bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotating Night Shift Work, Exposure to Light at Night, and Glomerular Filtration Rate: Baseline Results from a Chinese Occupational Cohort
Authors: Zhang Shengkui , Wang Yongbin , Zhu Ying , Li Xiaoming , Song Yang , Yuan Juxiang
Published: December 2020

The misalignment between the circadian clock and behavioral cycles has been implicated in pathogenesis of many diseases. The main purpose of this study is to examine the association between rotating night shift work, exposure to light at night, and glomerular filtration rate among steelworkers in north China. A total of 6869 steelworkers, aged 22 to 60 years, were included in this study. Multivariable logistic regression was used to examine the association between night shift work, the brightness of bedroom ambient light at night (LAN), and estimated glomerular filtration rate (eGFR), with adjustment for potential confounders. Mediation analysis was performed to examine the mediation effect of potential mediators on the association of duration of night shifts and eGFR. Long duration of night shift work (≥29 years) had elevated odds of decreased eGFR (≤89 mL/min/1.73 m2) (odds ratio (OR), 1.37, 95% confidence interval (CI) 1.09–1.73) compared with day work after adjustment for potential confounders. The association between duration of night shifts and eGFR (continuous) was partially modified by diastolic blood pressure (average causal mediation effect (ACME), –0.077, 95% CI –0.134 to −0.030, p < 0.001). No significant associations were observed among the different brightness of bedroom ambient light levels: middle level (OR, 0.90, 95% CI 0.77–1.05), lightest level (OR, 0.94, 95% CI 0.75–1.18), and decreased eGFR compared with the darkest level. Long-term night-shift work, rather than the brightness of bedroom ambient LAN, is associated with early stage of renal dysfunction in steelworkers, and blood pressure may mediate the relationship between night shift work and decreased eGFR.
Acute Effects of Brief Mindfulness Intervention Coupled with Carbohydrate Ingestion to Re-Energize Soccer Players: A Randomized Crossover Trial
Authors: Zhu Yuxin , Sun Fenghua , Li Chunxiao , Chow Daniel Hung Kay
Published: December 2020

Background: This field experiment investigated the acute effects of brief mindfulness-based intervention (MBI) coupled with carbohydrate (CHO) intake on players’ recovery from half-time break in a simulated soccer competition. Methods: In a single-blinded randomized crossover experiment, 14 male players received 3 treatments (Control: non-carbohydrate solution + travelling introduction audio; CHO: CHO–electrolyte solution + travelling introduction audio; and CHO_M: CHO–electrolyte solution + MBI) during simulated half-time breaks. Vertical jump, sprint performance, mindfulness level, rate of perceived exertion, muscle pain, mental fatigue, blood glucose, and lactate were measured immediately before, during, and after the exercise. Results: (1) MBI significantly increased participants’ mindfulness level (Control vs. CHO_M, p < 0.01; CHO vs. CHO_M, p < 0.01) and decreased mental fatigue for CHO_M condition (pre vs. post, p < 0.01); (2) participants in the CHO_M condition performed better in the repeated sprint tests than in the Control and CHO condition (Control vs. CHO_M, p = 0.02; CHO vs. CHO_M, p = 0.02). Conclusion: Findings of this study provide preliminary evidence of the positive effect of MBI coupled with CHO ingestion on athletes’ recovery from fatigue in the early stage of the second half of a game.
Anxiety, Depression and Quality of Life in Older Adults: Trajectories of Influence across Age
Authors: Ribeiro Oscar , Teixeira Laetitia , Araújo Lia , Rodríguez-Blázquez Carmen , Calderón-Larrañaga Amaia , Forjaz Maria João
Published: December 2020

This study focuses on the influence of anxiety and depression on individual trajectories of quality of life in old age through a longitudinal approach. A representative sample of adults aged 50+ living in Portugal and participating in wave 4 (W4) and wave 6 (W6) of the Survey of Health, Ageing and Retirement in Europe (SHARE) project was considered. Participants, 1765 at baseline (W4) and 1201 at follow up (W6), were asked about their quality of life (CASP-12) and emotional status (Euro-D scale; five items from the Beck Anxiety Inventory). Linear Mixed Effects models were performed to identify factors associated with changes in quality of life across age. Increasing age was found to have a significant negative effect on quality of life. Lower education and higher levels of depression and anxiety at baseline were also associated with worse quality of life; 42.1% of the variation of CASP-12 across age was explained by fixed and random effects, being depression followed by anxiety as the factors that presented with the highest relative importance. Both depression and anxiety play an important role in quality of life in older adults and must be acknowledged as important intervention domains to foster healthy and active aging.
Early Phase Management of the SARS-CoV-2 Pandemic in the Geographic Area of the Veneto Region, in One of the World’s Oldest Populations
Authors: Camerotto Alessandro , Sartorio Andrea , Mazzetto Anna , Gusella Milena , Luppi Ornella , Lucianò Domenica , Sofritti Olga , Pelati Cristiano , Munno Emilia , Tessari Andrea , Bedendo Simone , Bellè Margherita , Fenzi Federica , Formaglio Andrea , Boschini Annalisa , Busson Alberto , Spigolon Elisabetta , De Pieri Paolo , Casson Paola , Contato Edgardo , Compostella Antonio
Published: December 2020

The first cases of Coronavirus disease-2019 (COVID-19) were reported on 21 February in the small town of Vo’ near Padua in the Veneto region of Italy. This event led to 19,286 infected people in the region by 30 June 2020 (39.30 cases/10,000 inhabitants). Meanwhile, Rovigo Local Health Unit n. 5 (ULSS 5), bordering areas with high epidemic rates and having one of the world’s oldest populations, registered the lowest infection rates in the region (19.03 cases/10,000 inhabitants). The aim of this study was to describe timing and event management by ULSS 5 in preventing the propagation of infection within the timeframe spanning from 21 February to 30 June. Our analysis considered age, genetic clusters, sex, orography, the population density, pollution, and economic activities linked to the pandemic, according to the literature. The ULSS 5 Health Director General’s quick decision-making in the realm of public health, territorial assistance, and retirement homes were key to taking the right actions at the right time. Indeed, the number of isolated cases in the Veneto region was the highest among all the Italian regions at the beginning of the epidemic. Moreover, the implementation of molecular diagnostic tools, which were initially absent, enabled health care experts to make quick diagnoses. Quick decision-making, timely actions, and encouraging results were achieved thanks to a solid chain of command, despite a somewhat unclear legislative environment. In conclusion, we believe that the containment of the epidemic depends on the time factor, coupled with a strong sense of awareness and discretion in the Health Director General’s decision-making. Moreover, real-time communication with operating units and institutions goes hand in hand with the common goal of protecting public health.
Consumption of a Beverage Containing Aspartame and Acesulfame K for Two Weeks Does Not Adversely Influence Glucose Metabolism in Adult Males and Females: A Randomized Crossover Study
Authors: Kim Yoona , Keogh Jennifer B. , Clifton Peter M.
Published: December 2020

There is an association between the consumption of artificial sweeteners and Type 2 diabetes in cohort studies, but intervention studies do not show a clear elevation of blood glucose after the use of artificial sweeteners. The objective of this study was to examine whether two commonly used artificial sweeteners had an adverse effect on glucose control in normal-weight subjects, and in overweight and obese subjects when consumed for 2 weeks. In the study, 39 healthy subjects (body-mass index, kg/m2) (18–45) without Type 2 diabetes with an age of 18–75 years were randomly assigned to 0.6 L/day of an artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) or 0.6 L/day of mineral water for 2 weeks each in a crossover study. There was a 4 week washout period with no drinks consumed. Glucose levels were read by a continuous glucose monitor (CGM) during each 2 week period. A 75 g oral glucose-tolerance test (OGTT) was performed at the beginning and end of each intervention period. Blood samples were collected at baseline, and 1 and 2 h for glucose and insulin. A 2 week intake of artificially sweetened beverage (ASB) did not alter concentrations of fasting glucose and fasting insulin, the area under the curve (AUC) for OGTT glucose and insulin, the incremental area under the curve (iAUC) for OGTT glucose and insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and the Matsuda index compared with the baseline and with the changes after a 2 week intake of mineral water. Continuous 2 week glucose concentrations were not significantly different after a 2 week intake of ASB compared with a 2 week intake of mineral water. This study found no harmful effect of the artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) on glucose control when consumed for 2 weeks by people without Type 2 diabetes.
Older People’s Use and Nonuse of the Internet in Sweden
Authors: Anderberg Peter , Skär Lisa , Abrahamsson Linda , Berglund Johan Sanmartin
Published: December 2020

The use of the internet has considerably increased over recent years, and the importance of internet use has also grown as services have gone online. Sweden is largely an information society like other countries with high reported use amongst European countries. In line with digitalization development, society is also changing, and many activities and services today take place on the internet. This development could potentially lead to those older persons who do not use the internet or do not follow the development of services on the internet finding it difficult to take part in information and activities that no longer occur in the physical world. This has led to a digital divide between groups, where the older generations (60+), in particular, have been affected. In a large study of Sweden’s adult population in 2019, 95 percent of the overall population was said to be internet users, and the corresponding number for users over 66 years of age was 84%. This study shows that the numbers reported about older peoples’ internet use, most likely, are vastly overestimated and that real use is significantly lower, especially among the oldest age groups. We report that 62.4% of the study subjects are internet users and that this number most likely also is an overestimation. When looking at nonresponders to the questionnaire, we find that they display characteristics generally attributed to non-use, such as lower education, lower household economy, and lower cognitive functioning.
Cyberincivility Experience of Korean Clinical Nurses in the Workplace: A Qualitative Content Analysis
Authors: Kim Sang Suk , Song Ho Jeong , Lee Jung Jae
Published: December 2020

Although clinical nurses use online platforms to acquire health-related information and communicate with other healthcare providers, there are increasing reports on their incivility exposure in cyberspace. However, an in-depth understanding of their cyberincivility experience is lacking. This study aimed to identify Korean clinical nurses’ perception and experience of cyberincivility. A qualitative study was conducted. Twenty clinical nurses from seven private and public hospitals in the Seoul metropolitan area were recruited using purposive sampling. Individual semi-structured interviews were conducted with the nurses from June to September 2019. Conventional content analysis was applied for the interview data analysis. Clinical nurses perceived cyberincivility as disrespectful and condemning behavior as users hide under the shield of anonymity to persecute others without fear of retribution. Four themes regarding participants’ cyberincivility experience emerged: unprofessional behavior, hierarchical communication, lack of respect and morality, and forming an inefficient work environment. The results of this study provide an understanding regarding clinical nurses’ experience of cyberincivility that goes beyond that of previous studies, which mainly focused on students. These results could increase awareness of cyberincivility among clinical nurses, and provide key information for the design of cybercivility educational programs and guidelines to curb cyberincivility, nurture professional online communication, and consequently improve quality of care.
Dental Care Access and the Elderly: What Is the Role of Teledentistry? A Systematic Review
Authors: Aquilanti Luca , Santarelli Andrea , Mascitti Marco , Procaccini Maurizio , Rappelli Giorgio
Published: December 2020

A high level of unmet oral health needs is very common among elderly people. In a society that is getting older and that has been hit so hard by the coronavirus pandemic, the development of new strategies aimed at enhancing general and oral health status should be crucial in order to promote healthy aging. The aim of this systematic review is to assess the feasibility of Teledentistry in communities or in a domiciliary setting where elderly people live. A structured and systematic research was performed on the major electronic databases for studies published in English until 30 June 2020: the PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL databases. A total of 13 articles were identified through database searching using combinations of keywords. Out of 13 papers, eight abstracts were reviewed to assess if they were coherent with the aim of the study, and full texts were retrieved. After abstract reviews, seven articles were selected for closer inspection. Of these, six were assessed for eligibility. Four papers were aimed at assessing patients and health practitioners experiences about Teledentistry, three studies reported a cost analysis and cost description of Teledentistry in residential aged care facilities, and two studies investigated the feasibility and accuracy of Teledentistry for diagnosis dental pathology. The implementation of Teledentistry in residential aged care facilities and in home-assistance programs could be a viable tool for the management of oral care in people who cannot access dental care.
“Who Cares?”: The Acceptance of Decentralized Wastewater Systems in Regions without Water Problems
Authors: Gómez-Román Cristina , Lima Luisa , Vila-Tojo Sergio , Correa-Chica Andrea , Lema Juan , Sabucedo José-Manuel
Published: December 2020

There is a growing interest in decentralized wastewater treatment systems, especially in regions with water scarcity problems or water management issues. This study aims to determine whether the perceived advantages and disadvantages (leading to acceptance) of decentralized wastewater plants in such regions are the same in regions where the population is not aware of these water issues. Firstly, this study systematically reviews previous findings on public perceptions of the acceptance of decentralized wastewater treatment systems. Then, the study details the results of a focus group study to determine whether the elements identified in the literature are also relevant in a region where people are unaware of water problems. The results show that a lack of awareness of water issues seems to be a critical factor influencing acceptance. Reframing the usefulness of these systems by focusing on other aspects, such as environmental sustainability, is key.
Can Neurocognitive Function Predict Lower Extremity Injuries in Male Collegiate Athletes?
Authors: Ha Sunghe , Jeong Hee Seong , Park Sang-Kyoon , Lee Sae Yong
Published: December 2020

The purpose of this study is to demonstrate whether neurocognitive evaluation can confirm the association between neurocognitive level and postural control and to analyze the relationship between neurocognitive level and acute musculoskeletal injury in male non-net sports athletes. Seventy-seven male non-net sports athletes participated in this study. The Standardized Assessment of Concussion (SAC), Landing Error Scoring System (LESS), Balance Error Scoring System (BESS), and Star Excursion Balance Test (SEBT) were used for testing; we collected data related to injury history for six months after testing. Pearson’s correlation analysis, logistic regression, and the independent sample t-test were used for statistical analysis. The correlation between SAC and SEBT results was weak to moderate (p < 0.05). Eleven of the seventy-seven participants experienced acute lower limb injuries. SAC, LESS, BESS, and SEBT results have no effect on the occurrence of acute lower extremity injuries (p > 0.05) and were not statistically different between the injured and non-injured groups (p > 0.05). Therefore, using the SAC score alone to determine the risk factor of lower extremity injuries, except in the use of assessment after a concussion, should be cautioned against.
Diet Quality Compared to the Nutritional Knowledge of Polish, German, and Slovakian University Students—Preliminary Research
Authors: Suliga Edyta , Cieśla Elżbieta , Michel Sven , Kaducakova Helena , Martin Titus , Śliwiński Grzegorz , Braun Alexander , Izova Marcela , Lehotska Maria , Kozieł Dorota , Głuszek Stanisław
Published: December 2020

The eating habits of students differ significantly from those recommended by health practitioners. The aim of this study was to find differences related to diet quality and knowledge on nutrition among Polish, German, and Slovakian students as well as to examine which factors differentiate the diet quality of students from these three countries. The study was conducted on a group of 394 university students from Poland, Germany, and Slovakia. The assessment of diet quality and knowledge on food and nutrition was done with the use of the Dietary Habits and Nutrition Beliefs Questionnaire. The diet of German students was characterized by a significantly higher consumption of legume-based foods, vegetables, and fruit compared to Polish students and Slovakian participants (p < 0.001). The diet of the Poles was characterized by a high consumption of cured meat, smoked sausages, hot dogs, white bread and bakery products, butter, fried foods, and energy drinks. The most important factors significantly associated with diet quality involved the country, place of residence, Body Mass Index (BMI), physical activity, and time spent watching TV or using a computer. Polish students were characterized by the highest level of knowledge on food and nutrition (p < 0.001). However, it was not reflected in their diet. The authorities of universities should aim to provide students with access to canteens on campuses which would offer the possibility of consumption of both affordable and healthy meals.
Learning a Motor Skill from Video and Static Pictures in Physical Education Students—Effects on Technical Performances, Motivation and Cognitive Load
Authors: H’mida Cyrine , Degrenne Olivier , Souissi Nafaa , Rekik Ghazi , Trabelsi Khaled , Jarraya Mohamed , Bragazzi Nicola Luigi , Khacharem Aïmen
Published: December 2020

The purpose of the current study was to compare the effectiveness of a video and three different formats of static pictures (simultaneous-permanent pictures, sequential-transient pictures and sequential-permanent pictures) on the acquisition and retention of a complex judo skill in novice young adults. One hundred and thirty-three first-year students in the certificate in Physical Education (PE) were randomly assigned to either: a static-simultaneous-permanent pictures condition (n = 30), a static-sequential-transient pictures condition (n = 29), a static-sequential permanent pictures condition (n = 36) or a video condition (n = 38). They were instructed to observe and reproduce a complex judo technique (Ippon-Seoi-Nage) immediately after the learning phase (including a sequence of three trials—the acquisition phase) and after one week without observation (the retention phase). The results showed that the continuous video generated better learning performances than all static pictures formats. Moreover, it has been shown that sequential-permanent pictures presentation was more effective than static simultaneous-permanent pictures and sequential-transient pictures. In addition to the human movement effect, complementary explanations in terms of cognitive load theory, perceptual continuity, mental animation and intrinsic motivation are suggested. Implications of the results for the effective design of instructional materials within PE context are discussed.
Comparison of Oral Health Impact Profile (OHIP-14) Values in Cancer Survivor Patients Treated Orthodontically with Either Rapid or Standard Duration Protocols of Treatment—A Prospective Case–Control Study
Authors: Mitus-Kenig Maria , Derwich Marcin , Czochrowska Ewa , Pawlowska Elzbieta
Published: December 2020

Background: The aim of the study was to compare the oral-health-related quality of life (OHRQoL) between cancer survivors: with rapid orthodontic treatment (TX) (up to 12 months) and standard TX (orthodontic treatment time longer than 16 months). Methods: There were 76 cancer survivors (48 women and 28 men) allocated into groups with rapid (36 people) or standard (40 people) duration of TX. OHRQoL was assessed on the basis of Oral Health Impact Profile (OHIP-14) values, measured before TX, 2 weeks and 3 months after the onset of TX, and after the end of TX. A repeated ANOVA test was used to check the statistical significance between the scores. Results: There were no significant differences regarding the OHIP-14 values between the examined groups at all stages of the examination. Both groups presented significant (p < 0.001) improvement of the values of OHRQoL at the end of TX comparing to the values achieved before the onset of TX. Conclusions: Duration of orthodontic treatment by itself had no impact on oral-health-related quality of life.
Responsible Gambling Telephone Intervention to High-Risk Gamblers by a State-Owned Gambling Operator in Sweden: Study Protocol for a Study on Effectiveness, User Satisfaction, and Acceptability
Authors: Håkansson Anders , Franklin Katja , Dahlström Maria , Lyckberg Axel
Published: December 2020

Gambling disorder is associated with severe financial, social, and psychological consequences, but treatment-seeking rates have been described to be low. Apart from formal treatment, motivational interventions in nontreatment-seeking high-risk gamblers have been shown to be promising. However, little is known about the effectiveness and acceptability of such motivational interventions carried out by a gambling operator as part of the company’s responsible gambling policies. Early experiences of such interventions are limited by the risk that gambling in individuals reached with the intervention may continue with a different gambling operator. The present study aims to evaluate effectiveness and user acceptability of a responsible gambling intervention continuously carried out by the Swedish state-owned gambling operator Svenska Spel Sport & Casino. This intervention for high-risk gamblers, identified either through substantial monetary losses or through a voluntary self-test by the gambler, includes a motivational telephone intervention aiming to encourage the gambler to set deposit limits, practice self-exclusion, or seek help. This protocol paper describes the two-tailed evaluation of this intervention: (1) A retrospective, register-based study of the effectiveness of the motivational intervention on gambling expenditures, deposit limits, and self-exclusions in comparison to control individuals not reached by the intervention, including all clients reached or attempted to be reached during September 2019–April 2020 (total n = 3626), as well as a one-to-one matched comparison of clients reached (n = 1404) and not reached; and (2) a prospective web survey study in individuals reached by the same ongoing telephone intervention practice from November 2020 (target n = 200), measuring clients’ attitudes to the intervention, perceived effects of the intervention on gambling, and their self-reported gambling on all operators after the intervention.
The Bittersweet Effects of COVID-19 on Mental Health: Results of an Online Survey among a Sample of the Dutch Population Five Weeks after Relaxation of Lockdown Restrictions
Authors: Gijzen Mandy , Shields-Zeeman Laura , Kleinjan Marloes , Kroon Hans , van der Roest Henriëtte , Bolier Linda , Smit Filip , de Beurs Derek
Published: December 2020

Previous research shows that crises can have both negative and positive mental health effects on the population. The current study explored these effects in the context of the COVID-19 pandemic after relaxation of governmental measures. An online survey was administered among a representative sample of the Dutch population (n = 1519) in June 2020, ten weeks after the peak of COVID-19 had passed, and five weeks after restrictions were relaxed. Participants were asked about mental health, adverse events during COVID-19, and about any positive effects of the pandemic. Most participants (80%, n = 1207) reported no change in mental health since the COVID-19 pandemic. This was also the case among respondents who had experienced an adverse event. Protective factors of mental health were being male and high levels of positive mental well-being. Risk factors were emotional loneliness and the experience of adverse life events. Social loneliness was positively associated with stable mental health, stressing the importance of meaningful relationships. Note that 58% of participants reported positive effects of the pandemic, the most common of which were rest, working from home, and feeling more socially connected. In summary, 10 weeks after the start of the crisis, and 5 weeks after relaxation of the restrictions, most people remained stable during the crisis, and were even able to report positive effects.
Comparison of Bisulfite Pyrosequencing and Methylation-Specific qPCR for Methylation Assessment
Authors: De Chiara Loretta , Leiro-Fernandez Virginia , Rodríguez-Girondo Mar , Valverde Diana , Botana-Rial María Isabel , Fernández-Villar Alberto
Published: December 2020

Different methodological approaches are available to assess DNA methylation biomarkers. In this study, we evaluated two sodium bisulfite conversion-dependent methods, namely pyrosequencing and methylation-specific qPCR (MS-qPCR), with the aim of measuring the closeness of agreement of methylation values between these two methods and its effect when setting a cut-off. Methylation of tumor suppressor gene p16/INK4A was evaluated in 80 lung cancer patients from which cytological lymph node samples were obtained. Cluster analyses were used to establish methylated and unmethylated groups for each method. Agreement and concordance between pyrosequencing and MS-qPCR was evaluated with Pearson’s correlation, Bland–Altman, Cohen’s kappa index and ROC curve analyses. Based on these analyses, cut-offs were derived for MS-qPCR. An acceptable correlation (Pearson’s R2 = 0.738) was found between pyrosequencing (PYRmean) and MS-qPCR (NMP; normalized methylation percentage), providing similar clinical results when categorizing data as binary using cluster analysis. Compared to pyrosequencing, MS-qPCR tended to underestimate methylation for values between 0 and 15%, while for methylation >30% overestimation was observed. The estimated cut-off for MS-qPCR data based on cluster analysis, kappa-index agreement and ROC curve analysis were much lower than that derived from pyrosequencing. In conclusion, our results indicate that independently of the approach used for estimating the cut-off, the methylation percentage obtained through MS-qPCR is lower than that calculated for pyrosequencing. These differences in data and therefore in the cut-off should be examined when using methylation biomarkers in the clinical practice.
Fatty-Acid-Binding Protein 4 as a Novel Contributor to Mononuclear Cell Activation and Endothelial Cell Dysfunction in Atherosclerosis
Authors: Wu Yen-Wen , Chang Ting-Ting , Chang Chia-Chi , Chen Jaw-Wen
Published: December 2020

Background—Elevated circulating fatty-acid-binding protein 4 (FABP4) levels may be linked with cardiovascular events. This study aimed to investigate the mechanistic role of FABP4 in atherosclerosis. Methods—We recruited 22 patients with angiographically proven coronary artery disease (CAD) and 40 control subjects. Mononuclear cells (MNCs) and human coronary endothelial cells (HCAECs) were used for in vitro study. Results—Patients with CAD were predominantly male with an enhanced prevalence of hypertension, diabetes, and smoking history. FABP4 concentrations were up-regulated in culture supernatants of MNCs from CAD patients, which were positively correlated with the patients’ age, waist–hip ratio, body mass index, serum creatinine, type 2 diabetes, and the presence of hypertension. The adhesiveness of HCAECs to monocytic cells can be activated by FABP4, which was reversed by an FABP4 antibody. FABP4 blockade attenuated the oxidized low-density lipoprotein (oxLDL)-induced expression of ICAM-1, VCAM-1, and P-selectin. FABP4 impaired the tube formation and migration via the ERK/JNK/STAT-1 signaling pathway. FABP4 suppressed phosphorylation of eNOS and expression of SDF-1 protein, both of which can be reversed by treatment with VEGF. Blockade of FABP4 also improved the oxLDL-impaired cell function. Conclusion—We discovered a novel pathogenic role of FABP4 in MNC activation and endothelial dysfunction in atherosclerosis. FABP4 may be a therapeutic target for modulating atherosclerosis.
Endoglin: An ‘Accessory’ Receptor Regulating Blood Cell Development and Inflammation
Authors: Meurer Steffen K. , Weiskirchen Ralf
Published: December 2020

Transforming growth factor-β1 (TGF-β1) is a pleiotropic factor sensed by most cells. It regulates a broad spectrum of cellular responses including hematopoiesis. In order to process TGF-β1-responses in time and space in an appropriate manner, there is a tight regulation of its signaling at diverse steps. The downstream signaling is mediated by type I and type II receptors and modulated by the ‘accessory’ receptor Endoglin also termed cluster of differentiation 105 (CD105). Endoglin was initially identified on pre-B leukemia cells but has received most attention due to its high expression on activated endothelial cells. In turn, Endoglin has been figured out as the causative factor for diseases associated with vascular dysfunction like hereditary hemorrhagic telangiectasia-1 (HHT-1), pre-eclampsia, and intrauterine growth restriction (IUPR). Because HHT patients often show signs of inflammation at vascular lesions, and loss of Endoglin in the myeloid lineage leads to spontaneous inflammation, it is speculated that Endoglin impacts inflammatory processes. In line, Endoglin is expressed on progenitor/precursor cells during hematopoiesis as well as on mature, differentiated cells of the innate and adaptive immune system. However, so far only pro-monocytes and macrophages have been in the focus of research, although Endoglin has been identified in many other immune system cell subsets. These findings imply a functional role of Endoglin in the maturation and function of immune cells. Aside the functional relevance of Endoglin in endothelial cells, CD105 is differentially expressed during hematopoiesis, arguing for a role of this receptor in the development of individual cell lineages. In addition, Endoglin expression is present on mature immune cells of the innate (i.e., macrophages and mast cells) and the adaptive (i.e., T-cells) immune system, further suggesting Endoglin as a factor that shapes immune responses. In this review, we summarize current knowledge on Endoglin expression and function in hematopoietic precursors and mature hematopoietic cells of different lineages.
Role of Nucleotide Excision Repair in Cisplatin Resistance
Authors: Duan Mingrui , Ulibarri Jenna , Liu Ke Jian , Mao Peng
Published: December 2020

Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed.
The STING-IFN-β-Dependent Axis Is Markedly Low in Patients with Relapsing-Remitting Multiple Sclerosis
Authors: Masanneck Lars , Eichler Susann , Vogelsang Anna , Korsen Melanie , Wiendl Heinz , Budde Thomas , Meuth Sven G.
Published: December 2020

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.
Gas Chromatography–Mass Spectrometry Based Approach for the Determination of Methionine-Related Sulfur-Containing Compounds in Human Saliva
Authors: Piechocka Justyna , Wieczorek Monika , Głowacki Rafał
Published: December 2020

Gas chromatography–mass spectrometry technique (GC-MS) is mainly recognized as a tool of first choice when volatile compounds are determined. Here, we provide the credible evidence that its application in analysis can be extended to non-volatile sulfur-containing compounds, to which methionine (Met), homocysteine (Hcy), homocysteine thiolactone (HTL), and cysteine (Cys) belong. To prove this point, the first method, based on GC-MS, for the identification and quantification of Met-related compounds in human saliva, has been elaborated. The assay involves simultaneous disulfides reduction with tris(2-carboxyethyl)phosphine (TCEP) and acetonitrile (MeCN) deproteinization, followed by preconcentration by drying under vacuum and treatment of the residue with a derivatizing mixture containing anhydrous pyridine, N-trimethylsilyl-N-methyl trifluoroacetamide (MSTFA), and trimethylchlorosilane (TMCS). The validity of the method was demonstrated based upon US FDA recommendations. The assay linearity was observed over the range of 0.5–20 µmol L−1 for Met, Hcy, Cys, and 1–20 µmol L−1 for HTL in saliva. The limit of quantification (LOQ) equals 0.1 µmol L−1 for Met, Hcy, Cys, while its value for HTL was 0.05 µmol L−1. The method was successfully applied to saliva samples donated by apparently healthy volunteers (n = 10).
Compact Bidirectional Promoters for Dual-Gene Expression in a Sleeping Beauty Transposon
Authors: He Kevin , Rad S. M. Ali Hosseini , Poudel Aarati , McLellan Alexander Donald
Published: December 2020

Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoter systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact, bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron/exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptor (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual-CAR cassettes, is limited.
New Eugenol Derivatives with Enhanced Insecticidal Activity
Authors: Fernandes Maria José G. , Pereira Renato B. , Pereira David M. , Fortes A. Gil , Castanheira Elisabete M. S. , Gonçalves M. Sameiro T.
Published: December 2020

Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.
Essential Oils Biofilm Modulation Activity, Chemical and Machine Learning Analysis—Application on Staphylococcus aureus Isolates from Cystic Fibrosis Patients
Authors: Papa Rosanna , Garzoli Stefania , Vrenna Gianluca , Sabatino Manuela , Sapienza Filippo , Relucenti Michela , Donfrancesco Orlando , Fiscarelli Ersilia , Artini Marco , Selan Laura , Ragno Rino
Published: December 2020

Bacterial biofilm plays a pivotal role in chronic Staphylococcus aureus (S. aureus) infection and its inhibition may represent an important strategy to develop novel therapeutic agents. The scientific community is continuously searching for natural and “green alternatives” to chemotherapeutic drugs, including essential oils (EOs), assuming the latter not able to select resistant strains, likely due to their multicomponent nature and, hence, multitarget action. Here it is reported the biofilm production modulation exerted by 61 EOs, also investigated for their antibacterial activity on S. aureus strains, including reference and cystic fibrosis patients’ isolated strains. The EOs biofilm modulation was assessed by Christensen method on five S. aureus strains. Chemical composition, investigated by GC/MS analysis, of the tested EOs allowed a correlation between biofilm modulation potency and putative active components by means of machine learning algorithms application. Some EOs inhibited biofilm growth at 1.00% concentration, although lower concentrations revealed different biological profile. Experimental data led to select antibiofilm EOs based on their ability to inhibit S. aureus biofilm growth, which were characterized for their ability to alter the biofilm organization by means of SEM studies.
Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo
Authors: Chang Sukkum Ngullie , Dey Debasish Kumar , Oh Seong Taek , Kong Won Ho , Cho Kiu Hyung , Al-Olayan Ebtesam M. , Hwang Buyng Su , Kang Sun Chul , Park Jae Gyu
Published: December 2020

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 μg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.
The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress, and Inflammation in Protective and Adaptive Responses
Authors: Rochette Luc , Mazini Loubna , Malka Gabriel , Zeller Marianne , Cottin Yves , Vergely Catherine
Published: December 2020

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.
AGE-RAGE Axis Stimulates Oxidized LDL Uptake into Macrophages through Cyclin-Dependent Kinase 5-CD36 Pathway via Oxidative Stress Generation
Authors: Yashima Hironori , Terasaki Michishige , Sotokawauchi Ami , Matsui Takanori , Mori Yusaku , Saito Tomomi , Osaka Naoya , Kushima Hideki , Hiromura Munenori , Ohara Makoto , Fukui Tomoyasu , Yamagishi Sho-ichi
Published: December 2020

Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, the underlying molecular mechanism remains unclear. Since cyclin-dependent kinase 5 (Cdk5) is reported to modulate inflammatory responses in macrophages, we investigated whether Cdk5 could be involved in AGE-induced CD36 gene expression and foam cell formation of macrophages. AGEs significantly increased Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and Cdk5 and CD36 gene expression in U937 human macrophages, all of which were inhibited by DNA aptamer raised against RAGE (RAGE-aptamer). Cdk5 and CD36 gene expression levels were correlated with each other. An antioxidant, N-acetyl-l-cysteine, mimicked the effects of RAGE-aptamer on AGE-exposed U937 cells. A selective inhibitor of Cdk5, (R)-DRF053, attenuated the AGE-induced Dil-ox-LDL uptake and CD36 gene expression, whereas anti-CD36 antibody inhibited the Dil-ox-LDL uptake but not Cdk5 gene expression. The present study suggests that AGEs may stimulate ox-LDL uptake into macrophages through the Cdk5–CD36 pathway via RAGE-mediated oxidative stress.
Enhancement in Phospholipase D Activity as a New Proposed Molecular Mechanism of Haloperidol-Induced Neurotoxicity
Authors: Krzystanek Marek , Krzystanek Ewa , Skałacka Katarzyna , Pałasz Artur
Published: December 2020

Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were sacrificed for a time equal to the half-life of the antipsychotic drug in the brain, then the membranes in which PLD activity was determined were isolated from the tissue. The results indicate that only haloperidol in a higher dose increases the activity of phospholipase D. Such a mechanism of action of haloperidol has not been described previously. Induction of PLD activity by haloperidol may be related to its mechanism of cytotoxicity. The finding could justify the use of PLD inhibitors as protective drugs against the cytotoxicity of first-generation antipsychotic drugs like haloperidol.