bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Intelligence and Psychological Distress: Subjective and Psychological Well-Being as Mediators
Authors: Azañedo Carolina M. , Sastre Santiago , Artola Teresa , Alvarado Jesús M. , Jiménez-Blanco Amelia
Published: October 2020

The strength named “social intelligence” in the Values in Action (VIA) Classification of Character Strengths and Virtues represents emotional, personal, and social intelligences, which are considered “hot intelligences”. This work contributed to the study of the mechanisms of influence of social intelligence on mental health. A multiple mediation model was proposed to quantify the direct effect of social intelligence on psychopathological symptoms, as well as its indirect effect through its impact on components of subjective and psychological well-being. This study involved 1407 university students who completed the Values in Action Inventory of Strengths (VIA-IS), the Satisfaction with Life Scale (SWLS), the Positive and Negative Affect Schedule (PANAS), the Psychological Well-Being Scales (PWBS), and the Symptom Checklist-90-Revised (SCL-90-R). Social intelligence was found to be significantly associated with life satisfaction (a = 0.33, p < 0.001), positive affect (a = 0.42, p < 0.001), and negative affect (a = −0.21, p < 0.001), transmitting significant indirect effects on psychopathological symptomatology through these components of subjective well-being. Likewise, social intelligence was positively and significantly related to psychological well-being (a-paths ranged from 0.31 to 0.43, p < 0.001), exerting significant and negative indirect effects on psychological distress through the dimension of positive relations with other people. These results could be useful in order to expand the explanatory models of the influence of social intelligence on mental health and to design interventions based on this strength for the promotion of well-being and the reduction in psychological distress.
Gender Effect on Political Leaders’ Nonverbal Communicative Structure during the COVID-19 Crisis
Authors: Grebelsky-Lichtman Tsfira , Katz Roy
Published: October 2020

During the COVID-19 pandemic, there has been intense interest in political leaders’ nonverbal communicative structures (NCS) during televised appearances. This study analyzes the effect of gender on leaders’ NCS and presents theoretical and analytical frameworks of gendered NCS. We analyzed 20 televised appearances by 10 heads of state (five males and five females) from democratic Western countries during the COVID-19 pandemic. The findings revealed that gender had a significant effect on leaders’ NCS, indicating that leaders presented NCS that corresponded to their gender. Male leaders’ masculine NCS included competition, warning, threatening, and scaring behavior, broad proxemics, tension leakage, and illustrative gestures, while female leaders presented feminine NCS of cooperativeness, emotional communication, empathy, optimism, eye contact, and flexible expressions. Furthermore, the effect of gender on leaders’ NCS had an interaction effect with the situation of the pandemic, indicating that countries with a female leader had fewer diseased and severe cases and more calmness and healing NCS. The conclusions present theoretical and analytical frameworks that explain the central effect of gender on contemporary leaders’ NCS. This study develops advanced distinctive profiles for male versus female leaders’ NCS of emotions, cognition, and behavior during a crisis.
Fundamental Concepts of Human Thermoregulation and Adaptation to Heat: A Review in the Context of Global Warming
Authors: Lim Chin Leong
Published: October 2020

The international community has recognized global warming as an impending catastrophe that poses significant threat to life on earth. In response, the signatories of the Paris Agreement (2015) have committed to limit the increase in global mean temperature to <1.5 °C from pre-industry period, which is defined as 1850–1890. Considering that the protection of human life is a central focus in the Paris Agreement, the naturally endowed properties of the human body to protect itself from environmental extremes should form the core of an integrated and multifaceted solution against global warming. Scholars believe that heat and thermoregulation played important roles in the evolution of life and continue to be a central mechanism that allows humans to explore, labor and live in extreme conditions. However, the international effort against global warming has focused primarily on protecting the environment and on the reduction of greenhouse gases by changing human behavior, industrial practices and government policies, with limited consideration given to the nature and design of the human thermoregulatory system. Global warming is projected to challenge the limits of human thermoregulation, which can be enhanced by complementing innate human thermo-plasticity with the appropriate behavioral changes and technological innovations. Therefore, the primary aim of this review is to discuss the fundamental concepts and physiology of human thermoregulation as the underlying bases for human adaptation to global warming. Potential strategies to extend human tolerance against environmental heat through behavioral adaptations and technological innovations will also be discussed. An important behavioral adaptation postulated by this review is that sleep/wake cycles would gravitate towards a sub-nocturnal pattern, especially for outdoor activities, to avoid the heat in the day. Technologically, the current concept of air conditioning the space in the room would likely steer towards the concept of targeted body surface cooling. The current review was conducted using materials that were derived from PubMed search engine and the personal library of the author. The PubMed search was conducted using combinations of keywords that are related to the theme and topics in the respective sections of the review. The final set of articles selected were considered “state of the art,” based on their contributions to the strength of scientific evidence and novelty in the domain knowledge on human thermoregulation and global warming.
Impact of Physical Activity on Challenging Obesity in Pakistan: A Knowledge, Attitude, and Practice (KAP) Study
Authors: Laar Rizwan Ahmed , Shi Shusheng , Ashraf Muhammad Azeem , Khan Muhammad Naeem , Bibi Jannat , Liu Yibing
Published: October 2020

Physical activity (PA) refers to any action produced by skeletal muscle that consumes energy. According to the World Health Organization (WHO), PA is the primary element that can improve health at the community level. Obviously, PA plays an important role in the social, physical, and mental development of men and women, as well as in balancing weight. However, the large-scale negative impacts of physical inactivity on health-related issues are also recognized globally, such as obesity, which is the source of many non-communication diseases (NCDs). In Pakistan alone, 46% of deaths occur due to NCD. The majority of NCD deaths are linked to obesity, and Pakistan is the ninth most obese country in the world. Research on obesity caused by sedentary work in Pakistan is lacking, especially among university employees. To fill this gap, the current study mainly focuses on the rising non-communicable disease (NCD) rates among university employees in Pakistan due to a lack of exercise (obesity, in this case), with the help of a self-designed knowledge, attitude, and practice (KAP) questionnaire. Five universities in the Sindh province of Pakistan were surveyed (n = 276), following the concept of Yin–Yang as a theoretical lens. The results of the current study show that the knowledge, behaviors, and attitudes of university employees have a great influence on their body mass index (BMI). The study shows that Pakistani residents’ (especially teaching staff) perceptions and attitudes towards obesity and PA have been instructive, but their practices need to be improved.
Stunting Rates in a Food-Rich Country: The Argentine Pampas from the 1850s to the 1950s
Authors: Salvatore Ricardo D.
Published: October 2020

Little is known about the effects of malnutrition rates in the long-run. Applying the methodology recommended by the World Health Organization, this study estimates stunting rates for Argentine adult males from the 1850s to the 1950s. We use five large samples of army recruits, prison inmates, militiamen, and electoral records totaling 84,500 cases. These samples provide information about height in Buenos Aires province and the Pampa region, the most fertile, food-producing area of the country. As the study shows, estimated stunting rates remained stable from the 1850s to the 1880s and then declined persistently until the 1950s. The total decline was substantial: if fell from 15.3% in the 1870s to 5.6% in the 1940s, then stagnated. In this 95-year period, stunting rates went from “medium” to “low” levels in the WHO classification of malnutrition intensity. At the end of our study period (the 1950s) the Pampa’s malnutrition rate was only 3.5 to 4 percentage points above contemporary estimates for well-developed economies in Europe and North America. A significant expansion in the region’s production of grains and beef (food availability), combined with a sustained decline in infant mortality (increased health) were probably the two main underlying factors of this long-tern reduction in malnutrition. Yet, this association remains to be determined.
Experiences of Women with Male Factor Infertility under In Vitro Fertilization
Authors: Kim Miok , Yi Su Jeong , Hong Ju Eun
Published: October 2020

Purpose: This study attempts to explore the experiences of infertility among women with male factor infertility. Methods: From April to July 2018, nine women with experience of male factor infertility and assistant reproductive technology were interviewed. The transcribed data were qualitatively analyzed to identify major themes and sub-themes representing participants’ experiences with male factor infertility. Results: The analysis indicated that the women’s infertility experiences were structured into five theme clusters: “Difficult to accept the situation”, “Confused inside”, “Destroyed relationships due to blaming and anger”, “Desire social support”, and “Embracing hurt feelings and regaining strength”. Conclusions: Intervention programs are needed to closely investigate the psychological status of women with male factor infertility and help with their physical and psychological well-being. Efforts to address infertility through effective governmental support for infertility, a strategy for promoting the social recognition of infertility, and the health professional’s persistent interest and collaboration, are discussed.
The Dually Negative Effect of Industrial Polluting Enterprises on China’s Air Pollution: A Provincial Panel Data Analysis Based on Environmental Regulation Theory
Authors: Lyu Shoujun , Shen Xingchi , Bi Yujie
Published: October 2020

Although the Chinese government has promulgated a series of policies to mitigate air pollution, the air quality in a number of Chinese cities still has the potential to be improved. As the major source of air pollution, enterprises in the industrial and energy sectors are the most difficult to regulate in terms of polluting emissions. This paper aims to investigate what factors influence the intensity of environmental regulations on polluting enterprises based on environmental regulation theory and an empirical test. Firstly, this article builds a theoretic model of optimal regulation supply for local governments in order to examine the relationship between factors influencing the intensity of environmental regulation. Secondly, we use provincial panel data from 2008 to 2015 to test the theoretical hypothesis and use the generalized method of moments (GMM), the two-stage least squares (2SLS) method to address the endogeneity issue. The main finding of the study is that, in regions with a high concentration of polluting enterprises, not only is there more air pollution than in other regions, but the local governments might show partiality towards the polluting enterprises, which could impede the implementation of environmental regulation.
Emotion Regulation Strategies, Workload Conditions, and Burnout in Healthcare Residents
Authors: Martín-Brufau Ramón , Martin-Gorgojo Alejandro , Suso-Ribera Carlos , Estrada Eduardo , Capriles-Ovalles María-Eugenia , Romero-Brufau Santiago
Published: October 2020

Background: Burnout syndrome is very prevalent among healthcare residents. Initiatives addressing workload conditions have had limited impact on burnout. The present study aims to explore the contribution of two emotion regulation strategies, namely emotion suppression and cognitive reevaluation, to residents’ burnout, while accounting for workload factors. Methods: Participants were 105 residents (68.6% women; mean age = 27.5, SD = 3.0). They completed measures of workload, burnout, and emotion regulation. The study was cross-sectional. Results: Emotional suppression was associated with higher burnout (depersonalization scale; β = 0.20, p < 0.05, CI 0.15–2.48) and cognitive revaluation was linked to lower burnout (higher personal accomplishment; β = 0.35, p < 0.01, CI 0.16–2.56), even after controlling for demographic and workload factors. We found interaction effects between workload variables (supervisor support and number of patient hours) and emotion regulation (p < 0.05). Conclusions: The relationship between workload, emotion regulation, and burnout seems to be complex. That is, similar work conditions might generate different levels of burnout depending on the resident’s emotional regulation strategies. This might partly explain why existing initiatives based on workload changes have had a modest impact on burnout. Results also support including emotion regulation training in prevention and treatment programs targeting burnout during residency.
The Determinants of Conspiracy Beliefs Related to the COVID-19 Pandemic in a Nationally Representative Sample of Internet Users
Authors: Duplaga Mariusz
Published: October 2020

An overwhelming flood of misinformation is accompanying the pandemic of COVID-19. Fake news and conspiracy theories are so prevalent that the World Health Organization started as early as February 2020 to use the term “infodemic”. This paper is focused on the assessment of the prevalence of beliefs in conspiracy theories related to COVID-19 in Polish society. The association of support for conspiracy theories with sociodemographic variables, health literacy (HL) and eHealth literacy (eHL) was studied. The analysis reported here was based on the data from an online survey of a representative sample (n = 1002) of the adult population of Polish Internet users. The multivariate linear regression for the COVID-19-related conspiracy belief score (CCBS) and logistic regression models for the support of individual conspiracy theories was developed. The percentage of supporters of particular conspiracy theories in the study sample ranged from 43% to 56%. The CCBS was significantly associated with age, education level, vocational status and both HL and eHL. However, it was lower for persons with higher HL (regression coefficient (B) = −0.04, p < 0.001) but higher for those with higher eHL (B = 0.04, p = 0.038). The most influential predictors of CCBS were age (standardised regression coefficient (β) = −0.21) and education level (β from 0.08 to 0.16 for respondents with lower education levels and those with master’s degrees). In conclusion, younger persons rather than older, those with a lower rather than with a higher level of education, employees rather than students and persons with lower rather than higher HL were more likely to believe the conspiracy theories. Surprisingly, contrary to expectations, higher eHL was significantly associated with greater belief in such theories.
The Social Support Networks Scale (SSNS) for Family Caregivers of Children with Cancer: A Psychometric Evaluation
Authors: Toledano-Toledano Filiberto , Moral de la Rubia José , Reyes Frometa René , González Betanzos Fabiola , Villavicencio Guzmán Laura , Salazar García Marcela
Published: October 2020

Currently, information about the psychometric properties of the Social Support Networks Scale (SSNS) for family caregivers of children with cancer is not yet available; therefore, there is no empirical evidence of its validity and reliability to support its use in this population. The aim of this study is to determine a factorial model of the SSNS, estimate its internal consistency reliability, describe its distribution, and check its concurrent validity. A convenience sample of 633 family caregivers of children with cancer hospitalized in a National Institute of Health in Mexico City was collected. The SSNS, a sociodemographic variables questionnaire, and three instruments that evaluated family functioning, quality of life, and resilience were applied. The five-factor model had a poor data fit and lacked discriminant validity. The sample was divided. In a subsample of 316 participants, exploratory factor analysis suggested a four-factor model. When testing the four-factor model through confirmatory factor analysis, religious support was independent of family support, friend support, and lack of support. In the other subsample of 317 participants, the one-factor model for religious support had a good fit, and the correlated three-factor model, with the remaining factors, showed an acceptable fit. Reliability ranged from acceptable (Guttman’s λ2 = 0.72) to good (λ2 = 0.88). Socio-family support and its three factors were correlated with family functioning, resilience, and quality of life. Religious support was correlated with four factors of resilience and quality of life. A scale of socio-family support with three factors and an independent scale for religious support are defined from the SSNS, and they showed internal consistency and construct validity.
Soil Bacterial Community Structure in Turfy Swamp and Its Response to Highway Disturbance
Authors: He Yuanyuan , Xu Yan , Lv Yan , Nie Lei , Wang Hong
Published: October 2020

In recent years, the construction and development of highways in turfy swamp areas has been very common. When highways pass through turfy swamps, they can change the local soil, vegetation and hydrological environment, but the impact on soil microorganisms is unclear. We studied the impact of highways on soil microbial communities and diversity in three turfy swamps. Soil samples were collected in the affected area (distance from the expressway 10 m) and control area (distance from the expressway 500–1000 m), and the soil properties, heavy metal content and microbial composition were measured. Subsequent statistical analysis showed that soil organic carbon (SOC), total nitrogen (TN), Cd, Cr, Zn, Cu, density and especially water table (WT) are the main driving forces affecting the composition of microorganisms. The WT and density can also be used to predict the change trend of the ratio of proteobacteria to acid bacteria, reflecting the soil nutrient status. In general, the composition of soil microorganisms in turfy swamp is mainly affected by road drainage and heavy metal emissions. This research provides new insights into the impact of highways on turfy swamps from the perspective of bacterial diversity and community composition, and it also provides a basis for the restoration of the wetland ecological environment.
Multi–Criteria–Decision–Analysis (MCDA) for the Horizon Scanning of Health Innovations an Application to COVID 19 Emergency
Authors: Ruggeri Matteo , Cadeddu Chiara , Roazzi Paolo , Mandolini Donatella , Grigioni Mauro , Marchetti Marco
Published: October 2020

Aim: In this article, we aim to present a tool for the early assessment of medical technologies. This evaluation system was designed and implemented by the National Centre for HTA and the National Centre for Innovative Technologies of the Istituto Superiore di Sanita, Italy, in order to respond to an institutional commitment within the “Health Technologies Assessment Team” that was established to face the huge demand for the evaluation of Health Technologies during the pandemic event caused by COVID-19, with a smart and easy-to-use framework. Methods: Horizon scanning was conducted through a brief assessment carried out according to the multicriteria decision analysis methodology. Each HTA domain was attributed a score according to a pros/cons and opportunities/threats system, derived from evidence in the literature. Scores were weighted according to different perspectives. Scores were presented in a Cartesian graph showing the positioning according to the potential value and the perceived risk associated with the technology. Results: Two case studies regarding the early assessment were reported, concerning two specific technologies: an individual protection device and a contact tracking system.
Does the Registered Dentists’ Program Alleviate the Socioeconomic Gap in the Use of Dental Sealants?
Authors: Jeon Ji-Eun , Lim A-Rang , Park Hyang-Ah , Ryu Jae-In
Published: October 2020

Many countries provide preventive dental care for children to reduce inequalities. In Korea, the registered dentists’ program was implemented to promote oral health and prevent oral diseases in primary school students. This study aimed to evaluate the registered dentist program through the sealant utilization rate using national cohort data and to compare the socioeconomic gap of the cohorts by participation. The sample cohort data were obtained from the National Health Insurance Sharing Service (NHISS) in South Korea. The utilization of dental sealants was analyzed using the chi-square test according to the independent variables of each year. To identify the independent effects of participation in the registered dentists’ program, a panel logistic regression analysis of the utilization of dental sealants was performed. The participants were 1.35 times more likely to have dental sealants than non-participants. The significance of income quintiles disappeared in the case groups. The gap became more obvious in the employees of the control group even after adjusting for all variables. Implementing oral health programs can alleviate inequality with a relative increase in utilization in vulnerable populations.
Participation Motives of Sport and Exercise Maintainers: Influences of Age and Gender
Authors: Ley Clemens
Published: October 2020

Promotion of physical activity has become a global priority for public health. While many people do not adhere to the recommendations, sport and exercise maintainers have found their right or fitting practice. Thus, assessing and knowing the participation motives across maintainers helps to improve our understanding of the sports and exercise practices and, thus, to recommend and to design physical activities and programmes that fit to individuals’ motives. A modified version of the Bernese Motive and Goal Inventory was used in an Austria-wide cross-sectional study with 10646 sport and exercise maintainers (43% female). The study performed confirmatory factor analysis, examined measurement invariance, and compared participation motives. The results showed a good model fit and measurement invariance, indicating that the inventory can be applied independently of gender, age and years of sport/exercise experiences. Motives differed among gender, age and type of sports/exercise. Therefore, these variables should be considered in tailoring sport recommendations and interventions to promote adherence. Finally, the results are discussed by using the Self-Determination Theory indicating that sport and exercise maintainers pursue predominantly motives with intrinsic goal contents.
Spatial and Temporal Evaluation of Ecological Footprint Intensity of Jiangsu Province at the County-Level Scale
Authors: Wu Decun , Liu Jinping
Published: October 2020

Due to the high ecological pressure that exists in the process of rapid economic development in Jiangsu Province, it is necessary to evaluate its ecological footprint intensity (EFI). This article focuses on ecological footprint intensity analysis at the county scale. We used county-level data to evaluate the spatial distributions and temporal trends of the ecological footprint intensity in Jiangsu’s counties from 1995 to 2015. The temporal trends of counties are divided into five types: linear declining type, N-shape type, inverted-N type, U-shape type and inverted-U shape type. It was discovered that the proportions of the carbon footprint intensity were maintained or increased in most counties. Exploratory spatial data analysis shows that there was a certain regularity of the EFI spatial distributions, i.e., a gradient decrease from north to south, and there was a decline in the spatial heterogeneity of EFI in Jiangsu’s counties over time. The global Moran’s index (Moran’s I) and local spatial association index (LISA) are used to analyze both the global and local spatial correlation of EFIs among counties of Jiangsu Province. The high-high and low-low agglomeration effects were the most common, and there were assimilation impacts of counties with strong agglomeration on adjacent units over time. The results implied the utility of differentiated EFI reduction control measures and promotion of low-low agglomeration and suppression of high-high agglomeration in EFI-related ecology policy.
Broadening and Enhancing Bacteriocins Activities by Association with Bioactive Substances
Authors: Zgheib Hassan , Drider Djamel , Belguesmia Yanath
Published: October 2020

Bacteriocins are antimicrobial peptides some of which are endowed with antiviral, anticancer and antibiofilm properties. These properties could be improved through synergistic interactions of these bacteriocins with other bioactive molecules such as antibiotics, phages, nanoparticles and essential oils. A number of studies are steadily reporting the effects of these combinations as new and potential therapeutic strategies in the future, as they may offer many incentives over existing therapies. In particular, bacteriocins can benefit from combination with nanoparticles which can improve their stability and solubility, and protect them from enzymatic degradation, reduce their interactions with other molecules and improve their bioavailability. Furthermore, the combination of bacteriocins with other antimicrobials is foreseen as a way to reduce the development of antibiotic resistance due to the involvement of several modes of action. Another relevant advantage of these synergistic combinations is that it decreases the concentration of each antimicrobial component, thereby reducing their side effects such as their toxicity. In addition, combination can extend the utility of bacteriocins as antiviral or anticancer agents. Thus, in this review, we report and discuss the synergistic effects of bacteriocin combinations as medicines, and also for other diverse applications including, antiviral, antispoilage, anticancer and antibiofilms.
Work Ability Assessment and Its Relationship with Cardiovascular Autonomic Profile in Postural Orthostatic Tachycardia Syndrome
Authors: Barbic Franca , Minonzio Maura , Cairo Beatrice , Shiffer Dana , Zamuner Antonio Roberto , Cavalieri Silvia , Dipaola Franca , Magnavita Nicola , Porta Alberto , Furlan Raffaello
Published: October 2020

Postural orthostatic tachycardia syndrome (POTS) negatively impacts quality of life. The excessive increase in cardiac sympathetic modulation during standing, which characterizes POTS patients, leads to many symptoms and signs of orthostatic intolerance. Little is known about the consequences of the disease on work performance and its relationship with individual autonomic profiles. Twenty-two POTS patients regularly engaged in working activity (20 females, age 36 ± 12 years) and 18 gender- and age-matched controls underwent a clinical evaluation and filled out the Work Ability Index (WAI) questionnaire. POTS patients completed the Composite Autonomic Symptom Score (COMPASS31) questionnaire, underwent continuous electrocardiogram, blood pressure and respiratory activity recordings while supine and during a 75° head-up tilt (HUT). A power spectrum analysis provided the index of cardiac sympatho-vagal balance (LF/HF). WAI scores were significantly reduced in POTS patients (29.84 ± 1.40) compared to controls (45.63 ± 0.53, p < 0.01). A significant inverse correlation was found between individual WAI and COMPASS31 scores (r = −0.46; p = 0.03), HUT increase in heart rate (r = −0.57; p = 0.01) and LF/HF (r = −0.55; p = 0.01). In POTS patients, the WAI scores were inversely correlated to the intensity of autonomic symptoms and to the excessive cardiac sympathetic activation induced by the gravitational stimulus.
Stroke Analysis in Padel According to Match Outcome and Game Side on Court
Authors: Ramón-Llin Jesús , Guzmán José , Martínez-Gallego Rafael , Muñoz Diego , Sánchez-Pay Alejandro , Sánchez-Alcaraz Bernardino J.
Published: October 2020

The aim of this study was to analyze the distribution of padel strokes, their effectiveness, direction, and court zone, comparing between the winning and losing pairs in the match and the playing side of the players. The sample included 8441 strokes corresponding to 1055 points out of a total of nine padel matches in the First National Category. The variables analyzed were type of stroke, court area, effectiveness and directions of the strokes, match outcome, and game side. Matches were analyzed through systematic observation. The results showed that the winning pair made a significantly higher percentage of winners, and cross-court smashes and volleys from the offensive zone. In addition, players on the left side executed a higher percentage of cross-court and winning shots than the players on the right side. Such knowledge may constitute a useful guide in the design of appropriate game strategies and specific training sessions based on the shots that will help players to win the match according to the role of the player and depending on their game side.
The Identification of Precursor Regulation Impact on the Methamphetamine Market and Public Health Indicators in the Czech Republic: Time Series Structural Break Analysis
Authors: Petruželka Benjamin , Barták Miroslav
Published: October 2020

Background: This study provides insight into the impact of methamphetamine precursor regulation, which is considered to be one of the most important tools of supply reduction and a tool with potential public health impact. Methods: It is based on a longitudinal and quasi-experimental design and it investigates the changes of methamphetamine precursor regulation in Czech Republic, which is treated as a natural experiment. The statistical analysis uses features from the generalized fluctuation test framework as well as from the F test framework to estimate structural changes in the methamphetamine-related arrests and nonfatal intoxications time series. Results: The analysis identified structural breaks in the majority of the methamphetamine drug market-related time series in the period related to the tightening of regulation. The results of this study show that methamphetamine precursor regulation was associated with the proliferation of international and organized crime groups and with no change in the overall number of arrests and nonfatal intoxications. Conclusions: The precursor regulation ceteris paribus plausibly leads to the change in drug supply towards more organized groups and to an increasing involvement of foreign nationals at the drug market and is not effective in suppressing the methamphetamine market and in reducing the public health indicator of nonfatal methamphetamine intoxications.
Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach
Authors: Menkovic Iskren , Boutin Michel , Alayoubi Abdulfatah , Mercier François E. , Rivard Georges-Étienne , Auray-Blais Christiane
Published: October 2020

Gaucher disease (GD) is a rare autosomal recessive multisystemic lysosomal storage disorder presenting a marked phenotypic and genotypic variability. GD is caused by a deficiency in the glucocerebrosidase enzyme. The diagnosis of GD remains challenging because of the large clinical spectrum associated with the disease. Moreover, GD biomarkers are often not sensitive enough and can be subject to polymorphic variations. The main objective of this study was to perform a metabolomic study using an ultra-performance liquid chromatography system coupled to a time-of-flight mass spectrometer to identify novel GD biomarkers. Following the analysis of plasma samples from patients with GD, and age- and gender-matched control samples, supervised statistical analyses were used to find the best molecules to differentiate the two groups. Targeted biomarkers were structurally elucidated using accurate mass measurements and tandem mass spectrometry. This metabolomic study was successful in highlighting seven biomarkers associated with GD. Fragmentation tests revealed that these latter biomarkers were lyso-Gb1 (glucosylsphingosine) and four related analogs (with the following modifications on the sphingosine moiety: -C2H4, -H2, -H2+O, and +H2O), sphingosylphosphorylcholine, and N-palmitoyl-O-phosphocholineserine. Based on the plasma biomarker distribution, we suggest the evaluation of this GD biomarker profile, which might facilitate early diagnosis, monitoring, and follow-up of patients.
Coenzyme Q10 Supplementation for the Reduction of Oxidative Stress: Clinical Implications in the Treatment of Chronic Diseases
Authors: Gutierrez-Mariscal Francisco Miguel , Arenas-de Larriva Antonio Pablo , Limia-Perez Laura , Romero-Cabrera Juan Luis , Yubero-Serrano Elena Maria , López-Miranda Jose
Published: October 2020

Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q10 (CoQ10) has been described as having multiple functions, such as oxidant action in the generation of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q10 or Qter®, to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ10 possible in clinical practice.
Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers
Authors: Bucalo Agostino , Rega Federica , Zangrilli Arianna , Silvestri Valentina , Valentini Virginia , Scafetta Giorgia , Marraffa Federica , Grassi Sara , Rogante Elena , Piccolo Arianna , Cucchiara Salvatore , Viola Franca , Bianchi Luca , Ottini Laura , Richetta Antonio
Published: October 2020

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical–pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.
Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo
Authors: Markov Andrey V. , Sen’kova Aleksandra V. , Babich Valeriya O. , Odarenko Kirill V. , Talyshev Vadim A. , Salomatina Oksana V. , Salakhutdinov Nariman F. , Zenkova Marina A. , Logashenko Evgeniya B.
Published: October 2020

Plant-extracted triterpenoids belong to a class of bioactive compounds with pleotropic functions, including antioxidant, anti-cancer, and anti-inflammatory effects. In this work, we investigated the anti-inflammatory and anti-oxidative activities of a semisynthetic derivative of 18βH-glycyrrhetinic acid (18βH-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, or SM) in vitro on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and in vivo in models of acute inflammation: LPS-induced endotoxemia and carrageenan-induced peritonitis. SM used at non-cytotoxic concentrations was found to attenuate the production of reactive oxygen species and nitric oxide (II) and increase the level of reduced glutathione production by LPS-stimulated RAW264.7 cells. Moreover, SM strongly suppressed the phagocytic and migration activity of activated macrophages. These effects were found to be associated with the stimulation of heme oxigenase-1 (HO-1) expression, as well as with the inhibition of nuclear factor-κB (NF-κB) and Akt phosphorylation. Surprisingly, it was found that SM significantly enhanced LPS-induced expression of the pro-inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells via activation of the c-Jun/Toll-like receptor 4 (TLR4) signaling axis. In vivo pre-exposure treatment with SM effectively inhibited the development of carrageenan-induced acute inflammation in the peritoneal cavity, but it did not improve LPS-induced inflammation in the endotoxemia model.
Molecular Manipulation of MicroRNA397 Abundance Influences the Development and Salt Stress Response of Arabidopsis thaliana
Authors: Nguyen Duc Quan , Brown Christopher W. , Pegler Joseph L. , Eamens Andrew L. , Grof Christopher P. L.
Published: October 2020

Arabidopsis thaliana (Arabidopsis) has been used extensively as a heterologous system for molecular manipulation to genetically characterize both dicotyledonous and monocotyledonous plant species. Here, we report on Arabidopsis transformant lines molecularly manipulated to over-accumulate the small regulatory RNA microRNA397 (miR397) from the emerging C4 monocotyledonous grass model species Setaria viridis (S. viridis). The generated transformant lines, termed SvMIR397 plants, displayed a range of developmental phenotypes that ranged from a mild, wild-type-like phenotype, to a severe, full dwarfism phenotype. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR)-based profiling of the SvMIR397 transformant population revealed a strong correlation between the degree of miR397 over-accumulation, repressed LACCASE (LAC) target gene expression, reduced lignin content, and the severity of the developmental phenotype displayed by SvMIR397 transformants. Further, exposure of SvMIR397 transformants to a 7-day regime of salt stress revealed the SvMIR397 transformant lines to be more sensitive to the imposed stress than were wild-type Arabidopsis plants. Taken together, the findings reported here via the use of Arabidopsis as a heterologous system show that the S. viridis miR397 small regulatory RNA is able to repress the expression of three Arabidopsis LAC genes which led to reduced lignin content and increased salt stress sensitivity.
Abnormal NFAT5 Physiology in Duchenne Muscular Dystrophy Fibroblasts as a Putative Explanation for the Permanent Fibrosis Formation in Duchenne Muscular Dystrophy
Authors: Herbelet Sandrine , De Paepe Boel , De Bleecker Jan L.
Published: October 2020

Duchenne muscular dystrophy (DMD) is characterized by chronic inflammation and fibrotic tissue production by fibroblasts. The promyogenic factor nuclear factor of activated T-cells 5 (NFAT5) is virtually present in all cells, responding to hyperosmolar or pro-inflammatory stress. In embryogenic fibroblasts, absence of NFAT5 results in cell cycle arrest. Here, unaffected skeletal muscle fibroblasts from one healthy donor showed NFAT5 nuclear translocation upon hyperosmolar stress and normal cell viability. Absence of NFAT5 translocation under pro-inflammatory conditions resulted in decreased cell growth (Incucyte ZOOM). In DMD skeletal muscle fibroblasts from one DMD patient, NFAT5 was merely located in the nucleus. Exposure to hyperosmolar conditions or pro-inflammatory cytokines IFN-γ, IL-1β and TNF-α had no influence on NFAT5 physiology (immunofluorescence, western blotting, RT-qPCR). Hyperosmolarity resulted in decreased cell viability and pro-inflammatory stress in unaltered cell growth. These findings suggest that NFAT5 is vital to DMD fibroblast survival. Exposure to pro-inflammatory or hyperosmolar stress in DMD fibroblasts results in an unexpected NFAT5 response, where fibroblasts are not triggered by inflammatory cytokines and do not withstand hyperosmolarity. Chronic inflammation could be viewed as a non-restrictive factor in the formation of fibrosis in DMD. Abnormal NFAT5 physiology could provide a molecular explanation for permanent fibrotic matrix production by DMD fibroblasts.
Cisplatin-Induced Giant Cells Formation Is Involved in Chemoresistance of Melanoma Cells
Authors: Weng Chien-Hui , Wu Chieh-Shan , Wu Jian-Ching , Kung Mei-Lang , Wu Ming-Hsiu , Tai Ming-Hong
Published: October 2020

Melanoma is notoriously resistant to current cancer therapy. However, the chemoresistance mechanism of melanoma remains unclear. The present study unveiled that chemotherapy drug cisplatin induced the formation of giant cells, which exhibited enlargement in cell diameter and nucleus in mice and human melanoma cells. Giant cells were positive with melanoma maker S100 and cancer stem cell markers including ABCB5 and CD133 in vitro and in vivo. Moreover, giant cells retained the mitotic ability with expression of proliferation marker Ki-67 and exhibited multiple drug resistance to doxorubicin and actinomycin D. The mitochondria genesis/activities and cellular ATP level were significantly elevated in giant cells, implicating the demand for energy supply. Application of metabolic blockers such as sodium azide or 2-deoxy glucose abolished the cisplatin-induced giant cells formation and expression of cancer stemness markers. The present study unveils a novel chemoresistance mechanism of melanoma cells via size alteration and the anti-neoplastic strategy by targeting giant cells.
Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice
Authors: Ko Il-Gyu , Jin Jun-Jang , Hwang Lakkyong , Kim Sang-Hoon , Kim Chang-Ju , Han Jin Hee , Lee Seunghwan , Kim Ha Il , Shin Hyun Phil , Jeon Jung Won
Published: October 2020

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.
Chemical Starting Matter for HNF4α Ligand Discovery and Chemogenomics
Authors: Meijer Isabelle , Willems Sabine , Ni Xiaomin , Heering Jan , Chaikuad Apirat , Merk Daniel
Published: October 2020

Hepatocyte nuclear factor 4α (HNF4α) is a ligand-sensing transcription factor and presents as a potential drug target in metabolic diseases and cancer. In humans, mutations in the HNF4α gene cause maturity-onset diabetes of the young (MODY), and the elevated activity of this protein has been associated with gastrointestinal cancers. Despite the high therapeutic potential, available ligands and structure–activity relationship knowledge for this nuclear receptor are scarce. Here, we disclose a chemically diverse collection of orthogonally validated fragment-like activators as well as inverse agonists, which modulate HNF4α activity in a low micromolar range. These compounds demonstrate the druggability of HNF4α and thus provide a starting point for medicinal chemistry as well as an early tool for chemogenomics.
High Sensitivity In Vivo Imaging of Cancer Metastasis Using a Near-Infrared Luciferin Analogue seMpai
Authors: Nakayama Jun , Saito Ryohei , Hayashi Yusuke , Kitada Nobuo , Tamaki Shota , Han Yuxuan , Semba Kentaro , Maki Shojiro A.
Published: October 2020

Bioluminescence imaging (BLI) is useful to monitor cell movement and gene expression in live animals. However, D-luciferin has a short wavelength (560 nm) which is absorbed by tissues and the use of near-infrared (NIR) luciferin analogues enable high sensitivity in vivo BLI. The AkaLumine-AkaLuc BLI system (Aka-BLI) can detect resolution at the single-cell level; however, it has a clear hepatic background signal. Here, to enable the highly sensitive detection of bioluminescence from the surrounding liver tissues, we focused on seMpai (C15H16N3O2S) which has been synthesized as a luciferin analogue and has high luminescent abilities as same as AkaLumine. We demonstrated that seMpai BLI could detect micro-signals near the liver without any background signal. The solution of seMpai was neutral; therefore, seMpai imaging did not cause any adverse effect in mice. seMpai enabled a highly sensitive in vivo BLI as compared to previous techniques. Our findings suggest that the development of a novel mutated luciferase against seMpai may enable a highly sensitive BLI at the single-cell level without any background signal. Novel seMpai BLI system can be used for in vivo imaging in the fields of life sciences and medicine.