bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges Affecting Access to Health and Social Care Resources and Time Management among Parents of Children with Rett Syndrome: A Qualitative Case Study
Authors: Güeita-Rodriguez Javier , Famoso-Pérez Pilar , Salom-Moreno Jaime , Carrasco-Garrido Pilar , Pérez-Corrales Jorge , Palacios-Ceña Domingo
Published: June 2020

Rare diseases face serious sustainability challenges regarding the distribution of resources geared at health and social needs. Our aim was to describe the barriers experienced by parents of children with Rett Syndrome for accessing care resources. A qualitative case study was conducted among 31 parents of children with Rett syndrome. Data were collected through in-depth interviews, focus groups, researchers’ field notes and parents’ personal documents. A thematic analysis was performed and the Standards for Reporting Qualitative Research (SRQR) guidelines were followed. Three main themes emerged from the data: (a) essential health resources; (b) bureaucracy and social care; and (c) time management constraints. Parents have difficulties accessing appropriate health services for their children. Administrative obstacles exist for accessing public health services, forcing parents to bear the financial cost of specialized care. Time is an essential factor, which conditions the organization of activities for the entire family. Qualitative research offers insight into how parents of children with Rett syndrome experience access to resources and may help improve understanding of how Rett syndrome impacts the lives of both the children and their parents.
Mutation in ROBO3 Gene in Patients with Horizontal Gaze Palsy with Progressive Scoliosis Syndrome: A Systematic Review
Authors: Pinero-Pinto Elena , Pérez-Cabezas Verónica , Tous-Rivera Cristina , Sánchez-González José-María , Ruiz-Molinero Carmen , Jiménez-Rejano José-Jesús , Benítez-Lugo María-Luisa , Sánchez-González María Carmen
Published: June 2020

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movements with progressive scoliosis developing in childhood and adolescence. Mutations in the Roundabout (ROBO3) gene located on chromosome 11q23–25 are responsible for the development of horizontal gaze palsy and progressive scoliosis. However, some studies redefined the locus responsible for this pathology to a 9-cM region. This study carried out a systematic review in which 25 documents were analyzed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was made in the following electronic databases from January 1995 to October 2019: PubMed, Scopus, Web of Science, PEDRO, SPORT Discus, and CINAHL. HGPPS requires a multidisciplinary diagnostic approach, in which magnetic resonance imaging might be the first technique to suggest the diagnosis, which should be verified by an analysis of the ROBO3 gene. This is important to allow for adequate ocular follow up, apply supportive therapies to prevent the rapid progression of scoliosis, and lead to appropriate genetic counseling.
Sexual Dysfunction in Young Women with Type 1 Diabetes
Authors: Cichocka Edyta , Jagusiewicz Michał , Gumprecht Janusz
Published: June 2020

Introduction: Sexual dysfunctions (SD) are chronic complications that can develop due to vascular complications or autonomic neuropathy. Additionally, such complications can be of hormonal, infectious or psychogenic etiology. Objectives: The aim of study was to assess the sexual function and acceptance of the chronic disease in young sexually active women with type 1 diabetes (T1DM). Materials and methods: A total of 169 female patients with T1DM completed two standardized questionnaires, the Female Sexual Function Index (FSFI) and the Acceptance of Illness Scale (AIS). Other medical data were collected from medical history. Results: The mean FSFI score was 27.96 ± 5.00, and the mean AIS score was 29.67 ± 8.28. The score < 26 points in FSFI was obtained by 28.7% of patients. Analysis of correlation between the FSFI and the AIS showed that the higher the score on the FSFI, the higher the score on the AIS. Patients who underwent regular physical activity (55%) had a significantly higher acceptance of the disease (p = 0.0026) and reported painful intercourse significantly less frequently (p = 0.01). The value of HbA1c in the study group was 7.31 ± 1.25%. Patients with poorer glycemic control (HbA1c > 8%) obtained significantly lower scores on the FSFI (p = 0.03), whereas no differences were found on the AIS. Diabetes-related complications were observed in 25.5% of patients. The presence of chronic complications did not affect the results of the FSFI or the AIS. Patients with diabetes and hypertension had poorer functioning in the sexual sphere and had significantly lower scores on the FSFI. Past or present history of depression was reported by 36% of patients and also negatively affected acceptance of diabetes (p = 0.0015). Patients who reported recurrent urinary tract infections (17%) achieved significantly lower scores on the FSFI (p = 0.03) and showed that sex-related pain was significantly more prevalent (p = 0.02). In the case of the statement related to the embarrassment of people around the patient due to diabetes, patients with lower scores complained of SD significantly more often (p = 0.0033). Past deliveries, the type of labor, the use of contraceptives or the number of sexual partners had no influence on the overall assessment in both scales. However, in terms of desire, women who had delivered obtained higher scores (p = 0.0021). Conclusion: SD in women with T1DM may result from diabetes-related complications, hormonal disorders or recurrent genital or urinary tract infections. However, they usually have a psychological basis due to the lack of acceptance of the problems related to the treatment of diabetes.
Understanding the Phenomenon of Binge-Watching—A Systematic Review
Authors: Starosta Jolanta A. , Izydorczyk Bernadetta
Published: June 2020

Binge-watching is a relatively new behaviour pattern whose popularity has been increasing since 2013, ultimately to become one of the most popular ways of spending free time, especially among young people. However, there is still a dearth of research on this phenomenon. The aim of this study is to present the current understanding and psychological conditions of binge-watching, as provided in the research papers published between 2013 and 2020. This systematic review, including 28 articles, addresses different approaches to defining this behaviour, diverse motivations, personality traits, and risks of excessive binge-watching. Its results imply that there are two perspectives in understanding binge-watching. The first is related to entertainment, positive emotions, cognition, and spending free time. However, the second perspective emphasises the negative outcomes of excessive binge-watching and symptoms of behavioural addiction. There is undoubtedly a need for further research to be conducted on diversified populations to reach more profound understanding of binge-watching behaviour patterns.
The Impact of Internet Usage and Knowledge-Intensive Activities on Households’ Healthcare Expenditures
Authors: Benvenuto Marco , Avram Alexandru , Sambati Francesco Vincenzo , Avram Marioara , Viola Carmine
Published: June 2020

This paper examines the impact of the internet usage and knowledge intensive activities on households’ healthcare expenditures Similarly, the paper aims to recognize and understand, from a value-creation perspective, the correlation between: internet access of households (IA), individuals frequently using the internet (IU), individuals searching on internet for health-related information (HI), payments made by households for healthcare (PHH), expressed as euro per inhabitant and employment in knowledge-intensive activities (KIA). The approach utilized in the present study consists of two steps. First, a theoretical framework was conducted to determine the existing relationship between major variables. Next, the Vector Autoregressive (VAR) approach was applied in a case study at European level to prove the three hypothesis we consider. By analyzing the connection between the major variables, a positive and long- lasting impulse response function was revealed, followed by an ascending trend. This suggests that a self-multiplying effect is being generated; and it reasonable to assume that the more individuals use the Internet, the more electronic acquisitions occur. We can thus reasonably conclude that the improvement of the internet usage and knowledge intensive activities on households’ healthcare expenditures process is strongly dependent on people’s capability. Improving IU and KIA is the new reading key in the decision-making process in health system approach.
Community Perceptions of a Multilevel Sanitation Behavior Change Intervention in Rural Odisha, India
Authors: De Shay Renee , Comeau Dawn L. , Sclar Gloria D. , Routray Parimita , Caruso Bethany A.
Published: June 2020

While latrine coverage is increasing in India, not all household members use their latrines. Cost-effective, culturally appropriate, and theory-informed behavior change interventions are necessary to encourage sustained latrine use by all household members. We qualitatively examined community perceptions of sanitation interventions broadly, along with specific impressions and spillover of community-level activities of the Sundara Grama latrine use behavior change intervention in rural Odisha, India. We conducted sixteen sex-segregated focus group discussions (n = 152) in three intervention and three nonintervention villages and thematically analyzed the data. We found Sundara Grama was well-received by community members and considered educative, but perceptions of impact on latrine use were mixed and varied by activity. Intervention recruitment challenges prevented some, such as women and households belonging to lower castes, from attending activities. Spillover occurred in one of two nonintervention villages, potentially due to positive relations within and between the nonintervention village and nearby intervention village. Community-level sanitation initiatives can be hindered by community divisions, prioritization of household sanitation over community cleanliness, and perceptions of latrine use as a household and individual issue, rather than common good. Community-centered sanitation interventions should assess underlying social divisions, norms, and perceptions of collective efficacy to adapt intervention delivery and activities.
Benefits of Physical Activity and Its Associations with Resilience, Emotional Intelligence, and Psychological Distress in University Students from Southern Spain
Authors: San Román-Mata Silvia , Puertas-Molero Pilar , Ubago-Jiménez José Luis , González-Valero Gabriel
Published: June 2020

This is a descriptive and cross-sectional study in a sample of 1095 university students from southern Spain. The aim was to identify the frequency of health-fulfilling physical activity engagement reported by participants. Sufficient physical activity was categorized according to whether participants ‘achieved minimum recommendations’ (≥150 min of moderate physical activity) or ‘did not achieve minimum recommendations’ (≤150 min of moderate physical activity). Participants were further categorized as: inactive (does not engage in physical activity or sport), engaging in physical activity that is not beneficial to health (≤300 min of moderate physical activity per week) and engaging in physical activity that is beneficial to health (≥300 min of moderate physical activity per week). Possible relationships with psychosocial factors and perceived psychological distress were explored. An ad hoc questionnaire was used to record the time in minutes of physical activity engagement per week. The Connor–Davidson Resilience Scale, the Trait Meta-mood Scale, and Kessler Psychological Distress Scale were also administered. Statically significant differences are shown between the three examined groups: physical inactivity and non-beneficial physical activity; physical inactivity and beneficial physical activity, and; non-beneficial physical activity and beneficial physical activity. Positive and direct correlations were seen with respect to resilience and understanding, and emotional regulation, in addition to negative associations with respect to psychological distress. In conclusion, the more individuals engage in beneficial physical activity, the greater their resilience and emotional management, and the lower their rates of psychological distress.
Effects of Gender and Age on Dietary Intake and Body Mass Index in Hypertensive Patients: Analysis of the Korea National Health and Nutrition Examination
Authors: Dan Hyunju , Kim Jiyoung , Kim Oksoo
Published: June 2020

Controlling weight and dietary intake are important for hypertensive patients to manage their blood pressure. However, the interaction effect of gender and age on weight and dietary intake is not well known. The aim of this study was to examine the main and interaction effects of age and gender on body mass index (BMI) and dietary intake in hypertensive patients. We analyzed data from 4287 participants with hypertension (1600 participants 45–64 years old and 2687 participants 65 years or older) who participated in the Korea National Health and Nutrition Examination Survey (2013–2016). Two-way ANOVAs were conducted to examine the main and interaction effects of age and gender on BMI and dietary intake. Gender and age had significant main effects on BMI, intake of energy, cholesterol, sodium, and potassium. However, both gender and age illustrated interaction effects on BMI (F = 8.398, p = 0.004), energy intake (F = 12.882, p < 0.001), and cholesterol intake (F = 6.107, p = 0.014), while not showing any significant interaction effects on sodium (F = 3.547, p = 0.060) and potassium (F = 3.396, p = 0.066). Compared to the middle-aged group, BMI, energy intake, and cholesterol intake decreased in the older-aged group. However, the declines were steeper in men than in women. Therefore, both gender and age need to be considered for weight and dietary intake management for hypertensive patients.
Proposal of Sustainability Indicators for the Design of Small-Span Bridges
Authors: Milani Cleovir José , Yepes Víctor , Kripka Moacir
Published: June 2020

The application of techniques to analyze sustainability in the life cycle of small-span bridge superstructures is presented in this work. The objective was to obtain environmental and economic indicators for integration into the decision-making process to minimize the environmental impact, reduce resource consumption and minimize life cycle costs. Twenty-seven configurations of small-span bridges (6 to 20 m) of the following types were analyzed: steel–concrete composite bridges, cast in situ reinforced concrete bridges, precast bridges and prestressed concrete bridges, comprising a total of 405 structures. Environmental impacts and costs were quantified via life cycle environmental assessment and life cycle cost analysis following the boundaries of systems from the extraction of materials to the end of bridge life (“from cradle to grave”). In general, the results indicated that the environmental performance of the bridges was significantly linked to the material selection and bridge configuration. In addition, the study enabled the identification of the products and processes with the greatest impact in order to subsidize the design of more sustainable structures and government policies.
The Analysis of Green Areas’ Accessibility in Comparison with Statistical Data in Poland
Authors: Wysmułek Joanna , Hełdak Maria , Kucher Anatolii
Published: June 2020

The study discusses the problem of public green areas’ accessibility for the residents of large cities in Poland. The purpose of the research is to assess the possibility of applying the British Accessible Natural Greenspace Standard (ANGSt) method in determining the amount of natural green space available to residents in Polish conditions including, in particular, the assessment of accessibility using data collected by the Central Statistical Office and the verification of results based on detailed research. The identification of green areas for 18 voivodeship cities in Poland was prepared using the GIS programme, taking into account public green space, provided for general access and free of change. The verification of the ANGSt method consisted of mapping spatial barriers extending the route of access either on foot or by roads as well as closed private areas. The conducted research revealed that, after taking into account the access routes to selected areas, the distance to public green areas increased, on average, from 50 m in the smallest cities (Gorzów Wielkopolski and Olsztyn) to as much as 450 m in Warszawa. A detailed analysis showed that the discussed accessibility was reduced, on average, by almost 10% for the residents of the analysed cities. It was also found that the introduced barriers did not affect the accessibility of more distant, larger green space areas.
Association between Sports-Related Concussion and Mouthguard Use among College Sports Players: A Case-Control Study Based on Propensity Score Matching
Authors: Ono Yoshiaki , Tanaka Yuto , Sako Kazuki , Tanaka Masahiro , Fujimoto Junya
Published: June 2020

Sports-related concussion (SRC) is a major public health concern. This study aimed to assess the association between mouthguard use and the incidence of SRC in college students through a case-control study using propensity score matching. In total, 195 of 2185 potential participants volunteered to participate in this study. We used Google Forms online to capture participants’ information, including: age; gender; height; weight; sports contact level; level of play; exposure time; frequency of mouthguard use; mouthguard type; and SRC experience. Data for 115 participants who played collision and contact sports were used for the analysis. The difference in the frequency of mouthguard use was assessed between matched pairs and the overall association between SRC and mouthguard use was evaluated. In the matched groups, those who had not experienced SRC wore a mouthguard more frequently than those who had experienced SRC (7/28 vs. 1/28; p = 0.051). Logistic regression analysis showed there was a significant negative association between the frequency of mouthguard use and the incidence of SRC (odds ratio 0.101; p = 0.041). Within the limitations of this study, these results suggest that mouthguard use may offer some benefit in preventing SRC.
Development of a Scale for Assessing the Meaning of Participation in Care Prevention Group Activities Provided by Local Governments in Japan
Authors: Sasaki Ryu , Hirano Michiyo
Published: June 2020

The meaning of participation in care prevention group activities may encourage continuous participation, making older adults active and healthy throughout their lives. This study developed a scale to assess the meaning of participation in care prevention group activities. It involved 427 participants in care prevention group activities (CPGAs) in Japan who filled out a self-administered questionnaire between October 2017 and February 2018. The meaning of participation was assessed using 15 items. In total, there were 379 valid responses. A factor analysis yielded two factors: “promotion of self-growth” and “enrichment of daily life”. The goodness of fit index (GFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA) were satisfactory (GFI = 0.923; CFI = 0.960; RMSEA = 0.073). Cronbach’s α was 0.939 for the entire scale. The scale scores were significantly correlated with scores of the social activity-related daily life satisfaction scale and Ikigai-9. The scale’s reliability and validity were confirmed, indicating its usability for promoting care prevention efforts.
Association between Reflux Esophagitis Incidence and Palmar Hyperhidrosis
Authors: Cheng Chun-Gu , Chien Wu-Chien , Yu Chia-Peng , Chung Chi-Hsiang , Cheng Chun-An
Published: June 2020

The autonomic dysfunction in palmar hyperhidrosis (PH) includes not only sympathetic overactivity but also parasympathetic impairment. A decrease of parasympathetic tone has been noted in gastroesophageal reflux disease of neonates and adults. Patients with reflux esophagitis have a defective anti-reflux barrier. The association between reflux esophagitis and PH is deliberated in this article. The National Health Insurance Database in Taiwan was used. At first-time visits, PH patients were identified by the International Classification of Disease, 9th Revision, Clinical Modification disease code of 780.8 without endoscopic thoracic sympathectomy. Patients were matched by age and gender as control groups. The reflux esophagitis incidence was assessed using disease codes 530.11, 530.81, and 530.85. The factors related to reflux esophagitis were established by the Cox proportional regression model. The risk of reflux esophagitis in PH patients had a hazard ratio of 3.457 (95% confidence interval: 3.043–3.928) after adjustment of the other factors. We confirmed the association between reflux esophagitis and PH. Health care providers must be alerted to this relationship and other risk factors of reflux esophagitis to support suitable treatments to improve the quality of life of patients.
Guaranteed Equal Opportunities? The Access to Nursing Training in Central Europe for People with a Turkish Migration Background
Authors: Keckeis Julia , Schäfer Margit , Akkaya-Kalayci Türkan , Löffler-Stastka Henriette
Published: June 2020

This paper examines the reason for the small percentage of professional nurses with a Turkish migration background and investigates possibilities to increase this low amount. Our society grows older, and the number of chronic diseases increases. Furthermore, nursing professionals tend to migrate, and the retirement of the baby boomer generation will also create a lack of professional nurses in Vorarlberg, Austria. People with a Turkish migration background, who are the second largest group without Austrian citizenship in Austria, could be an important resource for the upcoming lack of qualified nurses. The nursing profession could be a secure career opportunity for these people, and therefore it is of great importance to make access to professional nursing training easier for people with a Turkish migration background. This paper describes the effects of migration on society, institutions and individuals and gives an overview of concepts related to how to deal with this situation. This qualitative study investigates the access to nursing training for people with a Turkish migration background from three different points of view—those of experts, students and nurses with a Turkish migration background, and people with a Turkish migration background who have to pass a university entrance qualification—in the form of guided interviews. The results will illustrate structural and social barriers due to complex social dynamics and also highlight possibilities to reduce those barriers. Based on the results, prospects for professional nursing are deduced on the macro, meso and micro levels, which should generate an increasing number of nurses with a Turkish migration background.
Business Results and Well-Being: An Engaging Leadership Intervention Study
Authors: van Tuin Lars , Schaufeli Wilmar B. , van Rhenen Willem , Kuiper Rebecca M.
Published: June 2020

The present quasi-experimental study tested the business impact of a leadership development program focusing on psychological well-being through the satisfaction of basic psychological needs. Based on the concept of engaging leadership and self-determination theory, the 8-month program targeted midlevel team leaders of the customer fulfilment center of a health systems multinational organization. The program was designed in co-creation between senior leadership and the team leaders that participated in the program. Outcomes showed positive business results through significant increases in a preselected key performance indicator and decreased employee absenteeism. Through changes in autonomy satisfaction and intrinsic motivation, the team leaders (N = 14) benefitted in a moderate to very large extent relative to a similar control group (N = 52). In contrast, team members (N = 148) displayed no such benefits. Specifically, higher levels of autonomy satisfaction are said to lead to higher levels of psychological well-being and motivation. Still, the link with business performance is absent in most organizational studies within self-determination theory, making the present study one of the first to fill this gap. The study discloses the program design, compares the effects to a relevant control group, evaluates the lessons learned, and provides practical suggestions.
Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition
Authors: Hraběta Jan , Belhajová Marie , Šubrtová Hana , Merlos Rodrigo Miguel Angel , Heger Zbyněk , Eckschlager Tomáš
Published: June 2020

Resistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.
Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs
Authors: Toptan Tuna , Hoehl Sebastian , Westhaus Sandra , Bojkova Denisa , Berger Annemarie , Rotter Björn , Hoffmeier Klaus , Cinatl Jindrich , Ciesek Sandra , Widera Marek
Published: June 2020

The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Meanwhile, increased demand for testing has led to a shortage of reagents and supplies and compromised the performance of diagnostic laboratories in many countries. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) recommend multi-step RT-PCR assays using multiple primer and probe pairs, which might complicate the interpretation of the test results, especially for borderline cases. In this study, we describe an alternative RT-PCR approach for the detection of SARS-CoV-2 RNA that can be used for the probe-based detection of clinical isolates in diagnostics as well as in research labs using a low-cost SYBR green method. For the evaluation, we used samples from patients with confirmed SARS-CoV-2 infections and performed RT-PCR assays along with successive dilutions of RNA standards to determine the limit of detection. We identified an M-gene binding primer and probe pair highly suitable for the quantitative detection of SARS-CoV-2 RNA for diagnostic and research purposes.
Effect of SOX2 Repression on Corneal Endothelial Cells
Authors: Hwang Jin Sun , Yi Ho Chul , Shin Young Joo
Published: June 2020

Purpose: Human corneal endothelial cells (hCECs) pump out water from the stroma and maintain the clarity of the cornea. The sex-determining region Y-box 2 (SOX2) participates in differentiation during the development of the anterior segment of the eye and is found in the periphery of wounded corneas. This study was performed to investigate the effect of SOX2 repression on hCECs. Methods: Cultured hCECs were transfected by siRNA for SOX2. The wound healing rate and cell viability were measured. The cell proliferation-associated protein level was evaluated by Western blotting and RT-PCR. The energy production and mitochondrial function were measured, and cell shape and WNT signaling were assessed. Results: Upon transfecting the cultured cells with siRNA for SOX2, the SOX2 level was reduced by 80%. The wound healing rate and viability were also reduced. Additionally, CDK1, cyclin D1, SIRT1, and ATP5B levels were reduced, and CDKN2A and pAMPK levels were increased. Mitochondrial oxidative stress and mitochondrial viability decreased, and the cell shape became elongated. Furthermore, SMAD1, SNAI1, WNT3A, and β-catenin levels were increased. Conclusion: SOX2 repression disrupts the normal metabolism of hCECs through modulating WNT signaling and mitochondrial functions.
Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
Authors: Chou Kang-Ju , Hsu Chih-Yang , Huang Chien-Wei , Chen Hsin-Yu , Ou Shih-Hsiang , Chen Chien-Liang , Lee Po-Tsang , Fang Hua-Chang
Published: June 2020

We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-β and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization.
Computational Insights on the Mechanism of the Chemiluminescence Reaction of New Group of Chemiluminogens—10-Methyl-9-thiophenoxycarbonylacridinium Cations
Authors: Pieńkos Milena , Zadykowicz Beata
Published: June 2020

Immunodiagnostics, in which one of the promising procedures is the chemiluminescent labelling, is essential to facilitate the detection of infections in a human organism. One of the standards commonly used in luminometric assays is luminol, which characterized by low quantum yield in aqueous environments. Acridinium esters have better characteristics in this topic. Therefore, the search for new derivatives, especially those characterized by the higher quantum yield of chemiluminescence, is one of the aims of the research undertaken. Using the proposed mechanism of chemiluminescence, we examined the effect of replacing a single atom within a center of reaction on the efficient transformation of substrates into electronically excited products. The density functional theory (DFT) and time dependent (TD) DFT calculated thermodynamic and kinetic data concerning the chemiluminescence and competitive dark pathways suggests that some of the scrutinized derivatives have better characteristics than the chemiluminogens used so far. Synthesis of these candidates for efficient chemiluminogens, followed by studies of their chemiluminescent properties, and ultimately in chemiluminescent labelling, are further steps to confirm their potential applicability in immunodiagnostics.
Vernonia calvoana Shows Promise towards the Treatment of Ovarian Cancer
Authors: Mbemi Ariane T. , Sims Jennifer N. , Yedjou Clement G. , Noubissi Felicite K. , Gomez Christian R. , Tchounwou Paul B.
Published: June 2020

The treatment for ovarian cancers includes chemotherapies which use drugs such as cisplatin, paclitaxel, carboplatin, platinum, taxanes, or their combination, and other molecular target therapies. However, these current therapies are often accompanied with side effects. Vernonia calvoana (VC) is a valuable edible medicinal plant that is widespread in West Africa. In vitro data in our lab demonstrated that VC crude extract inhibits human ovarian cancer cells in a dose-dependent manner, suggesting its antitumor activity. From the VC crude extract, we have generated 10 fractions and VC fraction 7 (F7) appears to show the highest antitumor activity towards ovarian cancer cells. However, the mechanisms by which VC F7 exerts its antitumor activity in cancer cells remain largely unknown. We hypothesized that VC F7 inhibits cell proliferation and induces DNA damage and cell cycle arrest in ovarian cells through oxidative stress. To test our hypothesis, we extracted and fractionated VC leaves. The effects of VC F7 were tested in OVCAR-3 cells. Viability was assessed by the means of MTS assay. Cell morphology was analyzed by acridine orange and propidium iodide (AO/PI) dye using a fluorescent microscope. Oxidative stress biomarkers were evaluated by the means of lipid peroxidation, catalase, and glutathione peroxidase assays, respectively. The degree of DNA damage was assessed by comet assay. Cell cycle distribution was assessed by flow cytometry. Data generated from the MTS assay demonstrated that VC F7 inhibits the growth of OVCAR-3 cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VC F7-treated cells. Data obtained from the AO/PI dye assessment revealed morphological alterations and exhibited characteristics such as loss of cellular membrane integrity, cell shrinkage, cell membrane damage, organelle breakdown, and detachment from the culture plate. We observed a significant increase (p < 0.05) in the levels of malondialdhyde (MDA) production in treated cells compared to the control. A gradual decrease in both catalase and glutathione peroxidase activities were observed in the treated cells compared to the control. Data obtained from the comet assay showed a significant increase (p < 0.05) in the percentages of DNA cleavage and comet tail length. The results of the flow cytometry analysis indicated VC F7 treatment caused cell cycle arrest at the S-phase checkpoint. Taken together, our results demonstrate that VC F7 exerts its anticancer activity by inhibiting cell proliferation, inducing DNA damage, and causing cell cycle arrest through oxidative stress in OVAR-3 cells. This finding suggests that VC F7 may be a potential alternative dietary agent for the prevention and/or treatment of ovarian cancer.
PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation
Authors: Hirohama Daigoro , Kawarazaki Wakako , Nishimoto Mitsuhiro , Ayuzawa Nobuhiro , Marumo Takeshi , Shibata Shigeru , Fujita Toshiro
Published: June 2020

Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.
Molecular Epidemiology of B3 and D8 Measles Viruses through Hemagglutinin Phylogenetic History
Authors: Bianchi Silvia , Canuti Marta , Ciceri Giulia , Gori Maria , Colzani Daniela , Dura Marco , Pennati Beatrice Marina , Baggieri Melissa , Magurano Fabio , Tanzi Elisabetta , Amendola Antonella
Published: June 2020

Of the 24 known measles genotypes, only D8 and B3 are responsible for outbreaks in the last years in Europe, Asia, and America. In this study the H gene of 92 strains circulating between 2015 and 2019 in Lombardy, Northern Italy, and 1273 H sequences available in GenBank were analyzed in order to evaluate the genetic variability and to assess the conservation of the immunodominant sites. Overall, in Lombardy we observed the presence of four different B3 and three different D8 clusters, each one of them including sequences derived from viruses found in both vaccinated and unvaccinated subjects. Worldwide, the residue 400 within the H protein, a position located within the main immune epitope, is mutated in all circulating strains that belong to the two globally endemic genotypes, B3 and D8. Our data demonstrate the usefulness of measles virus (MV) H gene sequencing. Indeed, the monitoring the H protein epitopes of circulating strains could be included in the measles laboratory surveillance activities in order to improve and optimize strategies for measles control, as countries go towards elimination phase.
The Genome Analysis of Methylobacterium populi YC-XJ1 with Diverse Xenobiotics Biodegrading Capacity and Degradation Characteristics of Related Hydrolase
Authors: Li Xianjun , Wang Junhuan , Jia Yang , Reheman Aikebaier , Yan Yanchun
Published: June 2020

Methylobacterium populi YC-XJ1 isolated from desert soil exhibited a diverse degrading ability towards aromatic oxyphenoxypropionic acid esters (AOPPs) herbicide, phthalate esters (PAEs), organophosphorus flame retardants (OPFRs), chlorpyrifos and phoxim. The genome of YC-XJ1 was sequenced and analyzed systematically. YC-XJ1 contained a large number of exogenous compounds degradation pathways and hydrolase resources. The quizalofop-p-ethyl (QPE) degrading gene qpeh2 and diethyl phthalate (DEP) degrading gene deph1 were cloned and expressed. The characteristics of corresponding hydrolases were investigated. The specific activity of recombinant QPEH2 was 0.1 ± 0.02 U mg−1 for QPE with kcat/Km values of 1.8 ± 0.016 (mM−1·s−1). The specific activity of recombinant DEPH1 was 0.1 ± 0.02 U mg−1 for DEP with kcat/Km values of 0.8 ± 0.02 (mM−1·s−1). This work systematically illuminated the metabolic versatility of strain YC-XJ1 via the combination of genomics analysis and laboratory experiments. These results suggested that strain YC-XJ1 with diverse xenobiotics biodegrading capacity was a promising candidate for the bioremediation of polluted sites.
Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy
Authors: Ginefra Pierpaolo , Lorusso Girieca , Vannini Nicola
Published: June 2020

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.
Regulation of GABAA Receptor Subunit Expression in Substance Use Disorders
Authors: Barker Jeffrey , Hines Rochelle
Published: June 2020

The modulation of neuronal cell firing is mediated by the release of the neurotransmitter GABA (γ-aminobuytric acid), which binds to two major families of receptors. The ionotropic GABAA receptors (GABAARs) are composed of five distinct subunits that vary in expression by brain region and cell type. The action of GABA on GABAARs is modulated by a variety of clinically and pharmacologically important drugs such as benzodiazepines and alcohol. Exposure to and abuse of these substances disrupts homeostasis and induces plasticity in GABAergic neurotransmission, often via the regulation of receptor expression. Here, we review the regulation of GABAAR subunit expression in adaptive and pathological plasticity, with a focus on substance use. We examine the factors influencing the expression of GABAAR subunit genes including the regulation of the 5′ and 3′ untranslated regions, variations in DNA methylation, immediate early genes and transcription factors that regulate subunit expression, translational and post-translational modifications, and other forms of receptor regulation beyond expression. Advancing our understanding of the factors regulating GABAAR subunit expression during adaptive plasticity, as well as during substance use and withdrawal will provide insight into the role of GABAergic signaling in substance use disorders, and contribute to the development of novel targeted therapies.
Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome
Authors: Lazo Pedro A. , García Juan L. , Gómez-Puertas Paulino , Marcos-Alcalde Íñigo , Arjona Cesar , Villarroel Alvaro , González-Sarmiento Rogelio , Fons Carmen
Published: June 2020

Complex neurodevelopmental syndromes frequently have an unknown etiology, in which genetic factors play a pathogenic role. This study utilizes whole-exome sequencing (WES) to examine four members of a family with a son presenting, since birth, with epileptic-like crises, combined with cerebral palsy, severe neuromotor and developmental delay, dystonic tetraparexia, axonal motor affectation, and hyper-excitability of unknown origin. The WES study detected within the patient a de novo heterozygous in-frame duplication of thirty-six nucleotides within exon 7 of the human KCNQ2 gene. This insertion duplicates the first twelve amino acids of the calmodulin binding site I. Molecular dynamics simulations of this KCNQ2 peptide duplication, modelled on the 3D structure of the KCNQ2 protein, suggest that the duplication may lead to the dysregulation of calcium inhibition of this protein function.
Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis
Authors: Adekoya Timothy O. , Richardson Ricardo M.
Published: June 2020

The consequences of prostate cancer metastasis remain severe, with huge impact on the mortality and overall quality of life of affected patients. Despite the convoluted interplay and cross talk between various cell types and secreted factors in the metastatic process, cytokine and chemokines, along with their receptors and signaling axis, constitute important factors that help drive the sequence of events that lead to metastasis of prostate cancer. These proteins are involved in extracellular matrix remodeling, epithelial-mesenchymal-transition, angiogenesis, tumor invasion, premetastatic niche creation, extravasation, re-establishment of tumor cells in secondary organs as well as the remodeling of the metastatic tumor microenvironment. This review presents an overview of the main cytokines/chemokines, including IL-6, CXCL12, TGFβ, CXCL8, VEGF, RANKL, CCL2, CX3CL1, IL-1, IL-7, CXCL1, and CXCL16, that exert modulatory roles in prostate cancer metastasis. We also provide extensive description of their aberrant expression patterns in both advanced disease states and metastatic sites, as well as their functional involvement in the various stages of the prostate cancer metastatic process.
Tooth Enamel and Its Dynamic Protein Matrix
Authors: Gil-Bona Ana , Bidlack Felicitas B.
Published: June 2020

Tooth enamel is the outer covering of tooth crowns, the hardest material in the mammalian body, yet fracture resistant. The extremely high content of 95 wt% calcium phosphate in healthy adult teeth is achieved through mineralization of a proteinaceous matrix that changes in abundance and composition. Enamel-specific proteins and proteases are known to be critical for proper enamel formation. Recent proteomics analyses revealed many other proteins with their roles in enamel formation yet to be unraveled. Although the exact protein composition of healthy tooth enamel is still unknown, it is apparent that compromised enamel deviates in amount and composition of its organic material. Why these differences affect both the mineralization process before tooth eruption and the properties of erupted teeth will become apparent as proteomics protocols are adjusted to the variability between species, tooth size, sample size and ephemeral organic content of forming teeth. This review summarizes the current knowledge and published proteomics data of healthy and diseased tooth enamel, including advancements in forensic applications and disease models in animals. A summary and discussion of the status quo highlights how recent proteomics findings advance our understating of the complexity and temporal changes of extracellular matrix composition during tooth enamel formation.
Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease
Authors: Baragetti Andrea , Catapano Alberico Luigi , Magni Paolo
Published: June 2020

Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1β) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1β pathway.