Dongmei , Yang Furong , Yu Weizhong , Zhu Wentao , He Lin
Published: November 2019

Although metabolic perturbations are sensitive indicators for low-dose toxic effects, the metabolic mechanisms affected by rac-metalaxyl and metalaxyl-M in mammals from a metabolic profiling perspective remain unclear. In this study, the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M in mice were carefully investigated using integrative nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based metabolomics. Histopathology, NMR-based untargeted urine profile, multivariate pattern recognition, metabolite identification, pathway analysis, UPLC-MS/MS based targeted serum amino acids, and tryptophan pathway analysis were determined after rac-metalaxyl and metalaxyl-M exposure, individually. Histopathology indicated that metalaxyl-M induced greater hepatocellular inflammatory, necrosis, and vacuolation in mice than rac-metalaxyl at the same exposure dosage. The metabolic perturbations induced by rac-metalaxyl and metalaxyl-M were directly separated using partial least-squares discriminant analysis (PLS-DA). Furthermore, metabolite identification and pathway analysis indicated that rac-metalaxyl mainly induced ten urine metabolite changes and four pathway fluctuations. However, metalaxyl-M induced 19 urine metabolite changes and six pathway fluctuations. Serum amino acids and tryptophan pathway metabolite changes induced by rac-metalaxyl and metalaxyl-M were also different even at the same exposure level. Such results may provide specific insight into the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M, and contribute to providing available data for health risk assessments of rac-metalaxyl and metalaxyl-M at a metabolomics level.
Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles
Authors: Zhao Kai , Li Dan , Cheng Guogang , Zhang Baozhen , Han Jinyu , Chen Jie , Wang Baobei , Li Mengxia , Xiao Tianxia , Zhang Jian , Zhou Dongpo , Jin Zheng , Fan Xiujun
Published: November 2019

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.
Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies
Authors: Palumbo Giuseppe Alberto , Parrinello Nunziatina Laura , Giallongo Cesarina , D’Amico Emanuele , Zanghì Aurora , Puglisi Fabrizio , Conticello Concetta , Chiarenza Annalisa , Tibullo Daniele , Di Raimondo Francesco , Romano Alessandra
Published: November 2019

In the era of novel agents and immunotherapies in solid and liquid tumors, there is an emerging need to understand the cross-talk between the neoplastic cells, the host immune system, and the microenvironment to mitigate proliferation, survival, migration and resistance to drugs. In the microenvironment of hematological tumors there are cells belonging to the normal bone marrow, extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and neoplastic cells themselves. In this context, myeloid suppressor cells are an emerging sub-population of regulatory myeloid cells at different stages of differentiation involved in cancer progression and chronic inflammation. In this review, monocytic myeloid derived suppressor cells and their potential clinical implications are discussed to give a comprehensive vision of their contribution to lymphoproliferative and myeloid disorders.
Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis
Authors: Mihalj Martina , Bujak Maro , Butković Josip , Zubčić Željko , Tolušić Levak Maja , Čes Josip , Kopić Vlatko , Baus Lončar Mirela , Mihalj Hrvoje
Published: November 2019

Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP.
Unravelling the Regions of Mutant F508del-CFTR More Susceptible to the Action of Four Cystic Fibrosis Correctors
Authors: Amico Giulia , Brandas Chiara , Moran Oscar , Baroni Debora
Published: November 2019

Cystic fibrosis (CF) is a genetic disease associated with the defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that causes obstructive disease and chronic bacterial infections in airway epithelia. The most prevalent CF-causing mutation, the deletion of phenylalanine at position 508 (F508del), leads to CFTR misfolding, trafficking defects and premature degradation. A number of correctors that are able to partially rescue F508del-CFTR processing defects have been identified. Clinical trials have demonstrated that, unfortunately, mono-therapy with the best correctors identified to date does not ameliorate lung function or sweat chloride concentration in homozygous F508del patients. Understanding the mechanisms exerted by currently available correctors to increase mutant F508del-CFTR expression is essential for the development of new CF-therapeutics. We investigated the activity of correctors on the mutant F508del and wild type (WT) CFTR to identify the protein domains whose expression is mostly affected by the action of correctors, and we investigated their mechanisms of action. We found that the four correctors under study, lumacaftor (VX809), the quinazoline derivative VX325, the bithiazole compound corr4a, and the new molecule tezacaftor (VX661), do not influence either the total expression or the maturation of the WT-CFTR transiently expressed in human embryonic kidney 293 (HEK293) cells. Contrarily, they significantly enhance the expression and the maturation of the full length F508del molecule. Three out of four correctors, VX809, VX661 and VX325, seem to specifically improve the expression and the maturation of the mutant CFTR N-half (M1N1, residues 1–633). By contrast, the CFTR C-half (M2N2, residues 837–1480) appears to be the region mainly affected by corr4a. VX809 was shown to stabilize both the WT- and F508del-CFTR N-half isoforms, while VX661 and VX325 demonstrated the ability to enhance the stability only of the mutant F508del polypeptide.
Exposure of Larvae of the Solitary Bee Osmia bicornis to the Honey Bee Pathogen Nosema ceranae Affects Life History
Authors: Bramke Kathrin , Müller Uta , McMahon Dino P. , Rolff Jens
Published: November 2019

Wild bees are important pollinators of wild plants and agricultural crops and they are threatened by several environmental stressors including emerging pathogens. Honey bees have been suggested as a potential source of pathogen spillover. One prevalent pathogen that has recently emerged as a honey bee disease is the microsporidian Nosema ceranae. While the impacts of N. ceranae in honey bees are well documented, virtually nothing is known about its effects in solitary wild bees. The solitary mason bee Osmia bicornis is a common pollinator in orchards and amenable to commercial management. Here, we experimentally exposed larvae of O. bicornis to food contaminated with N. ceranae and document spore presence during larval development. We measured mortality, growth parameters, and timing of pupation in a semi-field experiment. Hatched individuals were assessed for physiological state including fat body mass, wing muscle mass, and body size. We recorded higher mortality in the viable-spore-exposed group but could only detect a low number of spores among the individuals of this treatment. Viable-spore-treated individuals with higher head capsule width had a delayed pupation start. No impact on the physiological status could be detected in hatched imagines. Although we did not find overt evidence of O. bicornis infection, our findings indicate that exposure of larvae to viable N. ceranae spores could affect bee development.
Development of a Simple ImageJ-Based Method for Dynamic Blood Flow Tracking in Zebrafish Embryos and Its Application in Drug Toxicity Evaluation
Authors: Santoso Fiorency , Sampurna Bonifasius Putera , Lai Yu-Heng , Liang Sung-Tzu , Hao Erwei , Chen Jung-Ren , Hsiao Chung-Der
Published: November 2019

This study aimed to develop a simple and cost-effective method to measure blood flow in zebrafish by using an image-based approach. Three days post fertilization (dpf) zebrafish embryos were mounted with methylcellulose and subjected to video recording for tracking blood flow under an inverted microscope equipped with a high-speed CCD camera. In addition, Hoffman lens was used to enhance the blood cell contrast. The red blood cell movement was tracked by using the TrackMate plug-in in the ImageJ image processing program. Moreover, Stack Difference and Time Series Analyzer plug-in were used to detect dynamic pixel changes over time to calculate the blood flow rate. In addition to blood flow velocity and heart rate, the effect of drug treatments on other cardiovascular function parameters, such as stroke volume and cardiac output remains to be explored. Therefore, by using this method, the potential side effects on the cardiovascular performance of ethyl 3-aminobenzoate methanesulfonate (MS222) and 3-isobutyl-1-methylxanthine (IBMX) were evaluated. MS222 is a common anesthetic, while IBMX is a naturally occurring methylxanthine. Compared to normal embryos, MS222- and IBMX-treated embryos had a reduced blood flow velocity by approximately 72% and 58%, respectively. This study showed that MS222 significantly decreased the heart rate, whereas IBMX increased the heart rate. Moreover, it also demonstrated that MS222 treatment reduced 50% of the stroke volume and cardiac output. While IBMX decreased the stroke volume only. The results are in line with previous studies that used expensive instruments and complicated software analysis to assess cardiovascular function. In conclusion, a simple and low-cost method can be used to study blood flow in zebrafish embryos for compound screening. Furthermore, it could provide a precise measurement of clinically relevant cardiac functions, specifically heart rate, stroke volume, and cardiac output.
State of Charge Estimation of a Composite Lithium-Based Battery Model Based on an Improved Extended Kalman Filter Algorithm
Authors: Ding Ning , Prasad Krishnamachar , Lie Tek Tjing , Cui Jinhui
Published: November 2019

The battery State of Charge (SoC) estimation is one of the basic and significant functions for Battery Management System (BMS) in Electric Vehicles (EVs). The SoC is the key to interoperability of various modules and cannot be measured directly. An improved Extended Kalman Filter (iEKF) algorithm based on a composite battery model is proposed in this paper. The approach of the iEKF combines the open-circuit voltage (OCV) method, coulomb counting (Ah) method and EKF algorithm. The mathematical model of the iEKF is built and four groups of experiments are conducted based on LiFePO4 battery for offline parameter identification of the model. The iEKF is verified by real battery data. The simulation results with the proposed iEKF algorithm under both static and dynamic operation conditions show a considerable accuracy of SoC estimation.
Factors Associated with Health-Related Quality of Life in Community-Dwelling Older Adults: A Multinomial Logistic Analysis
Authors: Blanco-Reina Encarnación , Valdellós Jenifer , Ocaña-Riola Ricardo , García-Merino María Rosa , Aguilar-Cano Lorena , Ariza-Zafra Gabriel , Bellido-Estévez Inmaculada
Published: November 2019

The main aim of this study was to determine the association of various clinical, functional and pharmacological factors with the physical (PCS) and mental (MCS) summary components of the health-related quality of life (HRQoL) of community-dwelling older adults. Design: Cross-sectional study. Patients and setting: Sample of 573 persons aged over 65 years, recruited at 12 primary healthcare centres in Málaga, Spain. Sociodemographic, clinical, functional, and comprehensive drug therapy data were collected. The main outcome was HRQoL assessed on the basis of the SF-12 questionnaire. A multinomial logistic regression model was constructed to study the relationship between independent variables and the HRQoL variable, divided into intervals. The average self-perceived HRQoL score was 43.2 (± 11.02) for the PCS and 48.5 (± 11.04) for the MCS. The factors associated with a poorer PCS were dependence for the instrumental activities of daily living (IADL), higher body mass index (BMI), number of medications, and presence of osteoarticular pathology. Female gender and the presence of a psychopathological disorder were associated with worse scores for the MCS. The condition that was most strongly associated with a poorer HRQoL (in both components, PCS and MCS) was that of frailty (odds ratio (OR) = 37.42, 95% confidence interval (CI) = 8.96–156.22, and OR = 20.95, 95% CI = 7.55–58.17, respectively). It is important to identify the determinant factors of a diminished HRQoL, especially if they are preventable or modifiable.
High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study
Authors: Garcia Erwin , Osté Maryse C. J. , Bennett Dennis W. , Jeyarajah Elias J. , Shalaurova Irina , Gruppen Eke G. , Hazen Stanley L. , Otvos James D. , Bakker Stephan J. L. , Dullaart Robin P.F. , Connelly Margery A.
Published: November 2019

Background: Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort. Methods: We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Results: Betaine assay results were linear (y = 1.02X − 3.75) over a wide range of concentrations (26.0–1135 µM). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 µM, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5–4.3% and 2.5–5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R2 value of 0.94 (Y = 1.08x – 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 µM (mean of 42.9 ± 12.6 µM). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9–7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44–0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32–0.80, p = 0.003). Conclusions: The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM.
Stress Exposure and the Course of ADHD from Childhood to Young Adulthood: Comorbid Severe Emotion Dysregulation or Mood and Anxiety Problems
Authors: Hartman Catharina A. , Rommelse Nanda , van der Klugt Cees L. , Wanders Rob B.K. , Timmerman Marieke E.
Published: November 2019

Background: Compared to typically developing individuals, individuals with attention-deficit-hyperactivity disorder (ADHD) are on average more often exposed to stressful conditions (e.g., school failure, family conflicts, financial problems). We hypothesized that high exposure to stress relates to a more persistent and complex (i.e., multi-problem) form of ADHD, while low-stress exposure relates to remitting ADHD over the course of adolescence. Method: Longitudinal data (ages 11, 13, 16, and 19) came from the Tracking Adolescents’ Individual Life Survey (TRAILS). We selected children diagnosed with ADHD (n = 244; 167 males; 77 females) from the TRAILS clinical cohort and children who screened positive (n = 365; 250 males; 115 females) and negative (gender-matched: n = 1222; 831 males; 391 females) for ADHD from the TRAILS general population sample cohort (total n = 1587). Multivariate latent class growth analysis was applied to parent- and self-ratings of stress exposure, core ADHD problems (attention problems, hyperactivity/impulsivity), effortful control, emotion dysregulation (irritability, extreme reactivity, frustration), and internalizing problems (depression, anxiety, somatic complaints). Results: Seven distinct developmental courses in stress exposure and psychopathology were discerned, of which four related to ADHD. Two persistent ADHD courses of severely affected adolescents were associated with very high curvilinear stress exposure peaking in mid-adolescence: (1) Severe combined type with ongoing, severe emotional dysregulation, and (2) combined type with a high and increasing internalization of problems and elevated irritability; two partly remitting ADHD courses had low and declining stress exposure: (3) inattentive type, and (4) moderate combined type, both mostly without comorbid problems. Conclusions: High-stress exposure between childhood and young adulthood is strongly intertwined with a persistent course of ADHD and with comorbid problems taking the form of either severe and persistent emotion dysregulation (irritability, extreme reactivity, frustration) or elevated and increasing irritability, anxiety, and depression. Conversely, low and declining stress exposure is associated with remitting ADHD and decreasing internalizing and externalizing problems. Stress exposure is likely to be a facilitating and sustaining factor in these two persistent trajectories of ADHD with comorbid problems into young adulthood. Our findings suggest that a bidirectional, continuing, cycle of stressors leads to enhanced symptoms, in turn leading to more stressors, and so forth. Consideration of stressful conditions should, therefore, be an inherent part of the diagnosis and treatment of ADHD, to potentiate prevention and interruption of adverse trajectories.
Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?
Authors: Pollesello Piero , Ben Gal Tuvia , Bettex Dominique , Cerny Vladimir , Comin-Colet Josep , Eremenko Alexandr A. , Farmakis Dimitrios , Fedele Francesco , Fonseca Cândida , Harjola Veli-Pekka , Herpain Antoine , Heringlake Matthias , Heunks Leo , Husebye Trygve , Ivancan Visnja , Karason Kristjan , Kaul Sundeep , Kubica Jacek , Mebazaa Alexandre , Mølgaard Henning , Parissis John , Parkhomenko Alexander , Põder Pentti , Pölzl Gerhard , Vrtovec Bojan , Yilmaz Mehmet B. , Papp Zoltan
Published: November 2019

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents.
Examination of Manner of Motion Sound Symbolism for English Nonce Verbs
Authors: Eddington David Ellingson , Nuckolls Janis
Published: November 2019

This paper offers cross-experimental verification of a previous study that found that English speakers considered velars, palatals, glides, and high vowels to be sound-symbolic of light and jerky movements. Heavy and smooth movements, by contrast, were associated with affricates, glottals, laterals, and non-high vowels. The present study sought to evaluate these findings through a novel experiment with English speaking subjects, who were asked to choose appropriate sound-symbolically constructed nonce verbs for sentences describing light, heavy, smooth, or jerky manners of motion. Our results support many of Saji et al.’s findings and also offer original insights. We find complex interactions between a sound’s potential for sound-symbolic effects, and its position in initial or second syllables of disyllabic nonce words.
The Effects of Multi-Walled Carbon Nanotubes and Steel Fibers on the AC Impedance and Electromagnetic Shielding Effectiveness of High-Performance, Fiber-Reinforced Cementitious Composites
Authors: Lee Namkon , Kim Sungwook , Park Gijoon
Published: November 2019

This study aimed to investigate the effect of multi-walled carbon nanotubes (MWCNTs) and steel fibers on the AC impedance and electromagnetic shielding effectiveness (SE) of a high-performance, fiber-reinforced cementitious composite (HPFRCC). The electrical conductivity of the 100 MPa HPFRCC with 0.30% MWCNT was 0.093 S/cm and that of the 180 MPa HPFRCC with 0.4% MWCNT and 2.0% steel fiber was 0.10 S/cm. At 2.0% steel fiber and 0.3% MWCNT contents, the electromagnetic SE values of the HPFRCC were 45.8 dB (horizontal) and 42.1 dB (vertical), which are slightly higher than that (37.9 dB (horizontal)) of 2.0% steel fiber content and that (39.2 dB (horizontal)) of 0.3% MWCNT content. The incorporation of steel fibers did not result in any electrical percolation path in the HPFRCC at the micro level; therefore, a high electrical conductivity could not be achieved. At the macro level, the proper dispersion of the steel fibers into the HPFRCC helped reflect and absorb the electromagnetic waves, increasing the electromagnetic SE. The incorporation of steel fibers helped improve the electromagnetic SE regardless of the formation of percolation paths, whereas the incorporation of MWCNTs helped improve the electromagnetic SE only when percolation paths were formed in the cement matrix.
Solid-State Nonlinear Optical Properties of Mononuclear Copper(II) Complexes with Chiral Tridentate and Tetradentate Schiff Base Ligands
Authors: Rigamonti Luca , Forni Alessandra , Cariati Elena , Malavasi Gianluca , Pasini Alessandro
Published: November 2019

Salen-type metal complexes have been actively studied for their nonlinear optical (NLO) properties, and push-pull compounds with charge asymmetry generated by electron releasing and withdrawing groups have shown promising results. As a continuation of our research in this field and aiming at solid-state features, herein we report on the synthesis of mononuclear copper(II) derivatives bearing either tridentate N2O Schiff bases L(a−c)− and pyridine as the forth ancillary ligand, [Cu(La−c)(py)](ClO4) (1a–c), or unsymmetrically-substituted push-pull tetradentate N2O2 Schiff base ligands, [Cu(5-A-5′-D-saldpen/chxn)] (2a–c), both derived from 5-substituted salicylaldehydes (sal) and the diamines (1R,2R)-1,2-diphenylethanediamine (dpen) and (1S,2S)-1,2-diaminocyclohexane (chxn). All compounds were characterized through elemental analysis, infrared and UV/visible spectroscopies, and mass spectrometry in order to guarantee their purity and assess their charge transfer properties. The structures of 1a–c were determined via single-crystal X-ray diffraction studies. The geometries of cations of 1a–c and of molecules 2a–c were optimized through DFT calculations. The solid-state NLO behavior was measured by the Kurtz–Perry powder technique @1.907 µm. All chiral derivatives possess non-zero quadratic electric susceptibility (χ(2)) and an efficiency of about 0.15–0.45 times that of standard urea.
Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells
Authors: Miceli Marco , Cutignano Adele , Conte Mariarosaria , Ummarino Raffaella , Romanelli Alessandra , Ruvo Menotti , Leone Marilisa , Mercurio Flavia Anna , Doti Nunzianna , Manzo Emiliano , Romano Giovanna , Altucci Lucia , Ianora Adrianna
Published: November 2019

Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells.
Comparison between Magnification Techniques and Direct Vision in Thyroid Surgery: A Systematic Review and Meta-Analysis
Authors: Sapalidis Konstantinos , Papanastasiou Anastasios , Fyntanidou Varvara , Aidoni Zoi , Michalopoulos Nikolaos , Katsaounis Athanasios , Amaniti Aikaterini , Zarogoulidis Paul , Koulouris Charilaos , Giannakidis Dimitrios , Ioannidis Aris , Katsios Iason-Nikolaos , Romanidis Konstantinos , Oikonomou Panagoula , Kesisoglou Isaak , Kosmidis Christoforos
Published: November 2019

Background and Objectives: The most common complications after conventional thyroid surgery in adult patients are recurrent laryngeal nerve (RLN) injury and hypocalcemia. Magnification techniques (surgical loupes or surgical microscope) are used for identification of RLN and parathyroid glands to diminish these complications although more evidence is necessary to assess their safety and efficacy in comparison with direct vision. Methods and Materials: Electronic databases (Pubmed, Cochrane Library, Scopus) as well as gray literature sources were searched for randomized controlled trials (RCTs) comparing the frequency of transient/permanent RLN injury and hypocalcemia after thyroid surgery by using magnification techniques and direct vision for identification of RLN and parathyroid glands until October 17, 2019. The main outcomes were transient/permanent RLN injury and hypocalcemia. For all outcomes, 95% confidence intervals (95% CI) were used. Statistical analysis was performed with RevMan 5.3. Results: Systematic review and meta-analysis included 3 RCTs with 437 patients overall. Magnification techniques did not significantly affect the risk of occurrence of transient RLN injury (OR = 0.38, 95% CI (0.11–1.35), I2 = 0%) and transient hypocalcemia (OR = 0.31, 95% CI (0.09–1.09), I2 = 23%) compared with direct vision. Included RCTs demonstrated only two patients with permanent hypocalcemia and another one with permanent RLN injury, who belonged to the direct vision group. Conclusion: The use of magnification techniques for identification of RLN and parathyroid glands seems to be as safe as direct vision. However, they do not decrease the risk of RLN injury and transient hypocalcemia after thyroid surgery compared with direct vision. Finally, further prospective research should be conducted as the sample among the studies was small.
Relationship between Metabolomics Profile of Perilymph in Cochlear-Implanted Patients and Duration of Hearing Loss
Authors: Trinh Thuy-Trân , Blasco Hélène , Emond Patrick , Andres Christian , Lefevre Antoine , Lescanne Emmanuel , Bakhos David
Published: November 2019

Perilymph metabolomic analysis is an emerging innovative strategy to improve our knowledge of physiopathology in sensorineural hearing loss. This study aims to develop a metabolomic profile of human perilymph with which to evaluate the relationship between metabolome and the duration of hearing loss. Inclusion criteria were eligibility for cochlear implantation and easy access to the round window during surgery; patients with residual acoustic hearing in the ear to be implanted were excluded. Human perilymph was sampled from 19 subjects during cochlear implantation surgery. The perilymph analysis was performed by Liquid Chromatography−High-Resolution Mass and data were analyzed by supervised multivariate analysis based on Partial Least-Squares Discriminant Analysis and univariate analysis. Samples were grouped according to their median duration of hearing loss. We included the age of patients as a covariate in our models. Statistical analysis and pathways evaluation were performed using Metaboanalyst. Nineteen samples of human perilymph were analyzed, and a total of 106 different metabolites were identified. Metabolomic profiles were significantly different for subjects with ≤12 or >12 years of hearing loss, highlighting the following discriminant compounds: N-acetylneuraminate, glutaric acid, cystine, 2-methylpropanoate, butanoate and xanthine. As expected, the age of patients was also one of the main discriminant parameters. Metabolic signatures were observed for duration of hearing loss. These findings are promising steps towards illuminating the pathophysiological pathways associated with etiologies of sensorineural hearing loss, and hold open the possibilities of further explorations into the mechanisms of sensorineural hearing loss using metabolomic analysis.
Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis
Authors: Uusitupa Matti , Khan Tauseef A. , Viguiliouk Effie , Kahleova Hana , Rivellese Angela A , Hermansen Kjeld , Pfeiffer Andreas , Thanopoulou Anastasia , Salas-Salvadó Jordi , Schwab Ursula , Sievenpiper John L.
Published: November 2019

Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.