bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex and Polytobacco Use among Spanish and Turkish University Students
Authors: Font-Mayolas Sílvia , Sullman Mark J. M. , Gras Maria-Eugenia
Published: December 2019

Polytobacco use has become increasingly popular among young adults, particularly males, and can be defined as the concurrent use of regular cigarettes and other tobacco products (e.g., e-cigarettes). The present study investigated the use of legal smoking products (cigarettes, waterpipe and electronic cigarettes) among young adults (n = 355) in Spain and Turkey. The survey measured demographics, lifetime and past month tobacco use, waterpipe and e-cigarette use, whether waterpipes and e-cigarettes contained nicotine and reasons for using these substances. The majority of the Turkish (men = 80% and women = 63.9%) and Spanish sample (men = 61.4% and women = 69.3%) were polytobacco users. The most common reason for using e-cigarettes was “to experiment, to see what is like” (Turkish sample: men 66.7% and women 57.1; Spanish sample: men 72.7% and women 93.8%). The most common reason to use regular cigarettes was “to relax and relieve tension” (Turkish sample: men 88.9% and women 77.6%; Spanish sample: men 78.1% and women 76%), while for waterpipe users, the most common reason was “to experiment, to see what it is like” (Turkish sample: men 93.3% and women 80%; Spanish sample: men 78.9% and women 93.8%). The implications for prevention and future research are discussed.
Critical Appraisal of Qualitative Studies of Muslim Females’ Perceptions of Physical Activity Barriers and Facilitators
Authors: Kahan David
Published: December 2019

Muslim women’s perceptions of cultural, religious, and secular determinants of physical activity have been studied for many years, with information typically acquired through focus groups or interviews. Multiple reviews synthesizing the research have been published, however, individual studies have not been scrutinized for their quality/rigor. Therefore, I critically appraised the quality of the body of qualitative research studies that utilized focus groups to identify Muslim women’s perceptions of physical activity barriers and facilitators. I utilized 26 items from the Consolidated Criteria for Reporting Qualitative Research (COREQ) to assess the quality of 56 papers published between 1987 and 2016. Using crosstabulations, I also examined associations between paper quality (low vs. high) and binary categorical variables for impact factor, maximum paper length allowed, publication year, and database the paper was indexed. Overall, papers averaged only 10.5 of 26 COREQ reporting criteria and only two out of 26 items were reported in more than 75% of the papers. Paper quality was not associated with impact factor and length. High quality papers were more likely published more recently (i.e., 2011 or later) and in journals indexed in the PubMed database compared to low quality papers. There is contention among qualitative researchers about standardizing reporting criteria, and while the trend in quality appears to be improving, journal reviewers and editors ought to hold authors to greater accountability in reporting.
Oral Health Knowledge and Related Factors among Pregnant Women Attending to a Primary Care Center in Spain
Authors: Llena Carmen , Nakdali Tasnim , Sanz José Luís , Forner Leopoldo
Published: December 2019

Our aim was to assess the knowledge of pregnant women in terms of oral health and prevention, correlating it with socio-sanitary and educational factors, as well as self-care and oral health state referred. A total of 139 women from a Health Department in Comunidad Valenciana (Valencia, Spain) participated in the study. They underwent an auto-administered survey which included socio-economic and educational factors, self-care in terms of oral hygiene, referred oral health state, and general knowledge on prevention and oral health. Chi-squared test (χ2 test) and ANOVA (p < 0.05) were performed for the analysis. Variables significantly associated with general knowledge were included in a logistic regression analysis. Variables which explained general knowledge in terms of oral health were Spanish nationality (Exp B = 3.59 p = 0.017), secondary/bachelor or equivalent level of education (Exp B = 0.23 p = 0.010), medium or high level of self-care (Exp B = 0.146 p = 0.024 and Exp B = 0.208 p = 0.046, respectively), and medium or high knowledge on prevention (Exp B = 0.092 p = 0.003 and Exp B = 0.280 p = 0.017, respectively). Level of education, nationality, self-care, and knowledge on prevention and oral health were the factors that determined a greater level of general knowledge on oral health from the pregnant women.
Problematic Internet Use and Smoking among Chinese Junior Secondary Students: The Mediating Role of Depressive Symptomatology and Family Support
Authors: Mo Phoenix Kit-han , Li Ji-Bin , Jiang Hui , Lau Joseph T. F.
Published: December 2019

Background: Internet use is significant public health issue and can be a risk factor for other addictive behaviors, such as smoking. The present study examined the association between problematic Internet use (PIU) (i.e., Internet addiction (IA) and social networking addiction (SNA)) and smoking, and the mediating role of depressive symptomatology and family support played in such associations. Methods: A cross-sectional study was conducted among 5182 junior secondary students (grade 7 and 8) recruited from nine schools using stratified sampling. Results: A total of 3.6% of students had smoked in the past month, and 6.4% of students were identified as IA cases. Adjusted for significant background variables, PIU (ORa = 2.07, 95% CI = 1.48, 2.90 for IA, ORa = 1.26, 95% CI = 1.09, 1.47 for SNA), and probable depression (ORa = 1.33, 95% CI = 1.05, 1.69) were significant risk factors, while family support (ORa = 0.85, 95% CI = 0.77, 0.94) was a significant protective factor of smoking. The mediation effects of lower family support and probable depression on the association between score on IA scale and smoking, and the mediation effect of lower family support on the association between score on SNA scale and smoking were significant, while the mediation effect of probable depression on the association between score on SNA scale and smoking was marginally significant. Conclusions: PIU contributed to an increased risk of smoking through depressive symptomatology and decreasing family support among junior school students. Interventions to reduce smoking are warranted; they should seek to reduce problematic Internet use and depressive symptomatology, and promote family support.
A New Analytic Model to Identify Lead Pollution Sources in Soil Based on Lead Fingerprint
Authors: Feng Tao , Wang Cheng-jun , Liu Yong , Chen Meng , Fan Miao-miao , Li Zhi
Published: December 2019

Gobeil’s model is one of the most widely used models to identify lead (Pb) pollution sources in the environment. It is based on a set of equations involving Pb isotope fractions. Although a well-established numerical method, Gobeil’s model is often unable to provide an accurate estimation of each pollution sources’ contribution. This paper comprehensively examines the drawbacks of Gobeil’s model based on a numerical analysis and proposes a revised numerical method that provides a more accurate estimation of Pb pollution sources. Briefly, the mathematical inaccuracy of Gobeil’s model mainly lies in the misinterpretation of “lead fingerprint ratio balance.” To address this problem, the new analytic model relies on the mass balance of total lead in the contaminated sites, and uses a set of linear equations to obtain the contribution of each pollution source based on the lead fingerprint. A subsequent case study from an industrial park in Guanzhong area of Shaanxi Province in China shows that we can calculate the lead contribution rates accurately with the new model.
Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study
Authors: Vernez David , Duperrex Olivier , Herrera Horacio , Perret Vincent , Rossi Isabelle , Regamey Frederic , Guillemin Michel
Published: December 2019

The measurement of an airborne concentration in Amosite fibers above 5035 F/m3 in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52–320 F/m3. The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10−6 to 3 × 10−5 for mesothelioma and 4 × 10−7 to 8 × 10−6 for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers.
Gender Difference in General Self-Efficacy among Young-Old Elderly Aged 60–74 in Rural Shandong China: A Cross-Sectional Survey
Authors: Wang Yali , Xu Lingzhong , Qin Wenzhe , Zhang Jiao , Xia Yu , Jing Xiang , Lu Lu , Jiao An’an , Li Yaozu
Published: December 2019

Objective: This study aims to explore the determinants of general self-efficacy (GSE) among young-old elderly, with focus on examining the gender difference of general self-efficacy. Methods: Data were collected from the 2017 Survey of the Shandong Elderly Family Health Service, which was conducted by Shandong University. T-test was used to examine the gender difference in GSE. Univariate models and adjusted multiple linear regression model were used to explore the determinants of GSE by gender. Results: The females’ GSE score was lower than that of male participants (26.1 ± 8.1 vs. 28.7 ± 7.7), and there was a significant gender difference (t = 10.877, p < 0.001). Multiple linear regression model showed that some factors are common significant determinants of GSE such as age, education level, activity of daily living (ADL), self-rated health, mental health, personality, and whether participants have intimate friends and interpersonal relationships. Hypertension and frequent communication with children were specific determinants of GSE among male young-old. Personal income was a specific determinant of female participants. Conclusion: Some influencing factors of GSE in both genders are identical, the others are different. More attention should be paid for the poor young-old females, young-old males with hypertension, and disabled young-old people.
Acute Limb Ischemia after Intake of the Phenylethylamine Derivate NBOMe
Authors: Wadowski Patricia P. , Giurgea Georgiana-Aura , Schlager Oliver , Luf Anton , Gremmel Thomas , Hobl Eva-Luise , Unterhumer Sylvia , Löffler-Stastka Henriette , Koppensteiner Renate
Published: December 2019

Objective: N-(2-methoxy) benzyl-phenethylamine (NBOMe) derivatives have a high affinity to the serotonin receptor 2A and emerged as new psychedelic agents. We report the case of a 30-year-old man admitted to the hospital because of acute ischemia of the left arm with clinical symptoms of pallor, pulselessness, paresthesia, and a motoric deficit. The patient had a history of schizophrenia and drug abuse and disclosed during the hospital stay the sublingual intake of a substance bought as 25I-NBOMe the night before the ischemic event. Methods: Routine clinical diagnostics including among others color-coded duplex sonography and computed tomography angiography (CTA) were performed. The remainder of the drugs was analyzed using high performance liquid chromatography. Results: Initial color-coded duplex sonography of the upper left limb showed pathological flow profiles of the axillary, brachial, ulnar, and radial artery with a reduced diameter of the ulnar (0.9 mm) and radial (1.1 mm) artery. In consequence, peripheral vasospasm, distal arterial thrombosis, or arterial embolization was anticipated. As therapeutic measures, the patient immediately received intravenous systemic vasodilators (alprostadil) and therapeutic anticoagulation with low molecular weight heparin. Instant symptom improvement was observed within the first day after therapy initiation. The subsequently performed CTA of the heart and left arm showed no signs of thrombotic material. Treatment was continued for five days and the patient was released thereafter having completely normalized perfusion in his left arm. Outpatient treatment was continued with calcium-channel blockers, as the patient had also displayed arterial hypertension. Drug analysis retrieved a composition of the isomers 25I-NBOMe, 25C-NBOMe, and 25H-NBOMe as well as traces of pentylon. Conclusion: NBOMe ingestion implicates the risk of peripheral vasospasms with severe, limb-threatening ischemia.
Farmer Burnout in Canada
Authors: Jones-Bitton Andria , Hagen Briana , Fleming Stephen J. , Hoy Sandra
Published: December 2019

While farmers in several countries worldwide are reported to be at higher risk for poor mental health outcomes like chronic stress, depression, and anxiety, there is a paucity of research on burnout in farmers. This cross-sectional study used an online survey administered between September 2015 and February 2016 to investigate burnout (as measured by the Maslach Burnout Inventory–General Survey (MBI–GS)) amongst farmers in Canada. The specific objectives were to measure the three components of burnout (exhaustion, cynicism, and professional efficacy), and to explore potential associated risk factors, as well as to determine the prevalence of the different burnout profiles (engaged, ineffective, overextended, disengaged, and burnout). MBI–GS results were obtained from 1075 farmers. Approximately 70% of the study sample identified as male and 30% as female, and participants were from a variety of farming commodities. Scores for exhaustion, cynicism, and professional efficacy were all higher than international norms. While 43% of participants were classified as engaged, 44% were classified in the ineffective, overextended, or disengaged profiles (i.e., intermediate profiles on the engagement – burnout continuum), and 12% were classified in the burnout profile. Risk factor results highlighted the positive effects of farmer support from spouse/romantic partner, friends, and industry. Overall, the results from this study demonstrate cause for concern with respect to farmer burnout, suggest potential avenues for intervention, and serve as a call to action to better support farmers in Canada.
Occurrence and Concentration of Chemical Additives in Consumer Products in Korea
Authors: Sardar Syed Wasim , Choi Younghun , Park Naree , Jeon Junho
Published: December 2019

As the variety of chemicals used in consumer products (CPs) has increased, concerns about human health risk have grown accordingly. Even though restrictive guidelines and regulations have taken place to minimize the risks, human exposure to these chemicals and their eco-compatibility has remained a matter of greater scientific concern over the years. A major challenge in understanding the reality of the exposure is the lack of available information on the increasing number of ingredients and additives in the products. Even when ingredients of CPs formulations are identified on the product containers, the concentrations of the chemicals are rarely known to consumers. In the present study, an integrated target/suspect/non-target screening procedure using liquid chromatography-high resolution mass spectrometry (LC-HRMS) with stepwise identification workflow was used for the identification of known, suspect, and unknown chemicals in CPs including cosmetics, personal care products, and washing agents. The target screening was applied to identify and quantify isothiazolinones and phthalates. Among analyzed CPs, isothiazolinones and phthalates were found in 47% and in 24% of the samples, respectively. The highest concentrations were 518 mg/kg for benzisothiazolone, 7.1 mg/kg for methylisothiazolinone, 2.0 mg/kg for diethyl phthalate, and 21 mg/kg for dimethyl phthalate. Suspect and non-target analyses yielded six tentatively identified chemicals across the products including benzophenone, ricinine, iodocarb (IPBC), galaxolidone, triethanolamine, and 2-(2H-Benzotriazol-2-yl)-4, 6-bis (1-methyl-1-phenylethyl) phenol. Our results revealed that selected CPs consistently contain chemicals from multiple classes. Excessive use of these chemicals in daily life can increase the risk for human health and the environment.
Human Health Risk Assessment for Toxic Trace Elements in the Yaro Mine and Reclamation Options
Authors: Kim Min-Suk , Park Mi Jeong , Yang Jeong Hwa , Lee Sang-Hwan
Published: December 2019

The aim of this study was to investigate the environmental impact and human health risks associated with toxic trace element (TTE) exposure in the abandoned Yaro Mine, Korea. Carcinogenic and non-carcinogenic risks were assessed separately for adults and children. Among the various pathways, the rate of TTE intake from the ingestion of groundwater was highest, followed in descending order by crop consumption, soil ingestion, and soil contact. The carcinogenic risk from the ingestion of groundwater was highest, followed by crop consumption and ingestion of contaminated surface soil. The non-carcinogenic risk from the ingestion of groundwater was highest (53.57% of the total non-carcinogenic risk), followed by crop intake (38.53%) and surface soil ingestion (4.80%). The risk assessment revealed that contaminated soil around Yaro mine posed a high risk to the health of inhabitants, mainly via groundwater ingestion and crop consumption. Reclamation measures should include methods of disrupting the high-risk routes between the source and recipient. Stabilization and covering techniques are promising options for reducing the hazard (i.e., exposure to the bioavailable fraction of TTE) and creating a chemical or physicochemical barrier to the potential migration pathways.
Characterizing the Spatial Determinants and Prevention of Malaria in Kenya
Authors: Gopal Sucharita , Ma Yaxiong , Xin Chen , Pitts Joshua , Were Lawrence
Published: December 2019

The United Nations’ Sustainable Development Goal 3 is to ensure health and well-being for all at all ages with a specific target to end malaria by 2030. Aligned with this goal, the primary objective of this study is to determine the effectiveness of utilizing local spatial variations to uncover the statistical relationships between malaria incidence rate and environmental and behavioral factors across the counties of Kenya. Two data sources are used—Kenya Demographic and Health Surveys of 2000, 2005, 2010, and 2015, and the national Malaria Indicator Survey of 2015. The spatial analysis shows clustering of counties with high malaria incidence rate, or hot spots, in the Lake Victoria region and the east coastal area around Mombasa; there are significant clusters of counties with low incidence rate, or cold spot areas in Nairobi. We apply an analysis technique, geographically weighted regression, that helps to better model how environmental and social determinants are related to malaria incidence rate while accounting for the confounding effects of spatial non-stationarity. Some general patterns persist over the four years of observation. We establish that variables including rainfall, proximity to water, vegetation, and population density, show differential impacts on the incidence of malaria in Kenya. The El-Nino–southern oscillation (ENSO) event in 2015 was significant in driving up malaria in the southern region of Lake Victoria compared with prior time-periods. The applied spatial multivariate clustering analysis indicates the significance of social and behavioral survey responses. This study can help build a better spatially explicit predictive model for malaria in Kenya capturing the role and spatial distribution of environmental, social, behavioral, and other characteristics of the households.
Analysis of the Impact of Selected Physical Environmental Factors on the Health of Employees: Creating a Classification Model Using a Decision Tree
Authors: Andrejiová Miriam , Piňosová Miriama , Králiková Ružena , Dolník Bystrík , Liptai Pavol , Dolníková Erika
Published: December 2019

During the process of designing and implementing a working environment, there is a need to guarantee adequate conditions for future workers’ health and well-being. This article addresses the classification of employees characterized by several basic input variables (gender, age, class of work). The investigated variable was the health of employees. This article aims to create a prediction classification model using the classification tree, which can be used to classify new cases into appropriate classes as accurately as possible. Objective measurements of microclimatic parameters were performed by the Testo 435 instrument. The subjective evaluation was performed by a questionnaire survey formed from the training group of 80 respondents and independently verified by the test group of 80 more respondents. The result confusion matrix shows that the number of correctly classified respondents was 69 from a total of 80 respondents. The overall accuracy was A C = 0.863 , which means that the likelihood that respondents are properly classified in the correct health class is 86.3%. Based on the model obtained using the classification tree, we can classify respondents into the relevant class for their state of health. The respondent is classified into the class of work for which particular health and working conditions are most likely.
Equity, Health, and Sustainability with PROVE: The Evaluation of a Portuguese Program for a Short Distance Supply Chain of Fruits and Vegetables
Authors: Craveiro Daniela , Marques Sibila , Marreiros Ana , Bell Ruth , Khan Matluba , Godinho Cristina , Quiroga Sonia , Suárez Cristina
Published: December 2019

PROVE is a Portuguese program that empowers small-scale farmers organized into local networks to directly commercialize baskets of locally produced fruits and vegetables to consumers. This study applied a post-test-only non-equivalent group design to evaluate the resulting influence on the social empowerment of farmers and on consumer diets. The method included conducting a survey of PROVE farmers (n = 36) and a survey of PROVE consumers (n = 294) that were compared against matched samples of Portuguese respondents of international surveys (European Social Survey, n = 36 and the INHERIT Five-Country Survey, n = 571, respectively). PROVE farmers reported higher scores for perceived influence on the work environment than the national sample. PROVE consumers were more likely to eat five or more portions of fruits and vegetables a day in comparison to the matched sample of Portuguese citizens (average odds ratio: 3.05, p < 0.05). Being a PROVE consumer also generated an impact on the likelihood of consuming no more than two portions of red meat a week (average odds ratio: 1.56, p < 0.05). The evaluation study suggests that the promotion of short supply chains of fruits and vegetables can make a positive contribution to a healthier, more sustainable, and fairer future in food consumption.
An Empirical Study on Patients’ Acceptance of Physician-Patient Interaction in Online Health Communities
Authors: Lu Xinyi , Zhang Runtong , Zhu Xiaomin
Published: December 2019

In China, the utilization of medical resources is contentious, and a large of hospitals are seriously congested because of the huge population and uneven distribution of medical resources. Online health communities (OHCs) provide patients with platforms to interact with physicians and to get professional suggestions and emotional support. This study adopted the unified theory of acceptance and use of technology to identify factors influencing patients’ behavioral intention and usage behavior when interacting with physicians in OHCs. An investigation involving 378 valid responses was conducted through several Chinese OHCs to collect data. Confirmatory factor analysis and structural equation modelling were utilized to test hypotheses. Both the reliability and validity of the scales were acceptable. All five hypotheses were supported, and behavioral intention played a significant mediating role between independent variables and dependent variables. This study clarified the mechanism by which performance expectancy, effort expectancy, social influence and attitude toward using technology affect usage behavior through the mediation of behavioral intention in OHCs. These findings suggest that OHCs can change the actions of websites such as adopting some incentives to promote patients’ intention of interaction. Physicians should understand patients’ actual attitudes toward OHCs and try to guide patients in their interactions, improving the quality of physician–patient interaction.
Characterizing Unsafe Sexual Behavior among Factory Workers in the Context of Rapid Industrialization in Northern Vietnam
Authors: Tran Bach Xuan , Vo Tracy , Dang Anh Kim , Nguyen Quang Nhat , Vu Giang Thu , Vu Linh Gia , Do Khanh Nam , Latkin Carl A. , Ho Cyrus S.H. , Ho Roger C.M.
Published: December 2019

Industrial workers or factory workers, especially migrant workers, have been found to be vulnerable populations at risk of sexually transmitted infections (STIs). However, there has been a gap in literature regarding health behaviors of migrant factory workers. We conducted a cross-sectional study among 230 factory workers in Hanoi and Bac Ninh cities in Northern Vietnam from July to September 2018 to identify sexual risk practices and related factors among migrant and nonmigrant factory workers. Information collected regarding sexual behavior included the number of sexual partners in the previous 12 months and whether they used condoms in their last sexual intercourse. Two-thirds of participants reported having no sexual activity in the last 12 months, and there was a low percentage of participants using condoms in their last sexual intercourse. Being female, living with spouses/partners, and being a nonimmigrant had a negative association with the lack of using condoms in the last sexual intercourse with casual partners/sex workers, as opposed to having mobility and self-care problems and identifying as a binge drinker. Therefore, workplace-based prevention programs focusing on providing tailored sexual health education and promoting condom use among industrial workers, especially those who are immigrant or migrant workers, in Vietnam should be emphasized.
Global Mapping of GDP at 1 km2 Using VIIRS Nighttime Satellite Imagery
Authors: Wang Xuantong , Sutton Paul C. , Qi Bingxin
Published: December 2019

Frequent and rapid spatially explicit assessment of socioeconomic development is critical for achieving the Sustainable Development Goals (SDGs) at both national and global levels. Over the past decades, scientists have proposed many methods for estimating human activity on the Earth’s surface at various spatiotemporal scales using Defense Meteorological Satellite Program Operational Line System (DMSP-OLS) nighttime light (NTL) data. However, the DMSP-OLS NTL data and the associated processing methods have limited their reliability and applicability for systematic measuring and mapping of socioeconomic development. This study utilized Visible Infrared Imaging Radiometer Suite (VIIRS) NTL and the Isolation Forest machine learning algorithm for more intelligent data processing to capture human activities. We used machine learning and NTL data to map gross domestic product (GDP) at 1 km2. We then used these data products to derive inequality indexes (e.g., Gini coefficients) at nationally aggregate levels. This flexible approach processes the data in an unsupervised manner at various spatial scales. Our assessments show that this method produces accurate subnational GDP data products for mapping and monitoring human development uniformly across the globe.
Human-Centric Data Science for Urban Studies
Authors: Resch Bernd , Szell Michael
Published: December 2019

Due to the wide-spread use of disruptive digital technologies like mobile phones, cities have transitioned from data-scarce to data-rich environments. As a result, the field of geoinformatics is being reshaped and challenged to develop adequate data-driven methods. At the same time, the term "smart city" is increasingly being applied in urban planning, reflecting the aims of different stakeholders to create value out of the new data sets. However, many smart city research initiatives are promoting techno-positivistic approaches which do not account enough for the citizens’ needs. In this paper, we review the state of quantitative urban studies under this new perspective, and critically discuss the development of smart city programs. We conclude with a call for a new anti-disciplinary, human-centric urban data science, and a well-reflected use of technology and data collection in smart city planning. Finally, we introduce the papers of this special issue which focus on providing a more human-centric view on data-driven urban studies, spanning topics from cycling and wellbeing, to mobility and land use.
Vortioxetine Subchronically Activates Serotonergic Transmission via Desensitization of Serotonin 5-HT1A Receptor with 5-HT3 Receptor Inhibition in Rats
Authors: Okada Motohiro , Okubo Ruri , Fukuyama Kouji
Published: December 2019

Vortioxetine is a novel, multimodal antidepressant with unique targets, including the inhibition of the serotonin transporter (SET), of serotonin 5-HT3 (5-HT3R), and of 5-HT7 (5-HT7R) receptors and partial agonism to serotonin 5-HT1A (5-HT1AR) receptors in humans. Vortioxetine has a lower affinity to 5-HT1AR and 5-HT7R in rats compared with humans, but several behavior studies have demonstrated its powerful antidepressant-like actions. In spite of these efforts, detailed effects of the subchronic administration of vortioxetine on serotonergic transmission remain to be clarified. This study examined the mechanisms underlying the clinical effects of vortioxetine by measuring the releases of 5-HT and GABA in the medial prefrontal cortex (mPFC) of freely moving rats compared with the selective SET inhibitor, escitalopram. Inhibition of 5-HT3R in the mPFC enhanced regional 5-HT release via GABAergic disinhibition. Activation of somatodendritic 5-HT1AR in the dorsal raphe nucleus (DRN) and presynaptic 5-HT1AR in the mPFC inhibited 5-HT release in the mPFC. Escitalopram subchronically activated mesocortical serotonergic transmission via desensitization of 5-HT1AR in the mPFC and DRN and of 5-HT3R in the mPFC; however, vortioxetine also subchronically activated mesocortical serotonergic transmission via desensitization of 5-HT1AR in the mPFC and DRN but not of 5-HT3R in the mPFC. These demonstrations, the desensitization of 5-HT1AR with the inhibition of 5-HT3R (without 5-HT3R desensitization), at least partially, contribute to the multimodal antidepressant action of vortioxetine in rats.
LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical
Authors: Liu Yu-Jiao , Fan Xiao-Yang , Wang An-Dong , Xia Yin-Zheng , Fu Wen-Rong , Liu Jun-Yi , Jiang Feng-Lei , Liu Yi
Published: December 2019

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.
Osteogenic Differentiation of Human Adipose Tissue-Derived MSCs by Non-Toxic Calcium Poly(ethylene phosphate)s
Authors: Nifant’ev Ilya , Bukharova Tatiana , Dyakonov Alexander , Goldshtein Dmitry , Galitsyna Elena , Kosarev Maxim , Shlyakhtin Andrey , Gavrilov Dmitry , Ivchenko Pavel
Published: December 2019

There is a current clinical need for the development of bone void fillers and bioactive bone graft substitutes. The use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation in the event of MSCs osteogenic differentiation is highly promising. Since calcium ions and phosphates promote the osteogenic differentiation of MSCs, the use of the calcium complexes of phosphate-containing polymers is highly prospective in the development of osteogenic scaffolds. Calcium poly(ethylene phosphate)s (PEP-Ca) appear to be potentially suitable candidates primarily because of PEP’s biodegradability. In a series of experiments with human adipose-tissue-derived multipotent mesenchymal stem cells (ADSCs), we demonstrated that PEP-Ca are non-toxic and give rise to osteogenesis gene marker, bone morphogenetic protein 2 (BMP-2) and mineralization of the intercellular matrix. Owing to the synthetic availability of poly(ethylene phosphoric acid) block copolymers, these results hold out the possibility for the development of promising new polymer composites for orthopaedic and maxillofacial surgery.
Systematic Comparison of the Effect of Four Clinical-Grade Platelet Rich Hemoderivatives on Osteoblast Behaviour
Authors: Fernández-Medina Tulio , Vaquette Cedryck , Ivanovski Sašo
Published: December 2019

Hemoderivatives have utilized in an empirical manner, driven by clinical considerations, leading to the development of a plethora of manufacturing protocols. The purpose of this study was to investigate the composition and bioactivity of four common clinical-grade hemoderivates prepared using standardised methods. Four different hemoderivatives were obtained from sheep blood and divided into two groups: A-PRF/i-PRF (fresh) and P-PRP/L-PRP (anticoagulated). Thrombus (CLOT) was used as a control. Thrombocyte quantification, growth factor composition (IGF-I, VEGF, PDGF-BB, BMP-2), cell viability, migration and mineralization assay were evaluated. Platelet recovery was superior for L-PRP followed by P-PRP. A significant cumulative release of IGF-I and PDGF-BB was noted for A-PRF and L-PRP groups at early time points. Similar release profiles of BMP-2 and VEGF were noted in all protocols. Cell viability and migration assay have demonstrated a detrimental effect when the concentration was ≥60%. Moreover, at Day 21, i-PRF have demonstrated superior mineralisation properties when compared to all groups. A negative impact of A-PRF was demonstrated at high concentrations. Despite its low content in growth factors, i-PRF was the best performing blood product for inducing osteoblast mineralisation, and therefore could be the candidate of choice for utilisation in bone tissue engineering applications.
Novel JAG1 Deletion Variant in Patient with Atypical Alagille Syndrome
Authors: Micaglio Emanuele , Andronache Andreea Alina , Carrera Paola , Monasky Michelle M. , Locati Emanuela T. , Pirola Barbara , Presi Silvia , Carminati Mario , Ferrari Maurizio , Giamberti Alessandro , Pappone Carlo
Published: December 2019

Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by various degrees of abnormalities in the liver, heart, eyes, vertebrae, kidneys, face, vasculature, skeleton, and pancreas. This case report describes a newborn child exhibiting a congenital neural tube defect and peculiar craniofacial appearance characterized by a prominent forehead, deep-set eyes, bulbous nasal tip, and subtle upper lip. Just a few hours after birth, congenital heart disease was suspected for cyanosis and confirmed by heart evaluation. In particular, echocardiography indicated pulmonary atresia with ventricular septal defect with severe hypoplasia of the pulmonary branches (1.5 mm), large patent ductus arteriosus and several major aortopulmonary collateral arteries. Due to the association of peculiar craniofacial appearance and congenital heart disease, a form of Alagille syndrome was suspected. In addition, on the fifth day after birth, the patient developed jaundice, had acholic stools, and high levels of conjugated bilirubin and gamma-glutamyltransferase (GGT) were detected in the blood. Genetic testing revealed the novel variant c.802del in a single copy of the JAG1 gene. No variants in the NOTCH2 gene were detected. To the best of our knowledge, this is the first clinical description of a congenital neural tube defect in a molecularly confirmed Alagille patient. This work demonstrates a novel pathogenic heterozygous JAG1 mutation is associated with an atypical form of Alagille syndrome, suggesting an increased risk for neural tube defects compared to other Alagille patients.
Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism
Authors: Muxel Sandra Marcia , Mamani-Huanca Maricruz , Aoki Juliana Ide , Zampieri Ricardo Andrade , Floeter-Winter Lucile Maria , López-Gonzálvez Ángeles , Barbas Coral
Published: December 2019

Background: Leishmaniases are neglected tropical diseases that are caused by Leishmania, being endemic worldwide. L-arginine is an essential amino acid that is required for polyamines production on mammal cells. During Leishmania infection of macrophages, L-arginine is used by host and parasite arginase to produce polyamines, leading to parasite survival; or, by nitric oxide synthase 2 to produce nitric oxide leading to parasite killing. Here, we determined the metabolomic profile of BALB/c macrophages that were infected with L. amazonensis wild type or with L. amazonensis arginase knockout, correlating the regulation of L-arginine metabolism from both host and parasite. Methods: The metabolites of infected macrophages were analyzed by capillary electrophoresis coupled with mass spectrometry (CE-MS). The metabolic fingerprints analysis provided the dual profile from the host and parasite. Results: We observed increased levels of proline, glutamic acid, glutamine, L-arginine, ornithine, and putrescine in infected-L. amazonensis wild type macrophages, which indicated that this infection induces the polyamine production. Despite this, we observed reduced levels of ornithine, proline, and trypanothione in infected-L. amazonensis arginase knockout macrophages, indicating that this infection reduces the polyamine production. Conclusions: The metabolome fingerprint indicated that Leishmania infection alters the L-arginine/polyamines/trypanothione metabolism inside the host cell and the parasite arginase impacts on L-arginine metabolism and polyamine production, defining the infection fate.
Deciphering miRNAs’ Action through miRNA Editing
Authors: Correia de Sousa Marta , Gjorgjieva Monika , Dolicka Dobrochna , Sobolewski Cyril , Foti Michelangelo
Published: December 2019

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.
Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists
Authors: Szabo Adrienn Monika , Viczjan Gabor , Erdei Tamas , Simon Ildiko , Kiss Rita , Szentmiklosi Andras Jozsef , Juhasz Bela , Papp Csaba , Zsuga Judit , Pinter Akos , Szilvassy Zoltan , Gesztelyi Rudolf
Published: December 2019

The receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (cx). The model of RRM describes the co-action of two agonists that consume the same response capacity (due to the use of the same postreceptorial signaling in a biological system). While using RRM, uniquely, an acute increase in the concentration of an agonist (near the receptors) can be quantified (as cx), via evaluating E/c curves that were constructed with the same or another agonist in the same system. As this measurement is sensitive to the implementation of the curve fitting, the goal of the present study was to test RRM by combining different ways and setting options, namely: individual vs. global fitting, ordinary vs. robust fitting, and three weighting options (no weighting vs. weighting by 1/Y2 vs. weighting by 1/SD2). During the testing, RRM was used to estimate the known concentrations of stable synthetic A1 adenosine receptor agonists in isolated, paced guinea pig left atria. The estimates were then compared to the known agonist concentrations (to assess the accuracy of RRM); furthermore, the 95% confidence limits of the best-fit values were also considered (to evaluate the precision of RRM). It was found that, although the global fitting offered the most convenient way to perform RRM, the best estimates were provided by the individual fitting without any weighting, almost irrespective of the fact whether ordinary or robust fitting was chosen.
Loss of p53 Sensitizes Cells to Palmitic Acid-Induced Apoptosis by Reactive Oxygen Species Accumulation
Authors: Yu Guowu , Luo Hongwei , Zhang Na , Wang Yongbin , Li Yangping , Huang Huanhuan , Liu Yinghong , Hu Yufeng , Liu Hanmei , Zhang Junjie , Tang Yi , Huang Yubi
Published: December 2019

Palmitic acid, the most common saturated free fatty acid, can lead to lipotoxicity and apoptosis when overloaded in non-fat cells. Palmitic acid accumulation can induce pancreatic β-cell dysfunction and cardiac myocyte apoptosis. Under various cellular stresses, the activation of p53 signaling can lead to cell cycle arrest, DNA repair, senescence, or apoptosis, depending on the severity/type of stress. Nonetheless, the precise role of p53 in lipotoxicity induced by palmitic acid is not clear. Here, our results show that palmitic acid induces p53 activation in a dose- and time-dependent manner. Furthermore, loss of p53 makes cells sensitive to palmitic acid-induced apoptosis. These results were demonstrated in human colon carcinoma cells (HCT116) and primary mouse embryo fibroblasts (MEF) through analysis of DNA fragmentation, flow cytometry, colony formation, and Western blots. In the HCT116 p53−/− cell line, palmitic acid induced greater reactive oxygen species formation compared to the p53+/+ cell line. The reactive oxygen species (ROS) scavengers N-acetyl cysteine (NAC) and reduced glutathione (GSH) partially attenuated apoptosis in the HCT116 p53−/− cell line but had no obvious effect on the p53+/+ cell line. Furthermore, p53 induced the expression of its downstream target genes, p21 and Sesn2, in response to ROS induced by palmitic acid. Loss of p21 also leads to more palmitic acid-induced cell apoptosis in the HCT116 cell line compared with HCT116 p53+/+ and HCT116 p53−/−. In a mouse model of obesity, glucose tolerance test assays showed higher glucose levels in p53−/− mice that received a high fat diet compared to wild type mice that received the same diet. There were no obvious differences between p53−/− and p53+/+ mice that received a regular diet. We conclude that p53 may provide some protection against palmitic acid- induced apoptosis in cells by targeting its downstream genes in response to this stress.
Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle
Authors: Vágvölgyi Máté , Girst Gábor , Kúsz Norbert , Ötvös Sándor B. , Fülöp Ferenc , Hohmann Judit , Servais Jean-Yves , Seguin-Devaux Carole , Chang Fang-Rong , Chen Michael S. , Chang Li-Kwan , Hunyadi Attila
Published: December 2019

Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein–Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4′-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1′-O-isopropyl ether (6) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety.