bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Management after a Therapeutic Education Program: A Qualitative Study
Authors: Romero-Castillo Rocío , Pabón-Carrasco Manuel , Jiménez-Picón Nerea , Ponce-Blandón José Antonio
Published: July 2022

(1) Background: Structured education has been used in patients treated with insulin, promoting their ability to adhere to and self-manage their treatment. We aimed to know the perception and adherence to the recommendations on the management of diabetes in type 1 diabetes patients after participating in a therapeutic education program. (2) Methods: A descriptive qualitative study followed the Standards for Reporting Qualitative Research guidelines. Patients with type 1 diabetes participating in a therapeutic education program were recruited from February to April 2022. Semi-structured, in-depth interviews were used, and transcriptions were analyzed using the inductive qualitative content analysis method. The final sample consisted of 18 type 1 diabetes mellitus patients. (3) Results: A number of patients with type 1 diabetes said that they had improved their glycemic control after participating in the therapeutic education program. Some patients recognized that the chronic disease and the complications complexity generated stress and anxiety. This influenced their usual life, at work, and their interpersonal relationships. (4) Conclusions: In terms of satisfaction, the majority of patients reported a good perception of the quality of the organization, the professionals involved, and the contents of the program. The physical and psychosocial benefits of self-care training have been demonstrated.
Dynamics in the Neurotrauma Catchment Area of a German University Hospital during the COVID-19 Pandemic
Authors: Rupa Rosita , Vladimirov Tim , Pojskic Mirza , Nimsky Christopher , Voellger Benjamin
Published: July 2022

Objective: At the beginning of 2020, the COVID-19 pandemic enforced a rapid reallocation of healthcare resources. Our neurosurgical department is located in the German county of Marburg–Biedenkopf, about 80 km from the nearest major city. We were able to maintain our previously established open-door policy after the emergence of COVID-19. Here, we report on dynamics in the catchment area for neurotrauma patients at our department during the pandemic. Methods: 763 consecutive neurotrauma cases admitted to our department between 1 January 2018 and 31 December 2021 were analyzed retrospectively. Patients’ age, gender, origin, diagnoses, and outcomes were recorded. The number of patients hospitalized with a COVID-19 infection in Germany (PHCG) were retrieved from the Robert Koch Institute (RKI). We defined calendar weeks with >1000 PHCG as high COVID-19 caseload weeks (HCLW). Chi-square and Fisher’s exact served as statistical tests. Results: In 2020 and 2021, we observed a significantly increased number of neurotrauma patients who, with primary residence outside of our district, were admitted to our hospital compared to 2018 and 2019 (p < 0.001), while there were no significant differences in in-house mortality. During HCLW, a significantly increased number of neurotrauma patients with primary residence in the densely populated southwestern margin (SWM) of the contiguous part of our catchment area were referred to us compared to the time prior to the pandemic and between HCLW (p = 0.003). In neurotrauma patients admitted from the SWM during HCLW, there was no tendency towards higher in-house mortality. Conclusion: An open-door policy may moderate the risk of involuntarily triaging neurotrauma patients during a pandemic.
Patterns of Outpatient Service Satisfaction among Low-Income Adults in Rural China: A Latent Class Analysis
Authors: Lu Peiyi , Yang Chunyu , Yao Jun , Xian Mingxia , Shelley Mack
Published: July 2022

(1) Background: Low-income rural residents in China are disadvantaged due to their financial vulnerability and insufficient access to resources, and this situation demands more research effort. This study examined the pattern of outpatient service satisfaction and its determinants among low-income adults in rural China. (2) Methods: Rural low-income respondents who used outpatient services in their local healthcare facilities in Jiangsu, China evaluated the access, cost, environment, doctor–patient interaction, and other topics during their outpatient visit (N = 662). Latent class analysis was used to identify the groups characterized by various dimensions of outpatient satisfaction. Multinomial logistic regression explored the determinants of class membership. (3) Results: Three latent classes were identified: 28.70% had low satisfaction, unsatisfied with every dimension; 20.69% reported medium satisfaction that valued doctor–patient relationships; and 50.60% had high satisfaction but thought that costs were high. Both low and medium satisfaction were associated with a higher proportion of self-paid fees. (4) Conclusions: Healthcare costs were an important determinant of outpatient service satisfaction. Medical social workers are suggested to be included in the medical team to help patients identify financial assistance. Special aid programs may be developed to help relieve rural low-income patients’ medical cost-related burden.
What Causes Health Information Avoidance Behavior under Normalized COVID-19 Pandemic? A Research from Fuzzy Set Qualitative Comparative Analysis
Authors: Ding Qingxiu , Gu Yadi , Zhang Gongrang , Li Xingguo , Zhao Qin , Gu Dongxiao , Yang Xuejie , Wang Xiaoyu
Published: July 2022

Affected by the normalization of the COVID-19 pandemic, people’s lives are subject to many restrictions, and they are under enormous psychological and physical pressure. In this situation, health information may be a burden and cause of anxiety for people; thus, the refusal of health information occurs frequently. Health-information-avoidance behavior has produced potential impacts and harms on people’s lives. Based on more than 120,000 words of textual data obtained from semi-structured interviews, summarizing a case collection of 55 events, this paper explores the factors and how they combine to lead to avoidance of health information. First, the influencing factors are constructed according to the existing research, and then the fuzzy set qualitative comparative analysis (fsQCA) method is used to discover the configuration relationship of health-information-avoidance behavior. The results show that the occurrence of health-information avoidance is not the result of a single factor but the result of a configuration of health-information literacy, negative emotions, perceived information, health-information presentation, cross-platform distribution, and the network information environment. These findings provide inspiration for reducing the adverse consequences of avoiding health information and improving the construction of health-information service systems.
Response Characteristics of Electric Potential and Its Relationship with Dynamic Disaster during Mining Activities: A Case Study in Xuehu Coal Mine, China
Authors: Niu Yue , Li Zhonghui , Wang Enyuan , Shan Tiancheng , Wang Heng , Xu Shilong , Sun Wenyang , Wang Guanteng , Xue Xingzhuo , Liu Junqi
Published: July 2022

Across the world, coal resource is widely utilized in industrial production. During coal mining activities, dynamic disasters may be induced, such as coal and gas outbursts, or rock burst, resulting in serious accidents or disasters. Previous studies have shown that electric potential (EP) signals can be produced during the deformation and fracture process of coal and rock mass under load. The abnormal response characteristics of EP can reveal the damage evolution and failure feather of coal mass. In this paper, the response characteristics of EP signals are analyzed with high gas testing during mining activities within deep coal seams, and the relationship between the EP response and outburst disaster hazard is studied. The results show that: (1) Under the comprehensive action of mining stress and gas effect, the coal mass was damaged and fractured, which can produce abundant EP signals, while the temporal EP response characteristics can reflect the loading state and damage evolution process inside the coal seam. (2) When coal cannon and a sudden increase of gas concentration occurred in the coal mass, the EP signal was at a high level and fluctuated violently. This can be regarded as precursory information for an outburst risk, which was verified by monitoring the results of mining stress and electromagnetic radiation (EMR). (3) Based on the unilateral inversion imaging method, EP spatial distribution law was studied and abnormal zones with high-value were identified. The zone is close to, or coincident with, the high value interval of EMR intensity and count indexes, which revealed the distribution characteristics of coal damage localization. Hence, EP monitoring results can forecast precursor information of outburst hazards temporally, and identify local zones with outburst hazard spatially. This study provides a new idea and application basis for using the EP method to monitor and prevent coal and rock dynamic disaster hazards in the field.
Methodologies for Monitoring the Digital Marketing of Foods and Beverages Aimed at Infants, Children, and Adolescents (ICA): A Scoping Review
Authors: Lara-Mejía Vania , Franco-Lares Bianca , Lozada-Tequeanes Ana Lilia , Villanueva-Vázquez Casandra , Hernández-Cordero Sonia
Published: July 2022

While television has been the most widely used medium for food and beverage marketing, companies are shifting in favor of digital media. The ubiquitous digital marketing of breast-milk substitutes (BMS) and foods and beverages high in saturated fat, salt, and/or free sugars (FBHFSS) has been considered a powerful environmental determinant of inadequate dietary practices during infancy, childhood, and adolescence. The scoping review’s aim was to systematically identify and map the types of methodologies available to monitor the digital marketing of foods and beverages targeting infants, children, and adolescents (ICA) worldwide. Research evidence published from 2011 to October 2021 was examined using search strategies including multiple databases and citation tracking. A total of 420 sources were evaluated, and 28 studies from 81 countries meeting the inclusion criteria were retained. Most of the studies (n = 24) documenting methodologies to monitor inappropriate digital marketing were published since 2015 and were primarily aimed at identifying the promotional techniques and nutritional content of FBHFSS targeting adolescents (n = 13). It is paramount to develop a feasible and scalable monitoring system to develop effective policies to protect parents and ICA from BMS and FBHSFF digital marketing.
Mental Health during the Early Stage of the COVID-19 Pandemic: A Hong Kong Study
Authors: Cheung Pik-Kwan , Wu Joseph , Chui Wing-Hong
Published: July 2022

This study addressed the impact on mental health and wellbeing in relation to views of the self, the world, and the future during the early stage of the global novel coronavirus (COVID-19) pandemic outbreak. An online survey battery included the 21-item Depression Anxiety and Stress Scale (DASS-21), Subjective Happiness Scale, Self-Compassion Scale, Adult Hope Scale, and two specifically-written items measuring the valence quality and quantity of the impact of the pandemic. A total of 345 Hong Kong residents (54% females) responded; 17.1%, 24.7%, and 19.7% reported elevated levels of depression, anxiety, and stress, respectively. The prevalence of these issues was lower in this Hong Kong sample than reported in other COVID-19 studies, possibly due to the past experience of the severe acute respiratory syndrome (SARS) outbreak in Hong Kong in promoting the voluntary wearing of masks in public places and introducing social distancing measures during the early first wave of the pandemic. Correlational analyses showed associations between positive views about the self (higher self-compassion), the world (higher positive valence), and the future (more hope) and better mental health and psychological wellbeing (fewer depression, anxiety, and stress symptoms; more happiness). Regression analyses indicated a differential predicting power of the three views on the four selected mental health and psychological wellbeing indicators. Intervention programs to alleviate distress and/or promote better wellbeing should be matched to the specific problems encountered by the sufferers.
Injury Characteristics among Young Adults during and Immediately after the COVID-19 Lockdown
Authors: Quintana-Cepedal Marcos , Rodríguez Miguel Ángel , Crespo Irene , Terrados Nicolás , Sánchez Martínez Beatriz , del Valle Miguel , Olmedillas Hugo
Published: July 2022

The lockdown due to the COVID-19 pandemic inherently changed people’s lifestyles. Forty-eight days of isolation led to worsening physical fitness in addition to the development of other unhealthy habits. The aim of this study was to describe sport-related injuries in the active general population. Physical therapy centres and sports medicine clinics were contacted via e-mail, seeking patients who had sustained an injury during or immediately (up to two weeks) after the lockdown. Patients who agreed to participate completed an online survey that followed the International Olympic Committee Statement. The questionnaire focused on physical exercise habits, type of injury, location and tissue affected. A total of 51 females and 67 males (30.5, SD = 8.8 years) participated in the study. Eighty percent of the participants performed aerobic training sessions, while the rest dedicated their workouts to strength training. Two in every three injuries were located in the lower limbs, and 80% affected the musculoskeletal tissue. Of all the injuries recorded, 67% occurred during the first week after lockdown. The number of aerobic exercise sessions was positively correlated with lower limb injuries (χ2 = 17.12, p < 0.05). Exercise habits should be considered when planning to return to a sport after a period of confinement to avoid injury.
Analysis of Scientometric Indicators in Publications Associated with Healthy Aging in the World, Period 2011–2020
Authors: Rojas-Montesino Eric , Méndez Diego , Espinosa-Parrilla Yolanda , Fuentes Eduardo , Palomo Iván
Published: July 2022

Today, the world population is aging at a fast rate. This scenario of the accelerated aging of human populations entails increased concern for healthy aging that is associated with a rise in scientific production related to the topic. In this study, the Scopus database from Elsevier was used, with a final search carried out on 5 January 2022, and various bibliometric indicators were obtained from SciVal. The study was fundamentally intended to characterize, determine trends, and understand the evolution and current state of research on the concept of “healthy aging” in the last decade. We found that there has been proportionally greater and more accelerated growth in the subject with respect to the general productivity of the world and that countries with high life expectancies tend to have made more effort to investigate this topic. The “hottest” research areas were found to be related to the cognitive aspect and the biological mechanisms involved in aging.
Surveillance of Drinking Water Quality Worldwide: Scoping Review Protocol
Authors: Lopes Rayssa Horacio , Silva Cícera Renata Diniz Vieira , Salvador Pétala Tuani Cândido de Oliveira , Silva Ísis de Siqueira , Heller Léo , Uchôa Severina Alice da Costa
Published: July 2022

Universal access to clean and safe drinking water is essential for life maintenance since exposure to poor quality water is harmful to health. Drinking water quality is part of public health actions and, together with sanitation, a human right essential for life and a sustainable development goal. Moreover, an independent surveillance system conducted by the Ministry of Health or government agencies is needed for the safety of drinking water quality. We propose a scoping review protocol to identify and map worldwide surveillance actions and initiatives of drinking water quality implemented by government agencies or public health services. This scoping review protocol is based on the Joanna Briggs Institute manual and guided by the PRISMA-ScR. Articles, theses, dissertations, and official documents consulted in the following databases will be included: Medline/PubMed, Scopus, LILACS, Web of Science, Embase, Engineering Village, and gray literature. No date limit or language will be determined. The authors will develop a worksheet for data extraction. Quantitative (simple descriptive statistics) and qualitative data (thematic analysis) will be analyzed. The final scoping review will present the main findings, impacts, challenges, limitations, and possible research gaps related to surveillance of drinking water quality on population health.
The Implications of Family Members’ Absence from Hospital Visits during the COVID-19 Pandemic: Nurses’ Perceptions
Authors: Correia Tânia Sofia Pereira , Martins Maria Manuela F. P. S. , Barroso Fernando F. , Pinho Lara G. , Fonseca César , Valentim Olga , Lopes Manuel
Published: July 2022

Background: In response to the COVID-19 pandemic, several measures were taken to prevent the transmission of infection in the hospital environment, including the restriction of visits. Little is known about the consequences of these directives, but it is expected that they will have various implications. Thus, this study aimed to understand the consequences of measures to restrict visits to hospitalized individuals. Methods: A qualitative interpretive study was conducted through semistructured interviews with 10 nurses chosen by convenience. Content analysis was performed using Atlas.ti software, version 22 (Berlin, Germany). Results: Twenty-two categories and eight subcategories were identified and grouped according to their scope: implications for the patient, implications for the family, and implications for care practice. Conclusions: The identified categories of implications of restricting hospital visits (implications for patients, relatives, and care practices) are incomparably more negative than positive and have a strong potential to cause safety events in the short to long term, also jeopardizing the quality of care. There is the risk of stagnation and even setback due to this removal of families from the hospital environment, not only in terms of safety and quality of care but also with regard to person- and family-centered care.
“Intervention Program Based on Self”: A Proposal for Improving the Addiction Prevention Program “Unplugged” through Self-Concept
Authors: Bourduge Cédrine , Brousse Georges , Morel Florence , Pereira Bruno , Lambert Céline , Izaute Marie , Teissedre Frédérique
Published: July 2022

The “Intervention Program based on Self” (IPSELF) project was created to address the gap between the acquisition of life skills during prevention programs and their application with a session for developing one’s self-concept included in the European program “Unplugged”. The present study evaluated its effectiveness. A total of 157 middle school students (94 girls, 63 boys, MAGE= 12.89, SD = 0.45) from three schools in France participated in this study. The participants attended one of two programs (Unplugged/IPSELF). The effectiveness of the IPSELF add-on session was measured with the Self-Concept Clarity Scale, and the differences between the two programs was measured with the prototype willingness model. Adolescents in IPSELF rated the typical nonsmoker and cannabis nonsmoker more favorably, and the typical drinker less favorably. They felt more different from the typical smoker and drinker after participation in IPSELF. More alcohol experimenters were observed in Unplugged. The knowledge gained in IPSELF appeared to help adolescents more than that gained in Unplugged to change their smoking behavior. Furthermore, IPSELF had a more beneficial effect for girls, who felt that they had gained more control over their alcohol and cannabis use than boys, whereas Unplugged had a more positive effect on boys, who gained better control over their consumption. Moreover, the girls felt that they had gained more knowledge about the substances discussed in IPSELF than in Unplugged. We therefore recommend the use of IPSELF especially with female audiences.
Association between Health Literacy and Prevalence of Obesity, Arterial Hypertension, and Diabetes Mellitus
Authors: Lovrić Božica , Placento Harolt , Farčić Nikolina , Lipič Baligač Metka , Mikšić Štefica , Mamić Marin , Jovanović Tihomir , Vidić Hrvoje , Karabatić Sandra , Cviljević Sabina , Zibar Lada , Vukoja Ivan , Barać Ivana
Published: July 2022

Background: Health literacy (HL) is linked to many health outcomes, including self-management of chronic diseases. The aim of this study was to assess the association of health literacy with the prevalence of obesity, arterial hypertension (AH), and type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, single-center study included 500 patients (42.2% male and 57.8% females; median age, 63 years (interquartile range, 42–73)) hospitalized at General County Hospital in Požega, Croatia, between July and October 2020. The Short Assessment of Health Literacy for Croatian Adults (SAHLCA-50) questionnaire was used. Descriptive statistics (median with interquartile range (IQR), frequency, and percentages) and binary logistic regression were utilized. Results: Patients with AH had an inadequate level of health literacy as compared to those without AH (32 vs. 40 points; Mann–Whitney U test, p < 0.001). Patients with T2DM scored 31 points versus 39 points in patients without T2DM (Mann–Whitney U test, p < 0.001). Patients suffering from both AH and T2DM scored 31 points versus 33 points in those with either AH or T2DM and 41 points in patients without AH and T2DM (Kruskal–Wallis test, p < 0.001). There were no statistically significant differences in SAHLCA-50 scores according to the patient body mass index. Conclusions: An inadequate level of health literacy is significantly associated with AH and T2DM but not with obesity. Male gender, low level of education, rural place of residence, retirement, and older age are significant predictors of inadequate health literacy.
Morphological Changes in the Oral Mucous Membrane in Viral Hepatitis C Patients: A Cross-Sectional Study
Authors: Azatyan Vahe , Yessayan Lazar , Sargsyan Aelita , Khachatryan Anna , Ghevondyan Tigran , Shmavonyan Melanya , Melik-Andreasyan Gayane , Porksheyan Kristina , Manrikyan Mikael
Published: July 2022

Background: The objective was to reveal the most typical changes in oral mucosa in HCV patients and compare them with those in HCV negative patients. Methods: The study involved 96 HCV patients and 100 patients without HCV who applied to a dental clinic. The content of cytokines IL-2, IL-4, IL-10 and ɤ-INF in the oral fluid was determined by ELISA. Buccal mucosa and gums biopsies passed histological examination. An immunohistochemical study of mucous membrane biopsies was performed using monoclonal mouse antibodies to CD3+ and CD20+. Results: The HCV patients group included 96 (63.5% males), and the non-HCV group included 100 subjects (62.0% males) with lesions of the oral mucous membrane. The lesions of lips and oral mucosa were more frequent in HCV than in the non-HCV group—e.g., erosion (13.5% vs. 1%), cracks in the mouth corners (42.7% vs. 0%), changes in the oral mucosa surface (89.6% vs. 3.0%), hemorrhages (78.1% vs. 0%), etc. The pro-inflammatory IL-2 level was higher and anti-inflammatory IL-4 level was lower in HCV patients compared with those in the non-HCV group. Conclusions: Morphological changes developed in the microvasculature both worsen the tissue trophism and accelerate the healing with differentiation into coarse-fibrous connective tissue. Immunohistochemical findings indicated a decrease in local humoral immune response.
Accelerometer-Measured Physical Activity and Sedentary Behavior of Adults with Prader-Willi Syndrome Attending and Not Attending a Small-Scale Community Workshop
Authors: Wu Ming-Ju , Tsai Li-Ping , Lai Ting-Fu , Cho Jeong Su , Liao Yung
Published: July 2022

This cross-sectional study aimed to compare the accelerometer-assessed physical activity (PA) and sedentary behavior (SB) of adults with Prader-Willi syndrome (PWS) attending or not attending a small-scale community workshop (SSCW). A total of 18 adults with PWS were recruited in this study. Of these participants, 10 regularly attended an SSCW and 8 did not. All of the participants were asked to wear accelerometers for eight continuous days for measuring their PA and SB. The independent sample t-test was used. The results showed that the adults with PWS who attended the SSCW engaged in more moderate-to-vigorous PA (MVPA) and daily steps than those who did not. By stratifying between daytime/nighttime on weekdays, we found the participants who attended the SSCW had higher total PA, MVPA, daily steps, as well as lower total sedentary time, during the daytime on weekdays than those who did not. Policies or programs promoting PA and reducing SB among adults with PWS should thus consider providing structured programs or courses in a community center.
1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line
Authors: de Sousa Portilho Adrhyann Jullyanne , da Silva Emerson Lucena , Bezerra Emanuel Cintra Austregésilo , Moraes Rego Gomes Carinne Borges de Souza , Ferreira Vitor , de Moraes Maria Elisabete Amaral , da Rocha David Rodrigues , Burbano Rommel Mário Rodriguez , Moreira-Nunes Caroline Aquino , Montenegro Raquel Carvalho
Published: July 2022

The multidrug resistance (MDR) phenotype is one of the major obstacles in the treatment of chronic myeloid leukemia (CML) in advantage stages such as blast crisis. In this scenario, more patients develop resistance mechanisms during the course of the disease, making tyrosine kinase inhibitors (TKIs) target therapies ineffective. Therefore, the aim of the study was to examine the pharmacological role of CNN1, a para-naphthoquinone, in a leukemia multidrug resistant cell line. First, the in vitro cytotoxic activity of Imatinib Mesylate (IM) in K-562 and FEPS cell lines was evaluated. Subsequently, membrane integrity and mitochondrial membrane potential assays were performed to assess the cytotoxic effects of CNN1 in K-562 and FEPS cell lines, followed by cell cycle, alkaline comet assay and annexin V-Alexa Fluor® 488/propidium iodide assays (Annexin/PI) using flow cytometry. RT-qPCR was used to evaluate the H2AFX gene expression. The results demonstrate that CNN1 was able to induce apoptosis, cell membrane rupture and mitochondrial membrane depolarization in leukemia cell lines. In addition, CNN1 also induced genotoxic effects and caused DNA fragmentation, cell cycle arrest at the G2/M phase in leukemia cells. No genotoxicity was observed on peripheral blood mononuclear cells (PBMC). Additionally, CNN1 increased mRNA levels of H2AFX. Therefore, CNN1 presented anticancer properties against leukemia multidrug resistant cell line being a potential anticancer agent for the treatment of resistant CML.
Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells
Authors: Silva Amélia M. , Martins-Gomes Carlos , Ferreira Sandrine S. , Souto Eliana B. , Andreani Tatiana
Published: July 2022

In this work, three pesticides of different physicochemical properties: glyphosate (GLY, herbicide), imidacloprid (IMD, insecticide), and imazalil (IMZ, fungicide), were selected to assess their cytotoxicity against Caco-2 and HepG2 cells. Cell viability was assessed by the Alamar Blue assay, after 24 and 48 h exposure to different concentrations, and IC50 values were calculated. The mechanisms underlying toxicity, namely cellular reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation, loss of mitochondrial membrane potential (MMP), and apoptosis/necrosis induction were assessed by flow cytometry. Cytotoxic profiles were further correlated with the molecular physicochemical parameters of pesticides, namely: water solubility, partition coefficient in an n-octanol/water (Log Pow) system, topological polar surface area (TPSA), the number of hydrogen-bonds (donor/acceptor), and rotatable bonds. In vitro outputs resulted in the following toxicity level: IMZ (Caco-2: IC50 = 253.5 ± 3.37 μM, and HepG2: IC50 = 94 ± 12 μM) > IMD (Caco-2: IC50 > 1 mM and HepG2: IC50 = 624 ± 24 μM) > GLY (IC50 >>1 mM, both cell lines), after 24 h treatment, being toxicity time-dependent (lower IC50 values at 48 h). Toxicity is explained by oxidative stress, as IMZ induced a higher intracellular ROS increase and lipid peroxidation, followed by IMD, while GLY did not change these markers. However, the three pesticides induced loss of MMP in HepG2 cells while in Caco-2 cells only IMZ produced significant MMP loss. Increased ROS and loss of MMP promoted apoptosis in Caco-2 cells subjected to IMZ, and in HepG2 cells exposed to IMD and IMZ, as assessed by Annexin-V/PI. The toxicity profile of pesticides is directly correlated with their Log Pow, as affinity for the lipophilic environment favours interaction with cell membranes governs, and is inversely correlated with their TPSA; however, membrane permeation is favoured by lower TPSA. IMZ presents the best molecular properties for membrane interaction and cell permeation, i.e., higher Log Pow, lower TPSA and lower hydrogen-bond (H-bond) donor/acceptor correlating with its higher toxicity. In conclusion, molecular physicochemical factors such as Log Pow, TPSA, and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus they are key factors to potentially predict the toxicity of other compounds.
Assessment of the Antioxidant Activity of Catechin in Nutraceuticals: Comparison between a Newly Developed Electrochemical Method and Spectrophotometric Methods
Authors: Munteanu Irina Georgiana , Apetrei Constantin
Published: July 2022

The analysis of antioxidants in different foodstuffs has become an active area of research, which has led to many recently developed antioxidant assays. Many antioxidants exhibit inherent electroactivity, and, therefore, the use of electrochemical methods could be a viable approach for evaluating the overall antioxidant activity of a matrix of nutraceuticals without the need for adding reactive species. Green tea is believed to be a healthy beverage due to a number of therapeutic benefits. Catechin, one of its constituents, is an important antioxidant and possesses free radical scavenging abilities. The present paper describes the electrochemical properties of three screen-printed electrodes (SPEs), the first one based on carbon nanotubes (CNTs), the second one based on gold nanoparticles (GNPs) and the third one based on carbon nanotubes and gold nanoparticles (CNTs-GNPs). All three electrodes were modified with the laccase (Lac) enzyme, using glutaraldehyde as a cross-linking agent between the amino groups on the laccase and aldehyde groups of the reticulation agent. As this enzyme is a thermostable catalyst, the performance of the biosensors has been greatly improved. Electro-oxidative properties of catechin were investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV), and these demonstrated that the association of CNTs with GNPs significantly improved the sensitivity and selectivity of the biosensor. The corresponding limit of detection (LOD) was estimated to be 5.6 × 10−8 M catechin at the CNT-Lac/SPE, 1.3 × 10−7 M at the GNP-Lac/SPE and 4.9 × 10−8 M at the CNT-GNP-Lac/SPE. The biosensors were subjected to nutraceutical formulations containing green tea in order to study their catechin content, using CNT-GNP-Lac/SPE, through DPV. Using a paired t-test, the catechin content estimated was in agreement with the manufacturer’s specification. In addition, the relationship between the CNT-GNP-Lac/SPE response at a specific potential and the antioxidant activity of nutraceuticals, as determined by conventional spectrophotometric methods (DPPH, galvinoxyl and ABTS), is discussed in the context of developing a fast biosensor for the relative antioxidant activity quantification.
An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds
Authors: Ebenezer Oluwakemi , Jordaan Maryam Amra. , Carena Gea , Bono Tommaso , Shapi Michael , Tuszynski Jack A.
Published: July 2022

Heterocyclic compounds are a class of compounds of natural origin with favorable properties and hence have major pharmaceutical significance. They have an exceptional adroitness favoring their use as diverse smart biomimetics, in addition to possessing an active pharmacophore in a complex structure. This has made them an indispensable motif in the drug discovery field. Heterocyclic compounds are usually classified according to the ring size, type, and the number of heteroatoms present in the ring. Among different heterocyclic ring systems, nitrogen heterocyclic compounds are more abundant in nature. They also have considerable pharmacological significance. This review highlights recent pioneering studies in the biological assessment of nitrogen-containing compounds, namely: triazoles, tetrazoles, imidazole/benzimidazoles, pyrimidines, and quinolines. It explores publications between April 2020 and February 2022 and will benefit researchers in medicinal chemistry and pharmacology. The present work is organized based on the size of the heterocyclic ring.
Glycidyl Methacrylate-Based Copolymers as Healing Agents of Waterborne Polyurethanes
Authors: Tzoumani Ioanna , Soto Beobide Amaia , Iatridi Zacharoula , Voyiatzis George A. , Bokias Georgios , Kallitsis Joannis K.
Published: July 2022

Self-healing materials and self-healing mechanisms are two topics that have attracted huge scientific interest in recent decades. Macromolecular chemistry can provide appropriately tailored functional polymers with desired healing properties. Herein, we report the incorporation of glycidyl methacrylate-based (GMA) copolymers in waterborne polyurethanes (WPUs) and the study of their potential healing ability. Two types of copolymers were synthesized, namely the hydrophobic P(BA-co-GMAy) copolymers of GMA with n-butyl acrylate (BA) and the amphiphilic copolymers P(PEGMA-co-GMAy) of GMA with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomer. We demonstrate that the blending of these types of copolymers with two WPUs leads to homogenous composites. While the addition of P(BA-co-GMAy) in the WPUs leads to amorphous materials, the addition of P(PEGMA-co-GMAy) copolymers leads to hybrid composite systems varying from amorphous to semi-crystalline, depending on copolymer or blend composition. The healing efficiency of these copolymers was explored upon application of two external triggers (addition of water or heating). Promising healing results were exhibited by the final composites when water was used as a healing trigger.
Structure-Function Relationships in Temperature Effects on Bacterial Luciferases: Nothing Is Perfect
Authors: Deeva Anna A. , Lisitsa Albert E. , Sukovatyi Lev A. , Melnik Tatiana N. , Kratasyuk Valentina A. , Nemtseva Elena V.
Published: July 2022

The evaluation of temperature effects on the structure and function of enzymes is necessary to understand the mechanisms underlying their adaptation to a constantly changing environment. In the current study, we investigated the influence of temperature variation on the activity, structural dynamics, thermal inactivation and denaturation of Photobacterium leiognathi and Vibrio harveyi luciferases belonging to different subfamilies, as well as the role of sucrose in maintaining the enzymes functioning and stability. We used the stopped-flow technique, differential scanning calorimetry and molecular dynamics to study the activity, inactivation rate, denaturation and structural features of the enzymes under various temperatures. It was found that P. leiognathi luciferase resembles the properties of cold-adapted enzymes with high activity in a narrow temperature range and slightly lower thermal stability than V. harveyi luciferase, which is less active, but more thermostable. Differences in activity at the studied temperatures can be associated with the peculiarities of the mobile loop conformational changes. The presence of sucrose does not provide an advantage in activity but increases the stability of the enzymes. Differential scanning calorimetry experiments showed that luciferases probably follow different denaturation schemes.
Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19
Authors: Loh Doris , Reiter Russel J.
Published: July 2022

The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of “viral factories” by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.
High-Density Lipoproteins: A Role in Inflammation in COPD
Authors: Kotlyarov Stanislav
Published: July 2022

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high rates of disability and mortality. COPD is characterized by chronic inflammation in the bronchi as well as systemic inflammation, which contributes significantly to the clinically heterogeneous course of the disease. Lipid metabolism disorders are common in COPD, being a part of its pathogenesis. High-density lipoproteins (HDLs) are not only involved in lipid metabolism, but are also part of the organism’s immune and antioxidant defense. In addition, HDL is a versatile transport system for endogenous regulatory agents and is also involved in the removal of exogenous substances such as lipopolysaccharide. These functions, as well as information about lipoprotein metabolism disorders in COPD, allow a broader assessment of their role in the pathogenesis of heterogeneous and comorbid course of the disease.
Photocatalytic Degradation of Some Typical Antibiotics: Recent Advances and Future Outlooks
Authors: Bai Xue , Chen Wanyu , Wang Bao , Sun Tianxiao , Wu Bin , Wang Yuheng
Published: July 2022

The existence of antibiotics in the environment can trigger a number of issues by fostering the widespread development of antimicrobial resistance. Currently, the most popular techniques for removing antibiotic pollutants from water include physical adsorption, flocculation, and chemical oxidation, however, these processes usually leave a significant quantity of chemical reagents and polymer electrolytes in the water, which can lead to difficulty post-treating unmanageable deposits. Furthermore, though cost-effectiveness, efficiency, reaction conditions, and nontoxicity during the degradation of antibiotics are hurdles to overcome, a variety of photocatalysts can be used to degrade pollutant residuals, allowing for a number of potential solutions to these issues. Thus, the urgent need for effective and rapid processes for photocatalytic degradation leads to an increased interest in finding more sustainable catalysts for antibiotic degradation. In this review, we provide an overview of the removal of pharmaceutical antibiotics through photocatalysis, and detail recent progress using different nanostructure-based photocatalysts. We also review the possible sources of antibiotic pollutants released through the ecological chain and the consequences and damages caused by antibiotics in wastewater on the environment and human health. The fundamental dynamic processes of nanomaterials and the degradation mechanisms of antibiotics are then discussed, and recent studies regarding different photocatalytic materials for the degradation of some typical and commonly used antibiotics are comprehensively summarized. Finally, major challenges and future opportunities for the photocatalytic degradation of commonly used antibiotics are highlighted.
HPV Integration Site Mapping: A Rapid Method of Viral Integration Site (VIS) Analysis and Visualization Using Automated Workflows in CLC Microbial Genomics
Authors: Shen-Gunther Jane , Cai Hong , Wang Yufeng
Published: July 2022

Human papillomavirus (HPV) integration within the host genome may contribute to carcinogenesis through various disruptive mechanisms. With next-generation sequencing (NGS), identification of viral and host genomic breakpoints and chimeric sequences are now possible. However, a simple, streamlined bioinformatics workflow has been non-existent until recently. Here, we tested two new, automated workflows in CLC Microbial Genomics, i.e., Viral Hybrid Capture (VHC) Data Analysis and Viral Integration Site (VIS) Identification for software performance and efficiency. The workflows embedded with HPV and human reference genomes were used to analyze a publicly available NGS dataset derived from pre- and cancerous HPV+ cervical cytology of 21 Gabonese women. The VHC and VIS workflow median runtimes were 19 and 7 min per sample, respectively. The VIS dynamic graphical outputs included read mappings, virus-host genomic breakpoints, and virus-host integration circular plots. Key findings, including disrupted and nearby genes, were summarized in an auto-generated report. Overall, the VHC and VIS workflows proved to be a rapid and accurate means of localizing viral-host integration site(s) and identifying disrupted and neighboring human genes. Applying HPV VIS-mapping to pre- or invasive tumors will advance our understanding of viral oncogenesis and facilitate the discovery of prognostic biomarkers and therapeutic targets.
Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
Authors: Montes-Mojarro Ivonne A. , Hassas Saki , Staehle Sina , Sander Philip , Harland Niklas , Serna-Higuita Lina Maria , Bonzheim Irina , Bösmüller Hans , Stenzl Arnulf , Fend Falko
Published: July 2022

Diagnosis and grading of non-invasive papillary urothelial tumors according to the current WHO classification poses some challenges for pathologists. The diagnostic reproducibility of separating low-grade and high-grade lesions is low, which impacts their clinical management. Whereas papillary urothelial neoplasms with low malignant potential (PUN-LMP) and low-grade papillary non-invasive carcinoma (LG-PUC) are comparable and show frequent local recurrence but rarely metastasize, high-grade papillary non-invasive carcinoma (HG-PUC) has a poor prognosis. The main objective of this work is to develop a multiparametric classification to unambiguously distinguish low-grade and high-grade tumors, considering immunohistochemical stains for p53, FGFR3, CK20, MIB-1, p16, p21 and p-HH3, and pathogenic mutations in TP53, FGFR3, TP53, ERCC2, PIK3CA, PTEN and STAG2. We reviewed and analyzed the clinical and histological data of 45 patients with a consensus diagnosis of PUN-LMP (n = 8), non-invasive LG-PUC (n = 23), and HG-PUC (n = 14). The proliferation index and mitotic count assessed with MIB-1 and P-HH3 staining, respectively correlated with grading and clinical behavior. Targeted sequencing confirmed frequent FGFR3 mutations in non-invasive papillary tumors and identified mutations in TP53 as high-risk. Cluster analysis of the different immunohistochemical and molecular parameters allowed a clear separation in two different clusters: cluster 1 corresponding to PUN-LMP and LG-PUC (low MIB-1 and mitotic count/FGFR3 and STAG2 mutations) and cluster 2, HG-PUC (high MIB-1 and mitosis count/CK20 +++ expression, FGFR3 WT and TP53 mutation). Further analysis is required to validate and analyze the reproducibility of these clusters and their biological and clinical implication.
Isolated Variable Domains of an Antibody Can Assemble on Blood Coagulation Factor VIII into a Functional Fv-like Complex
Authors: Shestopal Svetlana A. , Parunov Leonid A. , Olivares Philip , Chun Haarin , Ovanesov Mikhail V. , Pettersson John R. , Sarafanov Andrey G.
Published: July 2022

Single-chain variable fragments (scFv) are antigen-recognizing variable fragments of antibodies (FV) where both subunits (VL and VH) are connected via an artificial linker. One particular scFv, iKM33, directed against blood coagulation factor VIII (FVIII) was shown to inhibit major FVIII functions and is useful in FVIII research. We aimed to investigate the properties of iKM33 enabled with protease-dependent disintegration. Three variants of iKM33 bearing thrombin cleavage sites within the linker were expressed using a baculovirus system and purified by two-step chromatography. All proteins retained strong binding to FVIII by surface plasmon resonance, and upon thrombin cleavage, dissociated into VL and VH as shown by size-exclusion chromatography. However, in FVIII activity and low-density lipoprotein receptor-related protein 1 binding assays, the thrombin-cleaved iKM33 variants were still inhibitory. In a pull-down assay using an FVIII-affinity sorbent, the isolated VH, a mixture of VL and VH, and intact iKM33 were carried over via FVIII analyzed by electrophoresis. We concluded that the isolated VL and VH assembled into scFv-like heterodimer on FVIII, and the isolated VH alone also bound FVIII. We discuss the potential use of both protease-cleavable scFvs and isolated Fv subunits retaining high affinity to the antigens in various practical applications such as therapeutics, diagnostics, and research.