bluuebunny/crossref_metadata_2025 huggingface dataset:
New and Emerging Challenges to Heritage and Well-Being: A Critical Review
Authors: Taçon Paul S.C. , Baker Sarah
Published: May 2019

In the past decade, scholarship has documented the ways in which interacting with different forms of heritage impact individual and/or community well-being, as well as the harm to human well-being that occurs when heritage is damaged or destroyed. We bring the results of a review of this literature together, defining both heritage and well-being in relation to each other and exploring the relationship between heritage and well-being. New and emerging threats to heritage and, in turn, well-being are outlined, as well as new ways of preserving heritage for future generations. The future of heritage is discussed along with the importance of the concept of “living heritage”. We conclude that heritage is essential for contemporary and future well-being, and that if we do not better care for heritage then human health will be negatively impacted.
Prevalence and Determinants of Undernutrition in A Sample of Dutch Community-Dwelling Older Adults: Results from Two Online Screening Tools
Authors: Borkent Jos W. , Naumann Elke , Vasse Emmelyne , van der Heijden Ellen , de van der Schueren Marian A. E.
Published: May 2019

To stimulate undernutrition screening among Dutch community-dwelling adults, a website was developed with general information on healthy eating for healthy aging and self-tests. Based on cross-sectional data obtained from the self-tests, we studied nutritional risk factors (early determinants) as well as risk of undernutrition (late symptoms). SCREEN II (n = 2470) was used to asses nutritional risk factors. This tool consists of 16 items regarding nutritional intake, perception of body weight, appetite, oral health and meal preparation. An adjusted SNAQ65+ (n = 687) was used to assess risk of undernutrition. This four-item tool contains questions on weight loss, appetite, walking stairs and body mass index. Differences between age-groups (65–74, 75–84, ≥85) were tested by logistic regression. Overall prevalence of nutritional risk factors was 84.1%, and increased risk of undernutrition was 56.8%. Participants aged ≥85 scored worst on almost all items of the SCREEN II and the SNAQ65+. In conclusion: A large proportion of older adults reported early determinants for increased nutrition risk, while a smaller, yet remarkable proportion scored positive on undernutrition risk. Internet screening may be a useful, contemporary, and easy, accessible way to reach older adults who are at nutritional risk and may thus contribute to early identification and prevention of undernutrition.
Valencia’s Cathedral Church Bell Acoustics Impact on the Hearing Abilities of Bell Ringers
Authors: García Laura , Parra Lorena , Gomis Blanca Pastor , Cavallé Laura , Pérez Guillén Vanesa , Pérez Garrigues Herminio , Lloret Jaime
Published: May 2019

Studies on the effect of occupational noise have been widely performed for occupations such as construction workers, workers of factories or even musicians and workers of nightclubs. However, studies on the acoustics of church bells are very scarce and usually reported in languages other than English. In Spain, although the tradition of bell ringers is progressively getting lost, some bell ringers that continue transmitting the tradition remain. Church bells create sound with a large sound pressure level that can be heard from a great distance. However, despite the characteristics of the sound of church bells, bell ringers do not present symptoms of occupational hearing loss unlike musicians and construction workers. To determine the effects of the sound of the church bells on bell ringers, in this paper, an acoustic study of the church bells and a physiological study of the hearing abilities of bell ringers. Results show sound pressure levels reaching 120 dB inside the bell tower. The resulting hearing loss in bell ringers is small considering the great intensity of the sound produced by the bells. This is likely due to the short amount of time that bell ringers are exposed to the sound even if it reaches high sound pressure levels.
Sexual Activity in Heart Failure Patients: Information Needs and Association with Health-Related Quality of Life
Authors: Baert Anneleen , Pardaens Sofie , De Smedt Delphine , Puddu Paolo Emilio , Ciancarelli Maria Costanza , Dawodu Amos , De Sutter Johan , De Bacquer Dirk , Clays Els
Published: May 2019

(1) Background: the main objective of this study was to investigate information needs concerning sexual activity and experienced sexual problems in heart failure (HF) patients and, in addition, to examine the association between these sexual problems and health-related quality of life (HRQoL); (2) Methods: in this cross-sectional study, three self-administered questionnaires were distributed to 77 stable ambulatory HF patients to acquire data on HRQoL, sexual problems, and need for counselling; (3) Results: More than half (56.7%) of HF patients experienced a marked decrease or total cessation of sexual activity due to their illness. Additionally, more than one-third perceived a marked decrease or total absence of sexual pleasure (42.5%), interest (32.9%), and constant problems or being unable to perform sexual activity (37.3%). Furthermore, 43.1% of patients experienced an important overall need for counselling concerning sexual activity, with information on relationships (69.2%), symptoms (58.5%), and relaxation (49.2%) being the most desired topics. Multiple linear regression analysis revealed that sexual problems were independently associated with HRQoL, with more sexual problems (t = 3.19, p < 0.01) being related to poor HRQoL; (4) Conclusion: by investigating the experienced problems and counselling needs of HF patients, an alignment between current practice and HF patients’ expectations and needs might be obtained.
On the Application of Clustering and Classification Techniques to Analyze Metabolic Syndrome Severity Distribution Area and Critical Factors
Authors: Wang Chien-Chih , Jhu Jin-Jiang
Published: May 2019

In recent years, metabolic syndrome has become one of the leading causes of death in Taiwan. This study proposes a classification and clustering method specific to the administrative regions of New Taipei City to explore the incidence and corresponding risk factors for metabolic syndrome in various geographic areas. We used integrated community health screening data and survey results obtained from people aged ≥40 years in each of the administrative regions of New Taipei City as study samples. Using a combination of Ward’s method, multivariate analysis of variance, and k-means, we identified administrative regions of New Taipei City with metabolic syndrome incidences of a similar nature. Classification and regression tree methods were used to discover the key causes of metabolic syndrome in each region based on lifestyles and dietary habits. The administrative regions were divided into four groups: high-risk, slightly high-risk, normal-risk, and low-risk. The results showed that the severity of metabolic syndrome varies by region and the risk factors for metabolic syndrome vary by region. It has also been found that regions with a higher incidence of metabolic syndrome have relatively fewer medical resources.
A Euclidean Group Assessment on Semi-Supervised Clustering for Healthcare Clinical Implications Based on Real-Life Data
Authors: Sohail Muhammad Noman , Ren Jiadong , Uba Muhammad Musa
Published: May 2019

The grouping of clusters is an important task to perform for the initial stage of clinical implication and diagnosis of a disease. The researchers performed evaluation work on instance distributions and cluster groups for epidemic classification, based on manual data extracted from various repositories, in order to evaluate Euclidean points. This study was carried out on Weka (3.9.2) using 281 real-life health records of diabetes mellitus patients including males and females of ages>20 and <87, who were simultaneously suffering from other chronic disease symptoms, in Nigeria from 2017 to 2018. Updated plugins of K-mean and self-organizing map(SOM) machine learning algorithms were used to cluster the data class of mellitus type for initial clinical implications. The results of the K-mean assessment were built in 0.21 seconds with nine iterations for “type” and eight for “class” attributes. Out of 281 instances, 87 (30.97%) were classified as negative and 194 (69.03%) as positive in the testing on the Euclidean space plot. By assessment for Euclidean points, SOM discovered the search space in a more effective way, but K-mean positioning potencies are impulsive in convergence. This study is important for epidemiological disease diagnosis in countries with a high epidemic risk and low socioeconomic status.
Fetal Cerebral Artery Mitochondrion as Target of Prenatal Alcohol Exposure
Authors: Bukiya Anna N.
Published: May 2019

Prenatal alcohol exposure results in an array of developmental abnormalities known as fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, therapeutic interventions against accidental or intended exposure of developing fetuses to alcohol are limited. This review outlines current knowledge about mitochondria in cerebral blood vessels as a potential target for anti-FASDs intervention. First, it describes the multifaceted role of mitochondria in maintaining the cerebral artery diameter as shown in adult tissue. Second, current literature on alcohol-driven damage of mitochondrial morphology and function in several fetal tissues, including liver, heart, and brain is summarized. The functional consequences of alcohol exposure in these organs include morphological enlargement of mitochondria, increased oxidative stress, and alteration of cellular respiration. These studies point to a tissue-specific effect of alcohol on mitochondrial function and a particular vulnerability of fetal mitochondria to alcohol exposure when compared to adult counterparts. Third, recent work from our group describing persistent changes in fetal baboon cerebral artery proteome following three episodes of prenatal alcohol exposure is reviewed. In conclusion, the consequences of prenatal alcohol exposure on cerebral artery mitochondria constitute an open field of investigation and, eventually, a point of therapeutic intervention against FASDs.
Air Emissions from Natural Gas Facilities in New York State
Authors: Russo Pasquale N. , Carpenter David O.
Published: May 2019

While New York has banned fracking, new and expanded natural gas pipelines are being constructed across the state. Our previous studies have reported that compressor stations are a major source of air pollution at fracking sites. We have used two federal datasets, the U.S. Environmental Protection Agency’s (EPA) National Emissions Inventory and Greenhouse Gas Inventory, to determine what is known concerning emissions from the compressor stations along natural gas pipelines in the state. From a total of 74 compressor stations only 18 report to EPA on emissions. In the seven year period between 2008 and 2014 they released a total of 36.99 million pounds of air pollutants, not including CO2 and methane. This included emissions of 39 chemicals known to be human carcinogens. There was in addition 6.1 billion pounds of greenhouse gases release from ten stations in a single year. These data clearly underestimate the total releases from the state’s natural gas transportation and distribution system. However, they demonstrate significant releases of air pollutants, some of which are known to cause human disease. In addition, they release large amounts of greenhouse gases that contribute to climate change.
Comparison of Older and Newer Generation Active Style Pro Accelerometers in Physical Activity and Sedentary Behavior Surveillance under a Free-Living Environment
Authors: Yano Shohei , Koohsari Mohammad Javad , Shibata Ai , Ishii Kaori , Frehlich Levi , McCormack Gavin R. , Oka Koichiro
Published: May 2019

Background. Comparability of accelerometers in epidemiological studies is important for public health researchers. This study aimed to compare physical activity (light, LPA; moderate, MPA; and moderate-to-vigorous, MVPA) and sedentary behavior (SB) data collected using two Omron triaxial accelerometer generations (Active style Pro, ASP) among a sample of Japanese workers in a free-living environment. Methods. Thirty active and sedentary workers (24–62 years) wore two types of ASP accelerometers, the HJA-350IT (350IT) and the HJA-750C (750C), simultaneously for seven consecutive days to represent a typical week. The accelerometers estimated daily average step counts and time spent per day in LPA, MPA, and MVPA. If a participant had data for ≥4 days (>10 h/day) it was considered valid. The difference and agreement between the two ASPs were analyzed using a paired t-test, intra-class correlation coefficients (ICC), and a Bland–Altman analysis in total and for each type of worker. Results. Among all workers, the 750C measured significantly (p < 0.05) less SB, MPA, MVPA, and more LPA compared with the 350IT. The agreements in ICC were high (ICC ≥ 0.94). Conclusions. Compared with the 350IT, the newer generation 750C ASP accelerometer may not provide equivalent estimates of activity time, regardless of the type of physical activity.
Microbiological Safety of Non-Food Products: What Can We Learn from the RAPEX Database?
Authors: Vincze Szilvia , Al Dahouk Sascha , Dieckmann Ralf
Published: May 2019

For consumer protection across borders, the European Union has established the rapid alert system for dangerous non-food products (RAPEX), with the overarching goal of preventing or limiting the sale and use of non-food products that present a serious risk for the health and safety of consumers. In our study, we comprehensively analyzed RAPEX notifications associated with products posing a microbiological risk from 2005 through 2017. Additional information was retrieved from national laboratory reports. A total of 243 microbiologically harmful consumer products triggered notifications in 23 out of 31 participating countries. About half of the products were reported by Spain, Germany, and Italy. Notifications mainly included contaminated toys, cosmetics, and chemical products. Depending on the notifying country, measures taken to prevent the spread of dangerous products were predominantly ordered either by public authorities or economic operators. The interval between microbiological diagnosis and the date of RAPEX notifications considerably varied between RAPEX member states, ranging between a few days and 82 weeks. The nature and extent of RAPEX usage substantially differed among member states, calling for harmonization and optimization. Slight modifications to RAPEX could help to systematically record microbiological hazards, which may improve the assessment of potential health risks due to contaminated non-food products.
Spatiotemporal Variation of Sediment Export from Multiple Taiwan Watersheds
Authors: Chiang Li-Chi , Wang Yung-Chieh , Liao Ci-Jyun
Published: May 2019

Soil erosion and landslide triggered by heavy rainfall are serious problems that have threatened water resources in Taiwan watersheds. This study investigated the relationship among streamflow, sediment load, sediment concentration and typhoon characteristics (path and rainfall amount) during 2000–2017 for nine gauging stations in five basins (Tamshui River basin, Zhuoshui River basin, Zengwen River basin, Gaoping River basin, and Hualien River basin) representing the diverse geomorphologic conditions in Taiwan. The results showed that streamflow and sediment load were positively correlated, and the correlation was improved when the sediment load data were grouped by sediment concentration. Among these basins, the Zhuoshui River basin has the highest unit-discharge sediment load and unit-area sediment load. The soil in the upstream was more erodible than the downstream soil during the normal discharge conditions, indicating its unique geological characteristics and how typhoons magnified sediment export. The spatiotemporal variation in sediment loads from different watersheds was further categorized by typhoons of different paths. Although typhoon path types matter, the Zhuoshui and Hualien River basin were usually impacted by typhoons of any path type. The results indicated that sediment concentration, the watershed soil characteristics, and typhoons paths were the key factors for sediment loads. This study can be useful for developing strategies of soil and water conservation implementation for sustainable watershed management.
Interactions between 14 Elements in the Human Placenta, Fetal Membrane and Umbilical Cord
Authors: Kot Karolina , Kosik-Bogacka Danuta , Łanocha-Arendarczyk Natalia , Malinowski Witold , Szymański Sławomir , Mularczyk Maciej , Tomska Natalia , Rotter Iwona
Published: May 2019

The aim of the study was to investigate relationships between the concentrations of macroelements (Ca), microelements (Cr, Cu, Fe, Mn, Mo, Ni, Sn, Sr, V, Zn) and heavy metals (Ag, Cd, Pb) in the placenta, fetal membrane and umbilical cord. ‪Furthermore, we examined relationships between the concentrations of these metals in the studied afterbirths and maternal age, gestational age, placenta parameters (breadth, length, weight) and newborn parameters (length, weight and Apgar score). This study confirms previously reported Zn-Cd, Pb-Cd and Ni-Pb interactions in the placenta. New types of interactions in the placenta, fetal membrane and umbilical cord were also noted. Analysis of the correlations between metal elements in the afterbirths (placenta, fetal membrane and umbilical cord) and biological parameters showed the following relationships: maternal age and Mn (in the fetal membrane); gestational age and Cr, Fe, Zn (in the fetal membrane), Ag and Cu (in the umbilical cord); newborn’s length and Sr (in the placenta), Ag (in the umbilical cord); newborn’s weight and Sr (in the placenta), Cu (in the fetal membrane), Ag (in the umbilical cord); Apgar score and Ca, Cr and Ni (in the umbilical cord); placenta’s length and Cr and Sn (in the fetal membrane), Cu (in the umbilical cord); placenta’s width and Mo, Pb (in the placenta) and placenta weight and Sr (in the placenta), Ag, Fe, Mn (in the fetal membrane). The results show the influence of metals on the placenta, mother and newborn parameters, and the same point indicates the essential trace elements during the course of pregnancy.
Effect of Income Heterogeneity on Valuation of Mortality Risk in Taiwan: An Application of Unconditional Quantile Regression Method
Authors: Liou Je-Liang
Published: May 2019

According to theory and existing empirical results, heterogeneity in personal characteristics, with income variation being one of them, affects the marginal willingness to pay (WTP) for reducing fatal risk. In this study, the effect of income heterogeneity on the value of statistical life (VSL) in Taiwan through unconditional quantile regression analysis using the data collected by the “Manpower Utilization Survey” is investigated. The results of this empirical study show that the hedonic wage function that was constructed using empirical data from Taiwan was in line with the general form of non-linear function rather than the semi-log function that has been often used in previous studies, which should have great impact on the estimation of the VSL. The empirical results also show that the estimated VSL of Taiwanese labor varied with the difference in wages, which needs to be taken into account when discussing the public policies using VSL.
Predictors of Seniors’ Interest in Assistive Applications on Smartphones: Evidence from a Population-Based Survey in Slovenia
Authors: Petrovčič Andraž , Peek Sebastiaan , Dolničar Vesna
Published: May 2019

Assistive applications (apps) on smartphones could contribute to a better quality of life for seniors living independently at home. At present, there is a lack of empirical evidence of seniors’ acceptance of such apps. The Cycle of Technology Acquirement by Independent-Living Seniors (C-TAILS) model was recently proposed for studying the interplay between acceptance factors by integrating the personal, social and technological domains of seniors’ daily lives. This study aimed to explore how four groups of factors, clustered in accordance with the C-TAILS model, predict seniors’ interest in assistive apps, on a representative sample of the Slovenian population aged 55 years or older. The 617 respondents, who were contacted though a telephone survey, answered a questionnaire about their interest in three groups of assistive apps and four groups of potentially associated acceptance factors. Three linear regression models were used to analyse the association between the factors and the seniors’ interest in the three types of assistive apps. Smartphone-related dispositional traits were the strongest predictors across all three models. Among mobile phone usage patterns, smartphone use and the breadth of mobile phone features used were significant factors, while the significance of seniors’ personal characteristics and socio-economic conditions varied across the models. Hence, awareness that these factors play different roles in the acceptance of different assistive apps is needed in order to design viable interventions for their acceptance among seniors.
Cell Clearing Systems Bridging Neuro-Immunity and Synaptic Plasticity
Authors: Limanaqi Fiona , Biagioni Francesca , Busceti Carla Letizia , Ryskalin Larisa , Soldani Paola , Frati Alessandro , Fornai Francesco
Published: May 2019

In recent years, functional interconnections emerged between synaptic transmission, inflammatory/immune mediators, and central nervous system (CNS) (patho)-physiology. Such interconnections rose up to a level that involves synaptic plasticity, both concerning its molecular mechanisms and the clinical outcomes related to its behavioral abnormalities. Within this context, synaptic plasticity, apart from being modulated by classic CNS molecules, is strongly affected by the immune system, and vice versa. This is not surprising, given the common molecular pathways that operate at the cross-road between the CNS and immune system. When searching for a common pathway bridging neuro-immune and synaptic dysregulations, the two major cell-clearing cell clearing systems, namely the ubiquitin proteasome system (UPS) and autophagy, take center stage. In fact, just like is happening for the turnover of key proteins involved in neurotransmitter release, antigen processing within both peripheral and CNS-resident antigen presenting cells is carried out by UPS and autophagy. Recent evidence unravelling the functional cross-talk between the cell-clearing pathways challenged the traditional concept of autophagy and UPS as independent systems. In fact, autophagy and UPS are simultaneously affected in a variety of CNS disorders where synaptic and inflammatory/immune alterations concur. In this review, we discuss the role of autophagy and UPS in bridging synaptic plasticity with neuro-immunity, while posing a special emphasis on their interactions, which may be key to defining the role of immunity in synaptic plasticity in health and disease.
Functional Characterization of Colon Cancer-Associated Mutations in ADAM17: Modifications in the Pro-Domain Interfere with Trafficking and Maturation
Authors: Pavlenko Egor , Cabron Anne-Sophie , Arnold Philipp , Dobert Jan Philipp , Rose-John Stefan , Zunke Friederike
Published: May 2019

Colorectal cancer is one of the most commonly diagnosed malignancies in the Western world and is associated with elevated expression and activity of epidermal growth factor receptors (EGF-R). The metalloproteinase ADAM17 is involved in EGF-R activation by processing EGF-R ligands from membrane-bound pro-ligands. Underlining the link between colon cancer and ADAM17, genetic intestinal cancer models in ADAM17-deficient mice show a reduced tumor burden. In this study, we characterize point mutations within the ADAM17 gene found in the tissue of colon cancer patients. In order to shed light on the role of ADAM17 in cancer development, as well as into the mechanisms that regulate maturation and cellular trafficking of ADAM17, we here perform overexpression studies of four ADAM17 variants located in the pro-, membrane-proximal- and cytoplasmic-domain of the ADAM17 protein in ADAM10/17-deficient HEK cells. Interestingly, we found a cancer-associated point mutation within the pro-domain of ADAM17 (R177C) to be most impaired in its proteolytic activity and trafficking to the cell membrane. By comparing this variant to an ADAM17 construct lacking the entire pro-domain, we discovered similar functional limitations and propose a crucial role of the pro-domain for ADAM17 maturation, cellular trafficking and thus proteolytic activity.
Mesenchymal Stem Cell-Conditioned Medium Induces Neutrophil Apoptosis Associated with Inhibition of the NF-κB Pathway in Endotoxin-Induced Acute Lung Injury
Authors: Su Vincent Yi-Fong , Lin Chi-Shiuan , Hung Shih-Chieh , Yang Kuang-Yao
Published: May 2019

The immunomodulatory effects of mesenchymal stem cells (MSCs) are established. However, the effects of MSCs on neutrophil survival in acute lung injury (ALI) remain unclear. The goal of this study was to investigate the effect of an MSC-conditioned medium (MSC-CM) on neutrophil apoptosis in endotoxin-induced ALI. In this study, an MSC-CM was delivered via tail vein injection to wild-type male C57BL/6 mice 4 h after an intratracheal injection of lipopolysaccharide (LPS). Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue were collected to perform histology, immunohistochemistry, apoptosis assay of neutrophil, enzyme-linked immunosorbent assays, and an electrophoretic mobility shift assay. Human neutrophils were also collected from patients with sepsis-induced acute respiratory distress syndrome (ARDS). Human neutrophils were treated in vitro with LPS, with or without subsequent MSC-CM co-treatment, and were then analyzed. Administration of the MSC-CM resulted in a significant attenuation of histopathological changes, the levels of interleukin-6 and macrophage inflammatory protein 2, and neutrophil accumulation in mouse lung tissues of LPS-induced ALI. Additionally, MSC-CM therapy enhanced the apoptosis of BALF neutrophils and reduced the expression of the anti-apoptotic molecules, Bcl-xL and Mcl-1, both in vivo and in vitro experiments. Furthermore, phosphorylated and total levels of nuclear factor (NF)-κB p65 were reduced in lung tissues from LPS + MSC-CM mice. Human MSC-CM also reduced the activity levels of NF-κB and matrix metalloproteinase-9 in the human neutrophils from ARDS patients. Thus, the results of this study suggest that the MSC-CM attenuated LPS-induced ALI by inducing neutrophil apoptosis, associated with inhibition of the NF-κB pathway.
The Effects of Cobalt Protoporphyrin IX and Tricarbonyldichlororuthenium (II) Dimer Treatments and Its Interaction with Nitric Oxide in the Locus Coeruleus of Mice with Peripheral Inflammation
Authors: Moreno Patricia , Cazuza Rafael Alves , Mendes-Gomes Joyce , Díaz Andrés Felipe , Polo Sara , Leánez Sergi , Leite-Panissi Christie Ramos Andrade , Pol Olga
Published: May 2019

Heme oxygenase 1 (HO-1) and carbon monoxide were shown to normalize oxidative stress and inflammatory reactions induced by neuropathic pain in the central nervous system, but their effects in the locus coeruleus (LC) of animals with peripheral inflammation and their interaction with nitric oxide are unknown. In wild-type (WT) and knockout mice for neuronal (NOS1-KO) or inducible (NOS2-KO) nitric oxide synthases with inflammatory pain induced by complete Freund’s adjuvant (CFA), we assessed: (1) antinociceptive actions of cobalt protoporphyrin IX (CoPP), an HO-1 inducer; (2) effects of CoPP and tricarbonyldichlororuthenium(II) dimer (CORM-2), a carbon monoxide-liberating compound, on the expression of HO-1, NOS1, NOS2, CD11b/c, GFAP, and mitogen-activated protein kinases (MAPK) in the LC. CoPP reduced inflammatory pain in different time-dependent manners in WT and KO mice. Peripheral inflammation activated astroglia in the LC of all genotypes and increased the levels of NOS1 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK 1/2) in WT mice. CoPP and CORM-2 enhanced HO-1 and inhibited astroglial activation in all genotypes. Both treatments blocked NOS1 overexpression, and CoPP normalized ERK 1/2 activation. This study reveals an interaction between HO-1 and NOS1/NOS2 during peripheral inflammation and shows that CoPP and CORM-2 improved HO-1 expression and modulated the inflammatory and/or plasticity changes caused by peripheral inflammation in the LC.
Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease
Authors: El Hadi Hamza , Di Vincenzo Angelo , Vettor Roberto , Rossato Marco
Published: May 2019

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
A Novel Immunochromatographic Strip for Antigen Detection of Avian Infectious Bronchitis Virus
Authors: Liu I-Li , Lin Yi-Chun , Lin Yong-Chong , Jian Cai-Zhen , Cheng Ivan-Chen , Chen Hui-Wen
Published: May 2019

Avian infectious bronchitis virus (IBV) causes considerable economic losses in the poultry industry worldwide, including Taiwan. IBV is among the most important pathogens in chickens, and it spreads rapidly among flocks. In addition to dozens of known serotypes, new viral variants have emerged due to the viral evolution and antigenic variation in IBVs. Therefore, the development of a sensitive, specific, and easily performed assay is crucial for the rapid detection and surveillance of IBV infections. A rapid and simple immunochromatographic strip (ICS) was developed in this study by employing monoclonal antibodies against spike and nucleocapsid proteins of IBV as the tracer and the capture antibody. The ICS showed high specificity in detecting IBV antigens, including several IBV genotypes and novel variants, as opposed to three other common avian respiratory viruses. The detection limit of the strip reached 104.4 50% embryo-infective dose. Moreover, in the experimental chicken model, the strip test demonstrated consistency in detecting IBV with RT-PCR gene detection. Taken together, this antigen detection strip has the potential to serve as an on-farm rapid test for IBV; therefore, it may facilitate surveillance and control of the disease.
Cholesterol-Lowering Gene Therapy Prevents Heart Failure with Preserved Ejection Fraction in Obese Type 2 Diabetic Mice
Authors: Aboumsallem Joseph Pierre , Muthuramu Ilayaraja , Mishra Mudit , De Geest Bart
Published: May 2019

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)−/− mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure–volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.
Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib
Authors: Stella Stefania , Zammit Valentina , Vitale Silvia Rita , Pennisi Maria Stella , Massimino Michele , Tirrò Elena , Forte Stefano , Spitaleri Antonio , Antolino Agostino , Siracusa Sergio , Accurso Vincenzo , Mannina Donato , Impera Stefana , Musolino Caterina , Russo Sabina , Malato Alessandra , Mineo Giuseppe , Musso Maurizio , Porretto Ferdinando , Martino Bruno , Di Raimondo Francesco , Manzella Livia , Vigneri Paolo , Stagno Fabio
Published: May 2019

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.
A Comprehensive Bioinformatics Analysis of UBE2C in Cancers
Authors: Dastsooz Hassan , Cereda Matteo , Donna Daniela , Oliviero Salvatore
Published: May 2019

Ubiquitination is one of the main post-translational modification of proteins. It plays key roles in a broad range of cellular functions, including protein degradation, protein interactions, and subcellular location. In the ubiquitination system, different proteins are involved and their dysregulation can lead to various human diseases, including cancers. By using data available from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we here show that the ubiquitin conjugating enzyme, E2C (UBE2C), is overexpressed in all 27 cancers we investigated. UBE2C expression is significantly higher in late-stage tumors, which might indicate its involvement in tumor progression and invasion. This study also revealed that patients with higher UBE2C levels showed a shorter overall survival (OS) time and worse OS prognosis. Moreover, our data show that UBE2C higher-expression leads to worse disease-free survival prognosis (DFS), indicating that UBE2C overexpression correlates with poor clinical outcomes. We also identified genes with positive correlations with UBE2C in several cancers. We found a number of poorly studied genes (family with sequence similarity 72-member D, FAM72D; meiotic nuclear divisions 1, MND1; mitochondrial fission regulator 2, MTFR2; and POC1 centriolar protein A, POC1A) whose expression correlates with UBE2C. These genes might be considered as new targets for cancers therapies since they showed overexpression in several cancers and correlate with worse OS prognosis.
Expression of Ca2+-Binding Buffer Proteins in the Human and Mouse Retinal Neurons
Authors: Kovács-Öller Tamás , Szarka Gergely , Ganczer Alma , Tengölics Ádám , Balogh Boglárka , Völgyi Béla
Published: May 2019

Ca2+-binding buffer proteins (CaBPs) are widely expressed by various neurons throughout the central nervous system (CNS), including the retina. While the expression of CaBPs by photoreceptors, retinal interneurons and the output ganglion cells in the mammalian retina has been extensively studied, a general description is still missing due to the differences between species, developmental expression patterns and study-to-study discrepancies. Furthermore, CaBPs are occasionally located in a compartment-specific manner and two or more CaBPs can be expressed by the same neuron, thereby sharing the labor of Ca2+ buffering in the intracellular milieu. This article reviews this topic by providing a framework on CaBP functional expression by neurons of the mammalian retina with an emphasis on human and mouse retinas and the three most abundant and extensively studied buffer proteins: parvalbumin, calretinin and calbindin.
ClpP Protease, a Promising Antimicrobial Target
Authors: Moreno-Cinos Carlos , Goossens Kenneth , Salado Irene G. , Van Der Veken Pieter , De Winter Hans , Augustyns Koen
Published: May 2019

The caseinolytic protease proteolytic subunit (ClpP) is a serine protease playing an important role in proteostasis of eukaryotic organelles and prokaryotic cells. Alteration of ClpP function has been proved to affect the virulence and infectivity of a number of pathogens. Increased bacterial resistance to antibiotics has become a global problem and new classes of antibiotics with novel mechanisms of action are needed. In this regard, ClpP has emerged as an attractive and potentially viable option to tackle pathogen fitness without suffering cross-resistance to established antibiotic classes and, when not an essential target, without causing an evolutionary selection pressure. This opens a greater window of opportunity for the host immune system to clear the infection by itself or by co-administration with commonly prescribed antibiotics. A comprehensive overview of the function, regulation and structure of ClpP across the different organisms is given. Discussion about mechanism of action of this protease in bacterial pathogenesis and human diseases are outlined, focusing on the compounds developed in order to target the activation or inhibition of ClpP.
The Role of the Stem Cells Therapy in the Peripheral Artery Disease
Authors: Biscetti Federico , Bonadia Nicola , Nardella Elisabetta , Cecchini Andrea Leonardo , Landolfi Raffaele , Flex Andrea
Published: May 2019

Vascular complications of diabetes mellitus are an important issue for all clinicians involved in the management of this complex pathology. Although many therapeutic advances have been reached, peripheral arterial disease is still an unsolved problem that each year compromises the quality of life and life span of affected patients. Oftentimes, patients, after ineffective attempts of revascularization, undergo greater amputations. At the moment, there is no effective and definitive treatment available. In this scenario, the therapeutic use of stem cells could be an interesting option. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the stem cells therapy in this field, from biomarker to possible therapeutic target.
Nitrate Reductase-Mediated Nitric Oxide Regulates the Leaf Shape in Arabidopsis by Mediating the Homeostasis of Reactive Oxygen Species
Authors: Pan Qiao-Na , Geng Chen-Chen , Li Dan-Dan , Xu Shi-Wen , Mao Dan-Dan , Umbreen Saima , Loake Gary John , Cui Bei-Mi
Published: May 2019

As a gaseous biological signaling molecule, nitric oxide (NO) regulates many physiological processes in plants. Over the last decades, this low molecular weight compound has been identified as a key signaling molecule to regulate plant stress responses, and also plays an important role in plant development. However, elucidation of the molecular mechanisms for NO in leaf development has so far been limited due to a lack of mutant resources. Here, we employed the NO-deficient mutant nia1nia2 to examine the role of NO in leaf development. We have found that nia1nia2 mutant plants displayed very different leaf phenotypes as compared to wild type Col-0. Further studies have shown that reactive oxygen species (ROS) levels are higher in nia1nia2 mutant plants. Interestingly, ROS-related enzymes ascorbate peroxidase (APX), catalases (CAT), and peroxidases (POD) have shown decreases in their activities. Our transcriptome data have revealed that the ROS synthesis gene RBOHD was enhanced in nia1nia2 mutants and the photosynthesis-related pathway was impaired, which suggests that NO is required for chloroplast development and leaf development. Together, these results imply that NO plays a significant role in plant leaf development by regulating ROS homeostasis.
High External K+ Concentrations Impair Pi Nutrition, Induce the Phosphate Starvation Response, and Reduce Arsenic Toxicity in Arabidopsis Plants
Authors: Ródenas Reyes , Martínez Vicente , Nieves-Cordones Manuel , Rubio Francisco
Published: May 2019

Potassium (K+) and phosphorous (Pi) are two of the most important nutrients required by plants and there is an interest in studying how they are acquired. Most studies have focused on the characterization of the mechanisms involved in K+ and Pi uptake and their distribution within the plants, as well as the regulatory mechanisms involved. Evidence is emerging which points to interactions in the nutrition of different nutrients and to the existence of crosstalk in the signaling cascades regulating their acquisition. However, the interaction between K+ and Pi has been scarcely studied. Here we show that high concentrations of K+ in the external solution inhibit Pi uptake and impair Pi nutrition in Arabidopsis plants, resulting in the induction of phosphate starvation response (PSR) and the upregulation of genes encoding root phosphate uptake systems. The high K+-induced PSR depends on the PHR1 and PHL1 transcription factors that are key pieces of Pi signaling in Arabidopsis. Importantly, high K+ reduces arsenic accumulation in plants and its toxic effects. The results presented may help to design strategies to reduce Pi deficiency as well as the accumulation of arsenic in crops.
Transcriptomic Pattern of Genes Regulating Protein Response and Status of Mitochondrial Activity Are Related to Oocyte Maturational Competence—A Transcriptomic Study
Authors: Chermuła Błażej , Brązert Maciej , Jeseta Michal , Ożegowska Katarzyna , Kocherova Ievgenia , Jankowski Maurycy , Celichowski Piotr , Sujka-Kordowska Patrycja , Konwerska Aneta , Piotrowska-Kempisty Hanna , Budna-Tukan Joanna , Antosik Paweł , Bukowska Dorota , Machatkova Marie , Brussow Klaus P. , Skowroński Mariusz T. , Pawelczyk Leszek , Bruska Małgorzata , Nowicki Michał , Kempisty Bartosz
Published: May 2019

This paper aims to identify and describe new genetic markers involved in the processes of protein expression and modification reflected in the change of mitochondrial activity before and after in vitro maturation of the oocyte. Porcine oocytes collected from the ovaries of slaughtered landrace gilts were subjected to the process of in vitro maturation. Transcriptomic changes in the expression profile of oocyte genes involved in response to hypoxia, the transmembrane protein receptor serine threonine kinase signaling pathway, the “transforming growth factor β receptor signaling pathway”, “response to protein stimulus”, and “response to organic substance” were investigated using microarrays. The expression values of these genes in oocytes was analyzed before (immature) and after (mature) in vitro maturation, with significant differences found. All the significantly altered genes showed downregulation after the maturation process. The most changed genes from these gene ontologies, FOS, ID2, VEGFA, BTG2, CYR61, ESR1, AR, TACR3, CCND2, CHRDL1, were chosen to be further validated, described and related to the literature. Additionally, the mitochondrial activity of the analyzed oocytes was measured using specific dyes. We found that the mitochondrial activity was higher before the maturation process. The analysis of these results and the available literature provides a novel insight on the processes that occur during in vitro oocyte maturation. While this knowledge may prove to be useful in further research of the procedures commonly associated with in vitro fertilization procedures, it serves mostly as a basic reference for further proteomic, in vivo, and clinical studies that are necessary to translate it into practical applications.
Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity
Authors: Yakoub Kamal M. , Lazzarino Giacomo , Amorini Angela M. , Caruso Giuseppe , Scazzone Concetta , Ciaccio Marcello , Tavazzi Barbara , Lazzarino Giuseppe , Belli Antonio , Di Pietro Valentina
Published: May 2019

Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards N-methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 μM NMDA, followed by incubations (24, 48, and 72 h) without (controls) and with F-1,6-P2 (0.5, 1 or 1.5 mM). At each time, cell necrosis was determined by measuring LDH in the medium. Energy metabolism was evaluated by measuring ATP, GTP, ADP, AMP, and ATP catabolites (nucleosides and oxypurines) in deproteinized OHSC extracts. Gene expressions of phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase were also measured. F-1,6-P2 dose-dependently decreased NMDA excitotoxicity, abolishing cell necrosis at the highest concentration tested (1.5 mM). Additionally, F-1,6-P2 attenuated cell energy imbalance caused by NMDA, ameliorating the mitochondrial phosphorylating capacity (increase in ATP/ADP ratio) Metabolism normalization occurred when using 1.5 mM F-1,6-P2. Remarkable increase in expressions of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase (up to 25 times over the values of controls) was also observed. Since this phenomenon was recorded even in OHSC treated with F-1,6-P2 with no prior challenge with NMDA, it is highly conceivable that F-1,6-P2 can enter into intact cerebral cells producing significant benefits on energy metabolism. These effects are possibly mediated by changes occurring at the gene level, thus opening new perspectives for F-1,6-P2 application as a useful adjuvant to rescue mitochondrial metabolism of cerebral cells under stressing conditions.