bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization and Exergy Analysis of Nuclear Heat Storage and Recovery
Authors: Kluba Anna , Field Robert
Published: November 2019

The APR1400 Nuclear Heat Storage and Recovery (NHS&R) System described here represents the conceptual design and interface of a tertiary cycle with the secondary system of the Korean nuclear reactor plant APR1400. The system is intended to reliably and efficiently store and recover thermal energy from a Nuclear Power Plant (NPP) steam system in order to allow flexible power generation using an economical and scalable design. The research incorporates a comprehensive performance analysis of three interface configurations with comparisons based on the 1st and 2nd Laws of Thermodynamics. The investigated configurations are also ranked based on impact analysis of the NHS&R System on the plant configuration and operation. Input data used in the analysis is based on calibrated thermodynamic models of the system arrangements. Results were used to select the preferred APR1400 NHS&R System design configuration as characterized by: (i) maximum system efficiency, (ii) minimized energy losses, (iii) limited impact on existing plant Systems, Structures, and Components (SSC), and (iv) limited impact on plant operations. Case 3 offers several comparative advantages including: (i) high round trip efficiency, (ii) minimal impact on existing plant and equipment, (iii) high utilization of the heat transport and storage media, and (iv) good system control options.
Technoeconomic Assessment of Hybrid Organosolv–Steam Explosion Pretreatment of Woody Biomass
Authors: Mesfun Sennai , Matsakas Leonidas , Rova Ulrika , Christakopoulos Paul
Published: November 2019

This study investigates technoeconomic performance of standalone biorefinery concepts that utilize hybrid organic solvent and steam explosion pretreatment technique. The assessments were made based on a mathematical process model developed in UniSim Design software using inhouse experimental data. The work was motivated by successful experimental applications of the hybrid pretreatment technique on lignocellulosic feedstocks that demonstrated high fractionation efficiency into a cellulose-rich, a hemicellulose-rich and lignin streams. For the biorefinery concepts studied here, the targeted final products were ethanol, organosolv lignin and hemicellulose syrup. Minimum ethanol selling price (MESP) and Internal rate of return (IRR) were evaluated as economic indicators of the investigated biorefinery concepts. Depending on the configuration, and allocating all costs to ethanol, MESP in the range 0.53–0.95 €/L were required for the biorefinery concepts to break even. Under the assumed ethanol reference price of 0.55 €/L, the corresponding IRR were found to be in the range −1.75–10.7%. Hemicellulose degradation and high steam demand identified as major sources of inefficiencies for the process and economic performance, respectively. Sensitivity of MESP and IRR towards the most influential technical, economic and market parameters performed.
Evaluation Method for Penetration Limit of Renewable Energy Sources in Korean Power System
Authors: Gwon Han , Choi Woo , Kook Kyung
Published: November 2019

As Korea aims to increase the extent to which renewable energy sources (RES) account for up to 20% of the total power generated in the country by 2030, the feasibility of this target is a major concern. This concern largely results from the Korean power system possessing unique characteristics, such as its electrical isolation and high density. To achieve the RES target, the reliable operation of the power system must coexist with an increased share of RES power generation. This study proposes a method to evaluate the penetration limit of RES in the Korean power system considering the existing plans for the long-term electricity supply and demand, as well as its operational requirements. The Korea electric power corporation (KEPCO) planning database of the Korean power system for the next 15 years was employed to determine the penetration limit of RES considering the reliability criteria, including the minimum power generation of conventional sources, primary frequency control requirement, 10-min reserve requirement, and frequency stability.
Time-Lag Effect Between Sap Flow and Environmental Factors of Larix principis-rupprechtii Mayr
Authors: Hong Liu , Guo Jianbin , Liu Zebin , Wang Yanhui , Ma Jing , Wang Xiao , Zhang Ziyou
Published: November 2019

A time lag between sap flux density (Js) and meteorological factors has been widely reported, but the controlling factors of the time lag are poorly understood. To interpret the time lag phenomenon systematically, thermal dissipation probes were placed into each of eight trees to measure the Js of Larix principis-rupprechtii Mayr. in the Liupan Mountains in Northwest China. Meteorological factors, including vapor pressure deficit (VPD), solar radiation (Rs) and air temperature (Ta), were synchronously measured with Js, and the dislocation contrast method was used to analyze the time lag between Js and the meteorological factors. The analysis indicated the following for the whole experimental period. (1) The time lag between Js and VPD (TLV) and the time lag between Js and Rs (TLR) both exhibited different patterns under different weather conditions, and Js could precede Rs on dry days. (2) Both TLV and TLR varied with the day of the year (DOY) throughout the experimental period; namely, both exhibited a decreasing tendency in September. (3) Reference crop evapotranspiration (ETref) had a greater influence on the time lag than the other meteorological factors and directly controlled the length and direction of TLV and TLR; relative extractable water (REW) modified the relationship between ETref and time lag. (4) The regression analysis results showed differences between the time lags and the environmental factors (ETref and REW) within different ranges of REW. Namely, TLR was better determined by ETref and REW when REW < 0.38, while TLV was better correlated with ETref and REW in the absence of soil water limitations (REW > 0.38). This project provided an important opportunity to advance the understanding of the interaction between plant transpiration and meteorological factors in a changing climate.
The Second-Generation Biomethane from Mandarin Orange Peel under Cocultivation with Methanogens and the Armed Clostridium cellulovorans
Authors: Tomita Hisao , Tamaru Yutaka
Published: November 2019

This study demonstrates that the consortium, which consists of the microbial flora of methane production (MFMP) and Clostridium cellulovorans grown with cellulose, can perform the direct conversion of cellulosic biomass to methane. The MFMP was taken from a commercial methane fermentation tank and was extremely complicated. Therefore, C. cellulovorans grown with cellobiose could not perform high degradation ability on cellulosic biomass due to competition by various microorganisms in MFMP. Focusing on the fact that C. cellulovorans was cultivated with cellulose, which is armed with cellulosome, so that it is now armed C. cellulovorans; the direct conversion was carried out by the consortium which consisted of MFMP and the armed C. cellulovorans. As a result, the consortium of C. cellulovorans grown with cellobiose and MFMP (CCeM) could not degrade the purified cellulose and mandarin orange peel. However, MFMP and the armed C. cellulovorans reduced 78.4% of the total sugar of the purified cellulose such as MN301, and produced 6.89 mL of methane simultaneously. Furthermore, the consortium consisted of MFMP and the armed C. cellulovorans degraded mandarin orange peel without any pretreatments and produced methane that was accounting for 66.2% of the total produced gas.
Characterization of Maltase and Sucrase Inhibitory Constituents from Rhodiola crenulata
Authors: Li Wen-Tai , Chuang Yu-Hsuan , Hsieh Jung-Feng
Published: November 2019

The inhibitory properties of epicatechin-(4β,8)-epicatechingallate (B2-3’-O-gallate), epicatechin gallate (ECG), and epicatechin (EC) isolated from Rhodiola crenulata toward maltase and sucrase were investigated. The half-maximal inhibitory concentration (IC50) values for maltase were as follows: B2-3’-O-gallate (1.73 ± 1.37 μM), ECG (3.64 ± 2.99 μM), and EC (6.25 ± 1.84 μM). Inhibition kinetic assays revealed the inhibition constants (Ki) of the mixed-competitive inhibitors of maltase, as follows: B2-3’-O-gallate (1.99 ± 0.02 μM), ECG (3.14 ± 0.04 μM), and EC (7.02 ± 0.26 μM). These compounds also showed a strong inhibitory activity toward sucrase, and the IC50 values of B2-3’-O-gallate, ECG, and EC were 6.91 ± 3.41, 18.27 ± 3.99, and 18.91 ± 3.66 μM, respectively. Inhibition kinetic assays revealed the inhibition constants (Ki) of the mixed-competitive inhibitors of sucrase as follows: B2-3’-O-gallate (6.05 ± 0.04 μM), ECG (8.58 ± 0.08 μM), and EC (13.72 ± 0.15 μM). Overall, these results suggest that B2-3’-O-gallate, ECG, and EC are potent maltase and sucrase inhibitors.
Optimization of a Microplate Assay for Generating Listeria Monocytogenes, E. Coli O157:H7, and Salmonella Biofilms and Enzymatic Recovery for Enumeration
Authors: Aryal Manish , Pranatharthiharan Preetty , Muriana Peter M.
Published: November 2019

Biofilms enable the persistence of pathogens in food processing environments. Sanitizing agents are needed that are effective against pathogens entrapped in biofilms that are more difficult to inactivate than planktonic cells that are displaced and found on equipment surfaces. We examined conditions to develop, analyze, and enumerate the enhanced biofilms of three different foodborne pathogens assisted by fluorescence adherence assay and enzymatic detachment. We compared three different isomeric forms of fluorescent substrates that are readily taken up by bacterial cells based on carboxy-fluorescein diacetate (5-CFDA, 5,6-CFDA, 5,6-CFDA, SE). Biofilm-forming strains of Escherichia coli O157:H7 F4546 and Salmonella Montevideo FSIS 051 were identified using a microplate fluorescence assay defined previously for L. monocytogenes. Adherence levels were determined by differences in relative fluorescence units (RFU) as well as recovered bacterial cells. Multiple hydrolytic enzymes were examined for each representative pathogen for the most suitable enzyme for detachment and enumeration to confirm adherence data obtained by fluorescence assay. Cultures were grown overnight in microplates, incubated, washed and replenished with fresh sterile growth medium; this cycle was repeated for seven consecutive days to enrich for robust biofilms. Treatments were performed in triplicate and compared by one-way analysis of variance (ANOVA) to determine significant differences (p < 0.05).
Storage Stability of Texture and Sensory Properties of Yogurt with the Addition of Polymerized Whey Proteins
Authors: Bierzuńska Paulina , Cais-Sokolińska Dorota , Yiğit Asli
Published: November 2019

Herein, we examined the possibility of producing probiotic yogurt with the addition of polymerized whey protein (PWP). It was determined that the yogurt was stable in terms of syneresis, texture, and sensory features. No spontaneous whey syneresis (SWS) was found in PWP yogurt during 21 days of refrigerated storage at 3 ± 0.5 °C. PWP yogurt had a 5.3% higher water retention capacity (WHC) than yogurt with whey protein concentrate (WPC). Compared with yogurt with unpolymerized protein, PWP yogurt had a higher absolute cohesiveness and viscosity index. The addition of whey protein concentrates to native and polymerized form resulted in longer maintenance of the original yogurt coherence than the control yogurt during storage. PWP yogurt had the same color saturation as the control yogurt. The polymerization of whey proteins resulted in a vanilla pudding aftertaste in yogurt and increased butter flavor 2.5-fold.
Developing and Validating a Method for Separating Flavonoid Isomers in Common Buckwheat Sprouts Using HPLC-PDA
Authors: Jang Davin , Jung Young Sung , Kim Mi-Seon , Oh Seung Eel , Nam Tae Gyu , Kim Dae-Ok
Published: November 2019

Buckwheat sprouts that are synthesized during the germination process are rich in flavonoids, including orientin, vitexin, rutin, and their isomers (isoorientin, isovitexin, and quercetin-3-O-robinobioside, respectively). The purpose of this study was to optimize and validate an analytical method for separating flavonoid isomers in common buckwheat sprout extract (CSE). Factors, such as range, linearity, precision, accuracy, limit of detection, and limit of quantification, were evaluated for each standard using high-performance liquid chromatography (HPLC). On the basis of resolution and symmetry, a column temperature of 40 °C with 0.1% (v/v) acidic water and acetonitrile as mobile phases, at a flow rate of 1 mL min−1 were determined to be the optimal analytical conditions. Calibration curves for orientin, isoorientin, vitexin, isovitexin, and rutin exhibited good linearity with correlation coefficients of 0.9999 over the 6.25–100.00 μg mL−1 range. Recovery values of 96.67–103.60% confirmed that the method was accurate for all flavonoids. The relative standard deviations of intra-day repeatability and inter-day reproducibility confirmed method preciseness, with values of less than 5.21% and 5.40%, respectively. The developed method was used to analyze flavonoids in CSE, with isomers satisfactorily separated and simultaneously quantified. We demonstrated that the developed HPLC method can be used to monitor flavonoids in buckwheat sprouts.
Anthocyanins—Nature’s Bold, Beautiful, and Health-Promoting Colors
Authors: Wallace Taylor C. , Giusti M. Monica
Published: November 2019

Anthocyanins are among the most interesting and vigorously studied plant compounds, representing a large class of over 700 polyphenolic pigments within the flavonoid family that exist ubiquitously in the human diet. They are “nature’s colors,” responsible for providing the beautiful red-orange to blue-violet hues present in many leaves, flowers, vegetables, and fruits, especially berries. The beginning of the 21st century has witnessed a renaissance in research activities on anthocyanins in several areas, mainly related to their potential health-promoting properties and their increased use as alternatives to synthetic food colors. There is increasingly convincing scientific evidence that supports both a preventative and therapeutic role of anthocyanins towards certain chronic disease states. Many anthocyanin-based extracts and juice concentrates from crop and/or food processing waste have become commercially available as colorants and/or value-added food ingredients. There is a large and evolving peer-reviewed literature on how anthocyanin chemistry and concentration may affect their coloring properties in food. Equally as important is the food matrix, which can have large impacts on anthocyanin color expression, stability and degradation, particularly regarding the applications of anthocyanins as food colorants and their health-promoting properties. This Special Edition of Foods, titled “Anthocyanins in Foods,” presents original research that extends our understanding of these exciting and complex compounds.
Creating Age-Friendly Communities: Housing and Technology
Authors: van Hoof Joost , Marston Hannah R. , Brittain Katie R. , Barrie Helen R.
Published: November 2019

Taking an international perspective of healthy ageing, people are living longer and are generally in better health than previous generations [...]
Serological and Molecular Investigation of Coxiella burnetii in Small Ruminants and Ticks in Punjab, Pakistan
Authors: Ullah Qudrat , El-Adawy Hosny , Jamil Tariq , Jamil Huma , Qureshi Zafar Iqbal , Saqib Muhammad , Ullah Shakeeb , Shah Muhammad Kamal , Khan Alam Zeb , Zubair Muhammad , Khan Iahtasham , Mertens-Scholz Katja , Henning Klaus , Neubauer Heinrich
Published: November 2019

Coxiellosis is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii affecting the productive and reproductive capabilities of animals. This study was conducted to gain insight into the seroprevalence of coxiellosis in small ruminants in seven farms of the Punjab, Pakistan. Potential risk factors were assessed. In total, 1000 serum samples (500 from sheep and 500 from goats) and 163 ticks were collected from the ruminants. All these 163 ticks were merged into 55 pools (29 pools for ticks from sheep and 26 pools for ticks from goat). Serum samples were investigated using an indirect ELISA and PCR. Coxiella burnetii DNA was detected in 29 pooled seropositive samples and 11 pooled ticks by real-time qPCR. Serological analysis revealed a prevalence of 15.6% and 15.0% in sheep and goats, respectively. A significant association was found between seropositivity and different variables like district, lactational status, reproductive status, body condition and reproductive disorders. Univariate analysis showed that detection of C. burnetii DNA in tick pools was significantly associated with the presence of ticks on sheep and goats. However, a non-significant association was found for the prevalence of C. burnetii DNA in serum pools. Hence, C. burnetii infection is prevalent in small ruminants and ticks maintained at livestock farms in Punjab, Pakistan.
Fatty Acid Profile of Postmenopausal Women Receiving, and Not Receiving, Hormone Replacement Therapy
Authors: Cybulska Anna Maria , Skonieczna-Żydecka Karolina , Drozd Arleta , Rachubińska Kamila , Pawlik Jolanta , Stachowska Ewa , Jurczak Anna , Grochans Elżbieta
Published: November 2019

Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman’s reproductive lifespan. Menopausal hormonal therapy (MHT) can potentially skew the fatty acid profile increasing the risk for developing metabolic diseases and disorders of skeletal, gastrointestinal, and nervous systems. The aim of this study was to investigate the fatty acid profile of postmenopausal women receiving, and not receiving, hormone replacement therapy. A total of 156 healthy women with a mean age of 60 participated in this cross-sectional study. Gas chromatography with an Agilent Technologies 7890A GC system was used to determine fatty acid content. Statistical analysis was conducted using R software, version 3.4.1. Women receiving MHT had significantly higher (p < 0.05) concentrations of C14:0 and C16:0. MHT was found to be associated with a tendency (p = 0.053) to diminish concentrations of C18:1n-9, C20:4, and all unsaturated fatty acids (p < 0.05). The longer MHT was used, the higher the concentration of C24:1 (p = 0.04) and the lower the concentration of C18:2n-6 (p = 0.03).
Prevalence of Respiratory Health Symptoms among Landfill Waste Recyclers in the City of Johannesburg, South Africa
Authors: Tlotleng Nonhlanhla , Kootbodien Tahira , Wilson Kerry , Made Felix , Mathee Angela , Ntlebi Vusi , Kgalamono Spo , Mokone Moses , Du Preez Karen , Naicker Nisha
Published: November 2019

In developing countries, waste sorting and recycling have become a source of income for poorer communities. However, it can potentially pose significant health risks. This study aimed to determine the prevalence of acute respiratory symptoms and associated risk factors for respiratory health outcomes among waste recyclers. A cross-sectional study was conducted among 361 waste recyclers at two randomly selected landfill sites in Johannesburg. Convenience sampling was used to sample the waste recyclers. The prevalence of respiratory symptoms in the population was 58.5%. A persistent cough was the most common symptom reported (46.8%), followed by breathlessness (19.6%) and rapid breathing (15.8%). Approximately 66.4% of waste recyclers reported exposure to chemicals and 96.6% reported exposure to airborne dust. A multivariable logistic regression analysis showed that exposure to waste containing chemical residues (OR 1.80, 95% CI 1.01–3.22 p = 0.044) increased the odds of respiratory symptoms. There was a significant difference in respiratory symptoms in landfill sites 1 and 2 (OR 2.77, 95% CI 1.03–7.42 p = 0.042). Occupational health and safety awareness is important to minimize hazards faced by informal workers. In addition, providing waste recyclers with the correct protective clothing, such as respiratory masks, and training on basic hygiene practices, could reduce the risks associated with waste sorting.
Aberrant Epigenomic Modulation of Glucocorticoid Receptor Gene (NR3C1) in Early Life Stress and Major Depressive Disorder Correlation: Systematic Review and Quantitative Evidence Synthesis
Authors: Holmes Laurens , Shutman Emily , Chinaka Chinacherem , Deepika Kerti , Pelaez Lavisha , Dabney Kirk W.
Published: November 2019

Early life stress (ELS) induced by psychological trauma, child maltreatment, maternal separation, and domestic violence predisposes to psycho-behavioral pathologies during adulthood, namely major depressive disorder (MDD), anxiety, and bipolar affective disorder. While environmental data are available in illustrating this association, data remain to be established on the epigenomic underpinning of the nexus between ELS and MDD predisposition. Specifically, despite the observed aberrant epigenomic modulation of the NR3C1, a glucocorticoid receptor gene, in early social adversity and social threats in animal and human models, reliable scientific data for intervention mapping in reducing social adversity and improving human health is required. We sought to synthesize the findings of studies evaluating (a) epigenomic modulations, mainly DNA methylation resulting in MDD following ELS, (b) epigenomic modifications associated with ELS, and (c) epigenomic alterations associated with MDD. A systematic review and quantitative evidence synthesis (QES) were utilized with the random effect meta-analytic procedure. The search strategy involved both the PubMed and hand search of relevant references. Of the 1534 studies identified through electronic search, 592 studies were screened, 11 met the eligibility criteria for inclusion in the QES, and 5 examined ELS and MDD; 4 studies assessed epigenomic modulation and ELS, while 2 studies examined epigenomic modulations and MDD. The dense DNA methylation of the 1F exon of the NR3C1, implying the hypermethylated region of the glucocorticoid receptor gene, was observed in the nexus between ELS and MDD, common effect size (CES) = 14.96, 95%CI, 10.06–19.85. With respect to epigenomic modulation associated with child ELS, hypermethylation was observed, CES = 23.2%, 95%CI, 8.00–38.48. In addition, marginal epigenomic alteration was indicated in MDD, where hypermethylation was associated with increased risk of MDD, CES = 2.12%, 95%CI, −0.63–4.86. Substantial evidence supports the implication of NR3C1 and environmental interaction, mainly DNA methylation, in the predisposition to MDD following ELS. This QES further supports aberrant epigenomic modulation identified in ELS as well as major depressive episodes involving dysfunctional glucocorticoid-mediated negative feedback as a result of allostatic overload. These findings recommend prospective investigation of social adversity and its predisposition to the MDD epidemic via aberrant epigenomic modulation. Such data will facilitate early intervention mapping in reducing MDD in the United States population.
The Effect of Brain Breaks on Physical Activity Behaviour among Primary School Children: A Transtheoretical Perspective
Authors: Rizal Hussein , Hajar Mawar Siti , Muhamad Ayu Suzailiana , Kueh Yee Cheng , Kuan Garry
Published: November 2019

Brain Breaks Physical Activity Solutions (BBPAS) is a web-based structured physical activity (PA) video that is specifically designed for school settings and can stimulate a student’s health and learning. The purpose of this study is to measure the effect of BBPAS on the stages of change, decisional balance, processes of change, self-efficacy and leisure-time exercise among Malay ethnic primary school children. A validated Malay version of three of the five constructs was derived with sound validity and was used in the present study. A total of 159 male and 163 female children aged 10 to 11 years old, mean (SD) = 10.53 (0.50), were recruited from two schools in Kelantan, Malaysia. Purposive sampling was used to divide the children into intervention (n = 177) and control (n = 145) groups. Children in the intervention group underwent BBPAS activity for an accumulated 30 min per week, while children in the control group were not involved in the BBPAS intervention. Mixed factorial analysis of variance (ANOVA) was used to examine the effect of BBPAS on the study variables. A mixed ANOVA showed significant changes (time effect) on cognitive process, F(1, 320) = 5.768, p-value = 0.017; behavioural process, F(1, 313) = 5.736, p-value = 0.017; and internal feeling, F(1, 312) = 6.050, p-value = 0.014. There was also a significant difference between groups on cons, F(1, 316) = 7.504, p-value = 0.007. A significant interaction effect was observed for stages of change, F(1, 319) = 7.861, p-value = 0.005; pros, F(1, 316) = 31.311, p-value = 0.001; internal feeling, F(1, 312) = 4.692, p-value = 0.031; and behavioural process, F(1, 313) = 7.312, p-value = 0.007. In conclusion, BBPAS was successful in improving four of the five constructs, and thus, should be recommended to be used in schools throughout Malaysia.
Islamic Finance and Herding Behavior Theory: A Sectoral Analysis for Gulf Islamic Stock Market
Authors: Medhioub Imed , Chaffai Mustapha
Published: November 2019

This study examines herding behavior in four sectors of the Gulf Islamic stock markets. Based on the methodology of Chiang and Zheng (2010), results showed evidence of herding among investors in major sectors for the Gulf Cooperation Council (hereinafter GCC) Islamic stock market during falling periods. In addition, we found that conventional return dispersions have a dominant influence during both falling and rising market periods. We also found evidence of herding around the conventional sectors during down market periods only in banking, hotel and restaurant sectors. There is evidence of herding around the conventional sectors during up market periods for insurance and industrial sectors.
Cell Wall Modifications in Giant Cells Induced by the Plant Parasitic Nematode Meloidogyne incognita in Wild-Type (Col-0) and the fra2 Arabidopsis thaliana Katanin Mutant
Authors: Meidani Christianna , Ntalli Nikoletta G. , Giannoutsou Eleni , Adamakis Ioannis-Dimosthenis S.
Published: November 2019

Meloidogyne incognita is a root knot nematode (RKN) species which is among the most notoriously unmanageable crop pests with a wide host range. It inhabits plants and induces unique feeding site structures within host roots, known as giant cells (GCs). The cell walls of the GCs undergo the process of both thickening and loosening to allow expansion and finally support nutrient uptake by the nematode. In this study, a comparative in situ analysis of cell wall polysaccharides in the GCs of wild-type Col-0 and the microtubule-defective fra2 katanin mutant, both infected with M. incognita has been carried out. The fra2 mutant had an increased infection rate. Moreover, fra2 roots exhibited a differential pectin and hemicellulose distribution when compared to Col-0 probably mirroring the fra2 root developmental defects. Features of fra2 GC walls include the presence of high-esterified pectic homogalacturonan and pectic arabinan, possibly to compensate for the reduced levels of callose, which was omnipresent in GCs of Col-0. Katanin severing of microtubules seems important in plant defense against M. incognita, with the nematode, however, to be nonchalant about this “katanin deficiency” and eventually induce the necessary GC cell wall modifications to establish a feeding site.
Problems Associated with Deprescribing of Proton Pump Inhibitors
Authors: Helgadottir Holmfridur , Bjornsson Einar S.
Published: November 2019

Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.
The Blood–Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders
Authors: Costea Laura , Mészáros Ádám , Bauer Hannelore , Bauer Hans-Christian , Traweger Andreas , Wilhelm Imola , Farkas Attila E. , Krizbai István A.
Published: November 2019

With age, our cognitive skills and abilities decline. Maybe starting as an annoyance, this decline can become a major impediment to normal daily life. Recent research shows that the neurodegenerative disorders responsible for age associated cognitive dysfunction are mechanistically linked to the state of the microvasculature in the brain. When the microvasculature does not function properly, ischemia, hypoxia, oxidative stress and related pathologic processes ensue, further damaging vascular and neural function. One of the most important and specialized functions of the brain microvasculature is the blood–brain barrier (BBB), which controls the movement of molecules between blood circulation and the brain parenchyma. In this review, we are focusing on tight junctions (TJs), the multiprotein complexes that play an important role in establishing and maintaining barrier function. After a short introduction of the cell types that modulate barrier function via intercellular communication, we examine how age, age related pathologies and the aging of the immune system affects TJs. Then, we review how the TJs are affected in age associated neurodegenerative disorders: Alzheimer’s disease and Parkinson’s disease. Lastly, we summarize the TJ aspects of Huntington’s disease and schizophrenia. Barrier dysfunction appears to be a common denominator in neurological disorders, warranting detailed research into the molecular mechanisms behind it. Learning the commonalities and differences in the pathomechanism of the BBB injury in different neurological disorders will predictably lead to development of new therapeutics that improve our life as we age.
Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy
Authors: Wolska Nina , Rozalski Marcin
Published: November 2019

Adenosine receptors are a subfamily of highly-conserved G-protein coupled receptors. They are found in the membranes of various human cells and play many physiological functions. Blood platelets express two (A2A and A2B) of the four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Agonization of these receptors results in an enhanced intracellular cAMP and the inhibition of platelet activation and aggregation. Therefore, adenosine receptors A2A and A2B could be targets for anti-platelet therapy, especially under circumstances when classic therapy based on antagonizing the purinergic receptor P2Y12 is insufficient or problematic. Apart from adenosine, there is a group of synthetic, selective, longer-lasting agonists of A2A and A2B receptors reported in the literature. This group includes agonists with good selectivity for A2A or A2B receptors, as well as non-selective compounds that activate more than one type of adenosine receptor. Chemically, most A2A and A2B adenosine receptor agonists are adenosine analogues, with either adenine or ribose substituted by single or multiple foreign substituents. However, a group of non-adenosine derivative agonists has also been described. This review aims to systematically describe known agonists of A2A and A2B receptors and review the available literature data on their effects on platelet function.
Lack of Delta-Sarcoglycan (Sgcd) Results in Retinal Degeneration
Authors: Perez-Ortiz Andric C. , Peralta-Ildefonso Martha J. , Lira-Romero Esmeralda , Moya-Albor Ernesto , Brieva Jorge , Ramirez-Sanchez Israel , Clapp Carmen , Luna-Angulo Alexandra , Rendon Alvaro , Adan-Castro Elva , Ramírez-Hernández Gabriela , Díaz-Lezama Nundehui , Coral-Vázquez Ramón M. , Estrada-Mena Francisco J.
Published: November 2019

Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for δ-sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd−/−). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd+/+) and Sgcd−/− mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd–protein complex (α-, β-, γ-, and ε-sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd−/− mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the α subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd−/− has a phenotype that is compatible with retinal degeneration.
ZnT8 Haploinsufficiency Impacts MIN6 Cell Zinc Content and β-Cell Phenotype via ZIP-ZnT8 Coregulation
Authors: Lawson Rebecca , Maret Wolfgang , Hogstrand Christer
Published: November 2019

The zinc transporter ZnT8 (SLC30A8) localises to insulin secretory granules of β-cells where it facilitates zinc uptake for insulin crystallisation. ZnT8 abundance has been linked to β-cell survival and functional phenotype. However, the consequences of ZnT8 haploinsufficiency for β-cell zinc trafficking and function remain unclear. Since investigations in human populations have shown SLC30A8 truncating polymorphisms to decrease the risk of developing Type 2 Diabetes, we hypothesised that ZnT8 haploinsufficiency would improve β-cell function and maintain the endocrine phenotype. We used CRISPR/Cas9 technology to generate ZnT8 haploinsufficient mouse MIN6 β-cells and showed that ZnT8 haploinsufficiency is associated with downregulation of mRNAs for Slc39a8 and Slc39a14, which encode for the zinc importers, Znt- and Irt-related proteins 8 (ZIP8) and 14 (ZIP14), and with lowered total cellular zinc content. ZnT8 haploinsufficiency disrupts expression of a distinct array of important β-cell markers, decreases cellular proliferation via mitogen-activated protein (MAP) kinase cascades and downregulates insulin gene expression. Thus, ZnT8 cooperates with zinc importers of the ZIP family to maintain β-cell zinc homeostasis. In contrast to the hypothesis, lowered ZnT8 expression reduces MIN6 cell survival by affecting zinc-dependent transcription factors that control the β-cell phenotype.
Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia
Authors: Ottolenghi Sara , Rubino Federico Maria , Sabbatini Giovanni , Coppola Silvia , Veronese Alice , Chiumello Davide , Paroni Rita
Published: November 2019

Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO2) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO2 = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO2 = 0.80 group with respect to both the FiO2 = 0.40 group and the baseline values (p ≤ 0.05, Student’s t-test). HbSSG in red blood cells was also higher in the FiO2 = 0.80 group at the end of the surgery. NOx was higher in the FiO2 = 0.80 group than the FiO2 = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO2, may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery.
Development of a Multiplex Real-Time PCR Assay for the Newborn Screening of SCID, SMA, and XLA
Authors: Gutierrez-Mateo Cristina , Timonen Anne , Vaahtera Katja , Jaakkola Markku , Hougaard David M , Bybjerg-Grauholm Jonas , Baekvad-Hansen Marie , Adamsen Dea , Filippov Galina , Dallaire Stephanie , Goldfarb David , Schoener Daniel , Wu Rongcong
Published: November 2019

Numerous studies have shown evidence supporting the benefits of universal newborn screening for primary immunodeficiencies (PID) and for Spinal Muscular Atrophy (SMA). We have developed a four-plex, real-time PCR assay to screen for Severe Combined Immune Deficiencies (SCID), X-linked agammaglobulinemia (XLA), and SMA in DNA extracted from a single 3.2 mm punch of a dried blood spot (DBS). A simple, high-throughput, semi-automated DNA extraction method was developed for a Janus liquid handler that can process 384 DBS punches in four 96-well plates in just over one hour with sample tracking capability. The PCR assay identifies the absence of exon 7 in the SMN1 gene, while simultaneously evaluating the copy number of T-cell receptor excision circles (TREC) and Kappa-deleting recombination excision circles (KREC) molecules. Additionally, the amplification of a reference gene, RPP30, was included in the assay as a quality/quantity indicator of DNA isolated from the DBS. The assay performance was demonstrated on over 3000 DNA samples isolated from punches of putative normal newborn DBS. The reliability and analytical accuracy were further evaluated using DBS controls, and contrived and confirmed positive samples. The results from this study demonstrate the potential of future molecular DBS assays, and highlight how a multiplex assay could benefit newborn screening programs.
Metamodel-Assisted Multidisciplinary Design Optimization of a Radial Compressor
Authors: Aissa Mohamed H. , Verstraete Tom
Published: November 2019

Kriging is increasingly used in metamodel-assisted design optimization. For expensive simulations; however, one can afford only a few samples to build the Kriging model, which consequently lacks prediction accuracy. We propose a bounded Kriging able to handle optimization problems with a small initial database. During the optimization, the proposed Kriging suggests designs close to database samples and finds optimal designs while staying in a feasible region (with respect to mesh and CFD convergence). The bounded Kriging is applied along with the ordinary Kriging to a multidisciplinary design optimization of a radial compressor. The shape of the compressor blades is optimized by considering the aero performance at different operating points and the mechanical stresses. The objective of the optimization is to maximize the efficiency at two operating points, while constraints are imposed on the maximum stress level in the material, the choke mass flow, the pressure ratio and the momentum of inertia of the impeller. While ordinary Kriging stopped prematurely because of many failing design evaluations, the bounded Kriging satisfied all constraints and reached an improvement of 2.59% in efficiency over the baseline design that does not comply with any constraints. The bounded Kriging covers a special need for robust methods in optimization able to deal with challenging geometries and a small database, which is the case for most industrial design optimizations.
Krox20 Regulates Endothelial Nitric Oxide Signaling in Aortic Valve Development and Disease
Authors: Odelin Gaëlle , Faure Emilie , Maurel-Zaffran Corinne , Zaffran Stéphane
Published: November 2019

Among the aortic valve diseases, the bicuspid aortic valve (BAV) occurs when the aortic valve has two leaflets (cusps), rather than three, and represents the most common form of congenital cardiac malformation, affecting 1–2% of the population. Despite recent advances, the etiology of BAV is poorly understood. We have recently shown that Krox20 is expressed in endothelial and cardiac neural crest derivatives that normally contribute to aortic valve development and that lack of Krox20 in these cells leads to aortic valve defects including partially penetrant BAV formation. Dysregulated expression of endothelial nitric oxide synthase (Nos3) is associated with BAV. To investigate the relationship between Krox20 and Nos3 during aortic valve development, we performed inter-genetic cross. While single heterozygous mice had normal valve formation, the compound Krox20+/−;Nos3+/− mice had BAV malformations displaying an in vivo genetic interaction between these genes for normal valve morphogenesis. Moreover, in vivo and in vitro experiments demonstrate that Krox20 directly binds to Nos3 proximal promoter to activate its expression. Our data suggests that Krox20 is a regulator of nitric oxide in endothelial-derived cells in the development of the aortic valve and concludes on the interaction of Krox20 and Nos3 in BAV formation.
Progressive Pulmonary Artery Dilatation is Associated with Type B Aortic Dissection in Patients with Marfan Syndrome
Authors: Brouwer Christel , Bulut Haldun , van Gemert Willemijn , Staal Alexander HJ , Cortenbach Kim , Snoeren Miranda , Nijveldt Robin , Duijnhouwer Anthonie , Loeys Bart L , van Royen Niels , Timmermans Janneke , van Kimmenade Roland RJ
Published: November 2019

Objective: Marfan syndrome (MFS) is a connective tissue disorder associated with severe cardiovascular morbidity and mortality. It is unknown if aorta complications in MFS are associated with progressive pulmonary artery (PA) dilatation. Methods: We measured the PA diameter on routine magnetic resonance imaging in a population of MFS patients seen in our specialised centre with follow up of diameters as well as the outcome. Results: PA dilatation was defined as an increase in diameter of 2 mm or more, and 71 patients (44%) of our total cohort (n = 162) met this criterion; mean follow up between two scans was 8.6 years (standard deviation (SD) ± 2.7 years). Furthermore, 28 patients suffered from dissections, of which 14 had a type A dissection, 10 had a type B dissection, and 4 patients suffered from both. Of those who suffered from dissection, 64% (18 out of 28) had a dilatation of the PA, versus 39% (53 out of 134) in the patient group without a dissection (p < 0.05). There was a significant association between type B dissection and descending aorta diameter (OR 1.14; 95% CI 1.05–1.24 p < 0.01) and PA dilatation (OR 1.69; 95% CI 1.03–2.77 p = 0.04). In the multivariable analysis the final model for type B dissection, only systolic blood pressure (OR 1.06; 95% CI 1.01–1.11 p = 0.02) and PA dilatation were statistically significant (OR 1.85; 95% CI 1.10–3.12 p = 0.02) while descending aorta diameter was not. Conclusions: We report an association between progressive PA dilatation and type B dissection. Our findings encourage a renewed interest in PA dimensions in MFS.
Biofilm Formation by Staphylococcus aureus Clinical Isolates is Differentially Affected by Glucose and Sodium Chloride Supplemented Culture Media
Authors: Lade Harshad , Park Joon Hyun , Chung Sung Hee , Kim In Hee , Kim Jung-Min , Joo Hwang-Soo , Kim Jae-Seok
Published: November 2019

Staphylococcus aureus (S. aureus) causes persistent biofilm-related infections. Biofilm formation by S. aureus is affected by the culture conditions and is associated with certain genotypic characteristics. Here, we show that glucose and sodium chloride (NaCl) supplementation of culture media, a common practice in studies of biofilms in vitro, influences both biofilm formation by 40 S. aureus clinical isolates (methicillin-resistant and methicillin-sensitive S. aureus) and causes variations in biofilm quantification. Methicillin-resistant strains formed more robust biofilms than methicillin-sensitive strains in tryptic soy broth (TSB). However, glucose supplementation in TSB greatly promoted and stabilized biofilm formation of all strains, while additional NaCl was less efficient in this respect and resulted in significant variation in biofilm measurements. In addition, we observed that the ST239-SCCmec (Staphylococcal Cassette Chromosome mec) type III lineage formed strong biofilms in TSB supplemented with glucose and NaCl. Links between biofilm formation and accessory gene regulator (agr) status, as assessed by δ-toxin production, and with mannitol fermentation were not found. Our results show that TSB supplemented with 1.0% glucose supports robust biofilm production and reproducible quantification of S. aureus biofilm formation in vitro, whereas additional NaCl results in major variations in measurements of biofilm formation.