bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Quantitative Assessment of Ochratoxin A, Patulin, 5-Hydroxymethylfurfural, and Bisphenol A in Fruit Drinks Using HPLC with Diode Array-Fluorimetric Detection
Authors: Hassan Norfarizah Hanim , Othman Haneen Ibrahim Ahmad Al , Abdul Malek Nur Rabiatutadawiah , Zulkurnain Musfirah , Saad Bahruddin , Wong Yong Foo
Published: November 2020

The analysis of regulated contaminants in fruit drinks often requires suitable validated and rapid analytical methods for cost-effective food control, and is of considerable interest among the fruit beverage industry. This study demonstrated a rapid and sensitive high-performance liquid chromatography approach for the simultaneous determination of ochratoxin A (OTA), patulin (PAT), 5-hydroxymethylfurfural (HMF), and bisphenol A (BPA) in various fruit drinks. The separations were achieved using a C18 core-shell column with both photo-diode array and fluorimetric detections connected in series. A gradient system consisting of methanol and 0.1% formic acid at a flow rate of 1.2 mL min−1, thermostated at 35 °C, provided fast elution with run time <9 min. Sample pretreatment was optimised to enable extraction of all analytes from fruit drink matrices. The optimised method was validated. Correlation coefficients of R > 0.99 were achieved with detection limits of 0.5 ng mL−1 (OTA), 1.1 ng mL−1 (PAT), 7.9 ng mL−1 (HMF), and 1.0 ng mL−1 (BPA). Recoveries ranged from 82% to 99%. Good relative standard deviations for intraday retention times (≤3.54%) and peak area (≤3.5%) were achieved. The developed multi-contaminants analysis method was successfully applied to determine OTA, PAT, HMF, and BPA in various fruit drinks.
Antifungal Activity of Aromatic Plants of the Lamiaceae Family in Bread
Authors: Skendi Adriana , Katsantonis Dimitrios Ν. , Chatzopoulou Paschalina , Irakli Maria , Papageorgiou Maria
Published: November 2020

The antifungal effect of aromatic plants (oregano, thyme, and Satureja) in dry form and as essential oils was evaluated in vitro (in potato dextrose agar (PDA)) and in bread against two phytopathogenic fungi found in food (Aspergillusniger and Penicillium). Gas and liquid chromatography were used to analyze essential oils attained by hydrodistillation of the aerial parts of the aromatic plants and of the dried plant aqueous solutions that were autoclaved for 20 min at 121 °C before analysis. Carvacrol, α-pinene, p-cymene, and γ-terpinene were the main components of the essential oils, whereas carvacrol, rosmarinic and caffeic acids were the main components of the water extracts. In vitro antifungal test results showed that the addition of plants in dry form had great antifungal potential against both fungal strains studied. Penicillium was more sensitive to the presence of aromatic plants than Aspergillus. Among the three plant species tested, thyme was the most potent antifungal against both fungi. For the bread product, all three aromatic plants studied showed inhibitory effects against both fungi. Results presented here suggest that oregano, thyme and Satureja incorporated in a bread recipe possess antimicrobial properties and are a potential source of antimicrobial ingredients for the food industry.
Associations between Pet Ownership and Frailty: A Systematic Review
Authors: Kojima Gotaro , Aoyama Reijiro , Taniguchi Yu
Published: November 2020

Frailty is defined as a state of increased vulnerability due to age-related decline in reserve and function across multiple physiological systems. Increasing physical activity level is considered to be a measure to counteract frailty. Some studies have indicated that pet owners are more engaged in physical activity than non-owners. We conducted a systematic review regarding associations between pet ownerships and frailty among community-dwelling older adults and critically assessed the findings. PubMed was searched in April 2020 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for cross-sectional or prospective studies examining associations between pet ownership and frailty in community-dwelling older adults with a mean age of 60 or above. A supplementary search was done using Google Scholar. Identified articles were reviewed by two investigators independently and assessed for methodological quality. The search identified 48 studies, among which three studies (two cross-sectional and one prospective) were included in this review. These studies suggested that pet ownership may be associated with a lower risk of frailty. This systematic review found only a limited amount of relevant research. More research is needed to establish the link between pet ownership and frailty as well as healthy aging and well-being.
Regional Variability in the Access to Cardiac Rehabilitation in Poland
Authors: Jankowiak Maciej , Rój Justyna
Published: November 2020

Equitable access to cardiological rehabilitation services is one of the important elements in the effectiveness of the treatment of cardiovascular diseases as cardiological rehabilitation is an important part of circulatory system disease prevention and treatment. However, in many countries among others, Poland suffers from the underutilization of cardiac rehabilitation services. Cardiovascular diseases are the worldwide number one cause of mortality, morbidity, and disability and are responsible for the substantial increase in health care costs. Thus, the aim of the research was the analysis of geographical accessibility to cardiac rehabilitation services in Poland. Perkal’s method was employed in this research. The conducted research allowed to recognize the regional variation, but also made it possible to classify Polish voivodeships in terms of the level of availability achieved. This enables the identification of voivodeships that provide a good, or even very good, access to cardiology rehabilitation services and those characterized by low, or very low access. It was found that there was a slight regional variability in the access to cardiological rehabilitation services. However, the sufficient development of a rehabilitation infrastructure has been also recognized.
The Meaning of Work and Self-Management Experiences among Elderly Workers with Multiple Chronic Diseases: A Qualitative Study
Authors: Kim Juah , Ha Jiyeon
Published: November 2020

With population aging, increasingly many elderly individuals are expected to participate in economic activities. Elderly workers have a higher prevalence of multiple chronic diseases, making it necessary to examine elderly workers’ experiences of health-related self-management in work environments. This qualitative study investigated the meaning of work and health-related self-management experiences among elderly workers with multiple chronic diseases. The study participants were elderly workers residing in South Korea (65 years old or older) with at least two chronic diseases. Twelve participated in individual interviews, which were audio-recorded and transcribed. Qualitative content analysis was conducted with the transcribed data. Six themes, 21 sub-themes, and 40 codes were derived. The themes were “benefit of work on health and life”, “adaptation to a new work environment”, “endurance”, “continuous efforts to maintain health”, “difficulties in self-management”, and “requirements for health promotion”. The participants experienced difficulties in health-related self-management due to time constraints, poor work environment, and financial burdens. However, participants expressed their desire to invest effort into managing their physical and psychological health and to work as long as possible. Programs that consider the aging and health-related characteristics of elderly workers and their work environments should be developed and implemented.
Adolescent Participation in Research, Policies and Guidelines for Chronic Disease Prevention: A Scoping Review Protocol
Authors: Mandoh Mariam , Mihrshahi Seema , Cheng Hoi Lun , Redfern Julie , Partridge Stephanie R.
Published: November 2020

Adolescents (10–24 years old) account for 23% of the global population. Physical inactivity, suboptimal dietary intake, overweight, and obesity during adolescence are risk factors associated with chronic disease development into adulthood. Research, policies, and guidelines that seek to prevent chronic disease risk factor development rarely engage adolescents in planning and decision-making processes. The aims of this review are to investigate (i) how adolescents currently participate in research, policy, and guidelines for reduction of chronic disease risk factors, and (ii) provide recommendations to optimize adolescent participation in future research, policy, and guideline decision making for chronic disease prevention. A systematic scoping review of the health peer-review research, policy, and guidelines, using Arksey and O’Malley’s six-stage framework, will be conducted. Participatory outcomes will be assessed based on the Lansdown-UNICEF conceptual framework for measuring adolescent participation. Classified as consultative, collaborative, or adolescent-led according to the degree of influence and power adolescents possess in the decision- making processes. Consultation with adolescents via digital surveys and focus groups will provide further information, perspective, and insight. Qualitative data will be analyzed by descriptive numerical summary and qualitative content analytical techniques. The title of this protocol is registered with Joanna Briggs Institute and Open Science Framework, doi:10.17605/OSF.IO/E3S64.
Clinical Use of Acid Suppressants and Risk of Dementia in the Elderly: A Pharmaco-Epidemiological Cohort Study
Authors: Chen Liang-Yu , Lin Huey-Juan , Wu Wen-Tung , Chen Yong-Chen , Chen Cheng-Li , Kao Jing , You San-Lin , Chou Yu-Ching , Sun Chien-An
Published: November 2020

Background: Results of studies regarding the potential link between acid suppressant use and dementia risk are inconsistent. This study aimed to evaluate the association of cumulative exposure to histamine 2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) with dementia risk in an Asian older cohort aged ≥65 years. Methods: Patients initiating H2RA (the H2RA user cohort, n = 21,449) or PPI (the PPI user cohort, n = 6584) and those without prescription for H2RA (the H2RA non-user cohort, n = 21,449) or PPI (the PPI non-user cohort, n = 6584) between 1 January 2000 and 31 December 2005 without a prior history of dementia were identified from Taiwan’s National Health Insurance Research Database (NHIRD). The outcome of interest was all-cause dementia. Patients’ exposure to H2RAs or PPIs was followed-up from dates of initial prescription to the earliest outcome of incident dementia, death, or the end of 2013. Potential associations between acid suppressant use and dementia risk were analyzed using time-dependent Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After mutual adjustment for H2RA and PPI use and other potential confounders, patients with H2RA use had significantly higher risk of developing dementia as compared to those not treated with H2RAs (adjusted HR, 1.84; 95% CI, 1.49–2.20). Likewise, PPI users had significantly elevated risk of dementia compared to PPI non-users (adjusted HR, 1.42; 95% CI, 1.07–1.84). Conclusions: Our results indicate that exposures to H2RAs and PPIs are associated with increased dementia risk.
The Health Consequences of Neocolonialism for Latin American Immigrant Women Working as Caregivers in Spain: A Multisite Qualitative Analysis
Authors: Briones-Vozmediano Erica , Rivas-Quarneti Natalia , Gea-Sánchez Montserrat , Bover-Bover Andreu , Carbonero Maria Antonia , Gastaldo Denise
Published: November 2020

In Spain, most jobs available for Latin American immigrant women are in intimate labour (caregiving and domestic work). This work is usually performed under informal employment conditions. The objective of this study was to explain how the colonial logic mediates the experiences of Latin American women working in intimate labour in Spain, and the effects of such occupation on their health and wellbeing, using a decolonial theoretical framework. A multi-site secondary data analysis of qualitative data from four previous studies was performed utilizing 101 interviews with Latin American immigrant women working as caregivers in Spain. Three interwoven categories show how the dominant colonial logic in Spain creates low social status and precarious jobs, and naturalizes intimate labour as their métier while producing detrimental physical and psychosocial health consequences for these immigrant caregivers. The caregivers displayed several strategies to resist and navigate intimate labour and manage its negative impact on health. Respect and integration into the family for whom they work had a buffering effect, mediating the effects of working conditions on health and wellbeing. Based on our analysis, we suggest that employment, social, and health protection laws and strategies are needed to promote a positive working environment, and to reduce the impact of caregiving work for Latin American caregivers.
Synergistic Effects and Sex Differences in Anthropometric Measures of Obesity and Elevated High-Sensitivity C-Reactive Protein Levels
Authors: Nari Fatima , Jang Bich Na , Kim Gyu Ri , Park Eun-Cheol , Jang Sung-In
Published: November 2020

Background: It remains unclear which anthropometric measure best predicts elevated high-sensitivity C-reactive protein (hs-CRP) levels. This study investigated the association and synergistic interaction of two obesity indices with elevated hs-CRP levels in a national sample of Korean adults, stratified by sex. Methods: The present cross-sectional study used data from the 2015–2018 Korea National Health and Nutrition Examination Survey of 18,610 subjects aged ≥20 years after excluding those with missing variables. Multiple logistic regression analyses and chi-squared tests were performed to investigate the association between body mass index (BMI) and waist circumference (WC) with elevated hs-CRP levels. Interaction analysis was used to examine the synergistic effect between BMI and WC on the risk of having elevated hs-CRP levels. Results: Elevated hs-CRP levels exceeding 3 mg/L were present in 9.3% and 7.5% of men and women, respectively. The relationship between each obesity index and elevated hs-CRP levels was significant in women (high WC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24–2.54), high BMI (OR = 2.08, 95% CI = 1.58–2.74)) but not in men (high WC (OR = 1.19, 95% CI = 0.86–1.64), high BMI (OR = 0.99, 95% CI = 0.77–1.29)). Furthermore, combined measures of the two obesity indices and interaction analysis results revealed a synergistic association in men (OR = 1.57, 95% CI = 1.33–1.85; relative excess risk due to interaction (RERI) = 0.39, 95% CI = −0.09–0.86), and women (OR = 3.70, 95% CI = 3.09–4.43; RERI = 0.85, 95% CI = −0.06–1.75). Conclusion: BMI and WC were significantly associated with a risk of elevated hs-CRP levels in women but not in men. Nevertheless, significant synergistic interactions were seen in combined measures of BMI and WC, regardless of sex. These findings emphasize the need to use both measures of adiposity concurrently in the assessment of obesity and when identifying cardiovascular risk.
Experiences of a Teacher in Relation to the Student’s Feelings of Learned Helplessness
Authors: González-Calvo Gustavo
Published: November 2020

This paper is based on the concern of a novice physical education teacher to reinforce the self-esteem and motor competence sensations of students during lessons. This concern arises from the experiences gained as a student. I draw on autobiographical narratives to delve into how these experiences led me to develop a feeling of learned incompetence, a sense of failure within the educational system and, consequently, an obvious difficulty to shape my personal and professional identity. However, it is these same experiences that condition professional development and teaching practice. Thus, I attempt to break from pedagogical models and to offer a dignified and democratic education to students. I attempt to engage the reader by communicating the subjectivity of different moments in a provocative, fragmented, physical, and emotional manner. Thus, I share the concerns, reflections, and manner of working, as a teacher, in the form of autobiographical reports and class journals. The intention is to understand how this manner of working responds to the feelings of incompetence learned by school children.
How to Find Vacant Green Space in the Process of Urban Park Planning: Case Study in Ningbo (China)
Authors: Ji Shunwei , Ma Renfeng , Ren Liyan , Wang Caijuan
Published: November 2020

Nature-based recreation in urban areas is essential for the well-being of citizens. Park green space (PGS) is a necessary urban infrastructure and a critical step of urban planning and policy-making. The existing research on PGS only focuses on service allocation problems existing in the current urban development, ignoring changes in residential communities accessibility. This research provides new ideas to evaluate PGS. Based on parks and residential communities’ data, we adopt an improved Gaussian-based two-step floating catchment area (2SFCA) method to evaluate PGS accessibility in Ningbo (China) and its matching with different levels of residential areas. We present a case study in Ningbo, and discuss its implications for PGS management. This study contains two elements: (a) Compare the current and initial PGS accessibility of each community to accurately identify the communities with PGS vacancies. (b) Analyze and discuss the association between community accessibility and residential house prices. Compare the PGS coverage ratios of communities at different levels to determine the equity of PGS planning in Ningbo. We found that the level of PGS allocation in the central area of Ningbo is high. Obviously, high-value clusters are formed in Sanjiangkou, Zhenhai New Town, Southern and Eastern Yinzhou. The accessibility level in the middle area of Yinzhou is low, and there are super high accessibility residential communities in the outer city area. There is an exact period of green space vacancy in the middle and the outer area. The residential areas with ultra-high accessibility did not configure PGS services at the beginning of their construction. There is no noticeable difference in PGS accessibility of residential communities of different levels at present, but 149 low- and middle-income residential communities lack green space service when the construction was completed. High-end residential communities have priority on enjoying park green space services. Our study suggests that PGS accessibility should be studied temporally and spatially for each residential community. The Ningbo government should strengthen the balanced construction of green space in parks and guarantee green space services for low-end residential communities to improve green space equity.
The Determinants for Food Safety Push Notifications on Continuance Intention in an E-Appointment System for Public Health Medical Services: The Perspectives of UTAUT and Information System Quality
Authors: Lee Yu-Ping , Tsai Hsin-Yeh , Ruangkanjanases Athapol
Published: November 2020

Compared to other appointment methods in public hospitals, registering through the Internet or utilizing e-appointments, or registering online as an outpatient, can provide more information to the user. This research investigated the integration of unified theory of the acceptance and use of technology and information system quality in determining factors that influence the adoption of e-appointments by patients, based on the requirements of food safety consultation in Taiwan. Empirical data from 369 valid samples were assessed using Partial Least Squares (PLS). The key findings of this study indicated that patients’ acceptance of e-appointments was influenced by users’ perceptions (i.e., performance expectancy and facilitating conditions), along with information quality and service quality. The practical and academic implications are provided for future practitioners and scholars, and to enhance patients’ usage of e-appointments in their healthcare activities.
Mental Illness and Youth-Onset Homelessness: A Retrospective Study among Adults Experiencing Homelessness
Authors: Iwundu Chisom N. , Chen Tzu-An , Edereka-Great Kirsteen , Businelle Michael S. , Kendzor Darla E. , Reitzel Lorraine R.
Published: November 2020

Financial challenges, social and material instability, familial problems, living conditions, structural issues, and mental health problems have been shown to contribute to youth homelessness. Based on the paucity of literature on mental illness as a reason for youth homelessness, the current study retrospectively evaluated the association between the timing of homelessness onset (youth versus adult) and mental illness as a reason for homelessness among homeless adults living in homeless shelters and/or receiving services from homeless-serving agencies. Homeless participants (N = 919; 67.3% men) were recruited within two independent studies from Dallas and Oklahoma. Covariate-adjusted logistic regressions were used to measure associations between homelessness onset and mental illness as a reason for current homelessness, history of specific mental illnesses, the historical presence of severe mental illness, and severe mental illness comorbidity. Overall, 29.5% of the sample reported youth-onset homelessness and 24.4% reported mental illness as the reason for current homelessness. Results indicated that mental illness as a reason for current homelessness (AOR = 1.62, 95% CI = 1.12–2.34), history of specific mental illnesses (Bipolar disorder–AOR = 1.75, 95% CI = 1.24–2.45, and Schizophrenia/schizoaffective disorder–AOR = 1.83, 95% CI = 1.22–2.74), history of severe mental illness (AOR = 1.48, 95% CI = 1.04–2.10), and severe mental illness comorbidities (AOR = 1.30, 95% CI: 1.11–1.52) were each associated with increased odds of youth-onset homelessness. A better understanding of these relationships could inform needs for early interventions and/or better prepare agencies that serve at-risk youth to address precursors to youth homelessness.
Spatio-Temporal Distribution of Aedes Albopictus and Culex Pipiens along an Urban-Natural Gradient in the Ventotene Island, Italy
Authors: Manica Mattia , Riello Sara , Scagnolari Carolina , Caputo Beniamino
Published: November 2020

The distribution of mosquitos and their corresponding hosts is critical in public health to determine the risk of transmission for vector-borne diseases. In this pilot study conducted in the small Mediterranean island of Ventotene, a known stopover site for migratory birds, the spatio-temporal distribution of two major mosquito vectors is analyzed from the natural to urban environment. The results show that Aedes albopictus aggregates mostly near areas with a human presence and the urban landscape, while Culex pipiens is more spatio-temporally spread, as it can also be found in wilder and less anthropized areas where the availability of human hosts is limited. Culex pipiens is also active earlier in the year. From a microgeographical perspective, our results confirm the anthropophilic spatial distribution of Ae. Albopictus, while suggesting that the circulation of bird zoonosis, such as West Nile, could be favored by the Cx. pipiens distribution. The results highlight the different ecology of the vectors and the interplay with their hosts, even at a small scale. The current evidence may help in forecasting the risk of pathogen transmission and surveillance planning.
Analysis of Emergency Department Visits and Hospital Activity during Influenza Season, COVID-19 Epidemic, and Lockdown Periods in View of Managing a Future Disaster Risk: A Multicenter Observational Study
Authors: Casalino Enrique , Choquet Christophe , Bouzid Donia , Peyrony Olivier , Curac Sonja , Revue Eric , Fontaine Jean-Paul , Plaisance Patrick , Chauvin Anthony , Ghazali Daniel Aiham
Published: November 2020

ED-visits and through-ED admissions to medical/surgical wards (MSW) and intensive care unit (ICU) during influenza, COVID-19 and lockdown periods were evaluated in a four-hospital prospective observational study from November 2018 to March 2020. ED visit characteristics and main diagnostic categories were assessed. Analysis of 368,262 ED-visits highlighted a significantly increasing trend in ED-visits during influenza followed by a significantly decreasing trend after lockdown. For MSW-admissions, a pattern of growth during influenza was followed by a fall that began during COVID-19 pandemic and intensified during the lockdown. For ICU-admissions, a significant rise during the COVID-19 pandemic was followed by diminution during the lockdown period. During lockdown, significantly diminishing trends were shown for all diagnostic categories (between −40.8% and −73.6%), except influenza-like illness/COVID cases (+31.6%), Pulmonary embolism/deep vein thrombosis (+33.5%) and frequent users (+188.0%). The present study confirms an increase in demand during the influenza epidemic and during the initial phase of the COVID-19 epidemic, but a drop in activity during the lockdown, mainly related to non-COVID conditions. Syndromic surveillance of ILI cases in ED is a tool for monitoring influenza and COVID-19, and it can predict ED activity and the need for MSW and ICU beds.
Facilitating the Development of Deep Learning Models with Visual Analytics for Electronic Health Records
Authors: Hur Cinyoung , Wi JeongA , Kim YoungBin
Published: November 2020

Electronic health record (EHR) data are widely used to perform early diagnoses and create treatment plans, which are key areas of research. We aimed to increase the efficiency of iteratively applying data-intensive technology and verifying the results for complex and big EHR data. We used a system entailing sequence mining, interpretable deep learning models, and visualization on data extracted from the MIMIC-IIIdatabase for a group of patients diagnosed with heart disease. The results of sequence mining corresponded to specific pathways of interest to medical staff and were used to select patient groups that underwent these pathways. An interactive Sankey diagram representing these pathways and a heat map visually representing the weight of each variable were developed for temporal and quantitative illustration. We applied the proposed system to predict unplanned cardiac surgery using clinical pathways determined by sequence pattern mining to select cardiac surgery from complex EHRs to label subject groups and deep learning models. The proposed system aids in the selection of pathway-based patient groups, simplification of labeling, and exploratory the interpretation of the modeling results. The proposed system can help medical staff explore various pathways that patients have undergone and further facilitate the testing of various clinical hypotheses using big data in the medical domain.
Service Quality for Sports and Active Aging in Japanese Community Sports Clubs
Authors: Lin Tzu-Yu , Sakuno Seiichi
Published: November 2020

(1) Background: This study aims to examine the association between service quality for sports and active aging and the impacts on different age cohorts; (2) Methods: This cross-sectional study used a convenience sample of 545 Japanese community sports club (CSC) members over 60 years old, recruited from across eight CSCs in Japan between 2012–2013. A self-administered questionnaire was used to measure the self-reported health status of the elderly, evaluations to CSCs, demographic characteristics, and information on sports programs; (3) Results: The results of multiple logistic regression showed that domains of general evaluation for sports (OR = 1.942 and 95% CI 1.336~2.824), benefits of sports (OR = 1.659 and 95% CI 1.344~2.047), and management in sports (OR = 1.273 and 95% CI 1.011~1.603) were important for club members aged 60–64, the young-old, and the old-old, respectively. With a reduced model for elderly members, stratified analyses showed a significant impact of service quality for sports on active aged people in the benefits and management domains, regardless of sociodemographic information or club participation behavior; (4) Conclusions: The findings suggest that the services encountered in sports are key to promoting health in a community. Service quality in age segmentation should be considered to promote and manage active aging in the future
Single Time-Point Study of the Home Environment and Functionality of Older Adults in Spain
Authors: González Estela , Requena Carmen , Álvarez-Merino Paula
Published: November 2020

Background: The literature favors discussion on socio-spatial conditions at the macro- (city) and micro- (housing) level that promote healthy aging in place. Objectives: (a) Identify the association between physical and social characteristics of the family home and the functional level and quality of life of older people and (b) provide normative data on adequate/inadequate households based on the Home Observation for Measurement of the Environment (HOME) inventory and the Spanish Informant Questionnaire on Cognitive Decline in the Elderly (S-IQCODE) test. Methods: In total, 79 healthy older adults completed the HOME inventory and the Montreal Cognitive Assessment (MoCA), S-IQCODE, Kessler Psychological Distress Scale (K-10) and ICEpop CAPability measure for Older people (ICECAP-O) tests. A regression model, the effect size and the means of the scores of HOME (adequate/inadequate) test and the cognitive level (optimal/normal) were calculated. Results: The regression model discloses that adequate home scores are associated with cognitive level (odds ratio (OR): 0.955, confidence interval (CI)95%: 0.918–0.955); quality of life (OR: 6.542, CI95%: 1.750–24.457), living with other people (OR: 5.753, CI95%: 1.456–22.733) and level of education (OR: 0.252, CI95%: 0.064–0.991). The normative data between HOME and S-IQCODE scores showed a good adjustment (d = 0.70). Conclusion: There is a significant relationship between the physical environment of the home and personal variables (sociodemographic information, quality of life and cognitive functionality). In addition, from this last variable, the normative data of an adequate/inadequate household for an older person have been established.
Fluorescence Assay for the Determination of d-Panthenol Based on Novel Ring-Fused 2-Pyridone Derivative
Authors: Kasprzyk Wiktor , Świergosz Tomasz , Koper Filip
Published: November 2020

Herein, a novel fluorescent method for the determination of d-panthenol (DP) level in solutions with no separate hydrolysis step has been revealed based on the utilization of citric acid (CA) as a derivatizing agent. Consequently, the essential parameters of the derivatization process were established, resulting in the development of sensitive, repeatable, and accurate determination of panthenol. The method was approved, and its usefulness in characterizing the concentration of DP in pharmaceutical formulations and selectivity in the determination of DP were validated. The chemical structure of the new fluorophore formulating in the reaction in DP with CA, i.e., 6-oxo-3,4-dihydro-2H,6H-pyrido[2,1-b][1,3]oxazine-8-carboxylic acid (ODPC), was elucidated using detailed NMR experiments: one-dimensional (1H, 13C) as well as two-dimensional NMR spectra (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC, 1H-15N HSQC, 1H-15N HMBC).
Polar Lipid Fraction E from Sulfolobus acidocaldarius and Dipalmitoylphosphatidylcholine Can Form Stable yet Thermo-Sensitive Tetraether/Diester Hybrid Archaeosomes with Controlled Release Capability
Authors: Ayesa Umme , Chong Parkson Lee-Gau
Published: November 2020

Archaeosomes have drawn increasing attention in recent years as novel nano-carriers for therapeutics. The main obstacle of using archaeosomes for therapeutics delivery has been the lack of an efficient method to trigger the release of entrapped content from the otherwise extremely stable structure. Our present study tackles this long-standing problem. We made hybrid archaeosomes composed of tetraether lipids, called the polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius, and the synthetic diester lipid dipalmitoylphosphatidylcholine (DPPC). Differential polarized phase-modulation and steady-state fluorometry, confocal fluorescence microscopy, zeta potential (ZP) measurements, and biochemical assays were employed to characterize the physical properties and drug behaviors in PLFE/DPPC hybrid archaeosomes in the presence and absence of live cells. We found that PLFE lipids have an ordering effect on fluid DPPC liposomal membranes, which can slow down the release of entrapped drugs, while PLFE provides high negative charges on the outer surface of liposomes, which can increase vesicle stability against coalescence among liposomes or with cells. Furthermore, we found that the zeta potential in hybrid archaeosomes with 30 mol% PLFE and 70 mol% DPPC (designated as PLFE/DPPC(3:7) archaeosomes) undergoes an abrupt increase from −48 mV at 37 °C to −16 mV at 44 °C (termed the ZP transition), which we hypothesize results from DPPC domain melting and PLFE lipid ‘flip-flop’. The anticancer drug doxorubicin (DXO) can be readily incorporated into PLFE/DPPC(3:7) archaeosomes. The rate constant of DXO release from PLFE/DPPC(3:7) archaeosomes into Tris buffer exhibited a sharp increase (~2.5 times), when the temperature was raised from 37 to 42 °C, which is believed to result from the liposomal structural changes associated with the ZP transition. This thermo-induced sharp increase in drug release was not affected by serum proteins as a similar temperature dependence of drug release kinetics was observed in human blood serum. A 15-min pre-incubation of PLFE/DPPC(3:7) archaeosomal DXO with MCF-7 breast cancer cells at 42 °C caused a significant increase in the amount of DXO entering into the nuclei and a considerable increase in the cell’s cytotoxicity under the 37 °C growth temperature. Taken together, our data suggests that PLFE/DPPC(3:7) archaeosomes are stable yet potentially useful thermo-sensitive liposomes wherein the temperature range (from 37 to 42–44 °C) clinically used for mild hyperthermia treatment of tumors can be used to trigger drug release for medical interventions.
Different Sensitivity of Macrophages to Phospholipidosis Induction by Amphiphilic Cationic Drugs
Authors: Öhlinger Kristin , Absenger-Novak Markus , Meindl Claudia , Ober Jennifer , Fröhlich Eleonore
Published: November 2020

Phospholipidosis (PLD), the intracellular accumulation of phospholipids, is an adaptive response to toxic stimuli and serves as an important parameter in the biological assessment of compounds. Cationic amphiphilic drugs are the main inducers of PLD and may impair the function of alveolar macrophages. In vivo and in vitro models are used for PLD screening but the choice of the cellular model may be important because PLD develops in a cell- and species-specific manner. In this study, a panel of different staining (LysoSensor, Acridine Orange, Nile Red, HCS LipidTOX, LysoID) was evaluated in murine (DMBM-2, J774, RAW264.7) and human (THP-1, monocyte-derived macrophages from peripheral blood) cells to identify the most sensitive and easy to analyze staining method and to detect species-specific differences in the reaction pattern. Amiodarone and chloroquine served as inducers of PLD. High content screening was used to compare number, area, and intensity of the staining. Due to the fast staining protocol and the sensitivity of the detection, LysoID proved to be the most suitable dye of the testing. The lower induction of PLD by chloroquine reported in vivo was also seen in this study. THP-1 macrophages, followed by DMBM-2 cells, produced the most similar reaction pattern to human monocyte-derived macrophages.
Epigenetics of Muscle- and Brain-Specific Expression of KLHL Family Genes
Authors: Ehrlich Kenneth C. , Baribault Carl , Ehrlich Melanie
Published: November 2020

KLHL and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in cell function and disease (especially, KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies of epigenetic factors that affect transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in super-enhancers (particularly strong, tissue-specific clusters of enhancers). The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence for an intragenic enhancer in one gene upregulating expression of its neighboring gene, specifically for KLHL40/HHATL and KLHL38/FBXO32 gene pairs. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5′ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3′ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5′ ends of genes in studies of normal and abnormal gene regulation.
Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology
Authors: Souza Felipe da Costa , Ferreira Matthew Thomas , Colquhoun Alison
Published: November 2020

Background: The relationship between glioblastoma (GBM) and fatty acid metabolism could be the key to elucidate more effective therapeutic targets. 15-lipoxygenase-1 (15-LOX), a linolenic acid and arachidonic acid metabolizing enzyme, induces both pro- and antitumorigenic effects in different cancer types. Its role in glioma activity has not yet been clearly described. The objective of this study was to identify the influence of 15-LOX and its metabolites on glioblastoma cell activity. Methods: GBM cell lines were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify 15-LOX metabolites. GBM cells treated with 15-LOX metabolites, 13-hydroxyoctadecadeinoic acid (HODE) and 9-HODE, and two 15-LOX inhibitors (luteolin and nordihydroguaiaretic acid) were also examined. Dose response/viability curves, RT-PCRs, flow cytometry, migration assays, and zymograms were performed to analyze GBM growth, migration, and invasion. Results: Higher quantities of 13-HODE were observed in five GBM cell lines compared to other lipids analyzed. Both 13-HODE and 9-HODE increased cell count in U87MG. 15-LOX inhibition decreased migration and increased cell cycle arrest in the G2/M phase. Conclusion: 15-LOX and its linoleic acid (LA)-derived metabolites exercise a protumorigenic influence on GBM cells in vitro. Elevated endogenous levels of 13-HODE called attention to the relationship between linoleic acid metabolism and GBM cell activity.
Why Vitamin C Could Be an Excellent Complementary Remedy to Conventional Therapies for Breast Cancer
Authors: Codini Michela
Published: November 2020

The most frequent cancer in women is breast cancer, which is a major cause of death. Currently, there are many pharmacological therapies that have made possible the cure and resolution of this tumor. However, these therapies are accompanied by numerous collateral effects that influence the quality of life (QoL) of the patients to varying degrees. For this reason, attention is turning to the use of complementary medicine to improve QoL. In particular, there are increased trials of intravenous injection of vitamin C at high doses to enhance the antitumor activity of drugs and/or decrease their side effects. This review intends to underline the anticancer mechanisms of vitamin C that could explain its efficacy for treating breast cancer, and why the use of vitamin C at high doses could help patients with breast cancer to enhance the efficacy of pharmacological therapies and/or decrease their side effects.
A Novel Inhibitor of Carbonic Anhydrases Prevents Hypoxia-Induced TNBC Cell Plasticity
Authors: Sarnella Annachiara , D’Avino Giuliana , Hill Billy Samuel , Alterio Vincenzo , Winum Jean-Yves , Supuran Claudiu T. , De Simone Giuseppina , Zannetti Antonella
Published: November 2020

Cell plasticity is the ability that cells have to modify their phenotype, adapting to the environment. Cancer progression is under the strict control of the the tumor microenvironment that strongly determines its success by regulating the behavioral changes of tumor cells. The cross-talk between cancer and stromal cells and the interactions with the extracellular matrix, hypoxia and acidosis contribute to trigger a new tumor cell identity and to enhance tumor heterogeneity and metastatic spread. In highly aggressive triple-negative breast cancer, tumor cells show a significant capability to change their phenotype under the pressure of the hypoxic microenvironment. In this study, we investigated whether targeting the hypoxia-induced protein carbonic anhydrase IX (CA IX) could reduce triple-negative breast cancer (TNBC) cell phenotypic switching involved in processes associated with poor prognosis such as vascular mimicry (VM) and cancer stem cells (CSCs). The treatment of two TNBC cell lines (BT-549 and MDA-MB-231) with a specific CA IX siRNA or with a novel inhibitor of carbonic anhydrases (RC44) severely impaired their ability to form a vascular-like network and mammospheres and reduced their metastatic potential. In addition, the RC44 inhibitor was able to hamper the signal pathways involved in triggering VM and CSC formation. These results demonstrate that targeting hypoxia-induced cell plasticity through CA IX inhibition could be a new opportunity to selectively reduce VM and CSCs, thus improving the efficiency of existing therapies in TNBC.
High Stroma T-Cell Infiltration is Associated with Better Survival in Stage pT1 Bladder Cancer
Authors: Hülsen Sabine , Lippolis Eleonora , Ferrazzi Fulvia , Otto Wolfgang , Distel Luitpold , Fietkau Rainer , Denzinger Stefan , Breyer Johannes , Burger Maximilian , Bertz Simone , Eckstein Markus , Ebner Annette , Hartmann Arndt , Geppert Carol-I.
Published: November 2020

Stage pT1 bladder cancer (BC) shows highly diverse outcomes. Predictive markers are required to stratify patients for personalized treatment. The present study aimed to validate immune response quantification as a prognostic marker. Patients with pT1 BC (n = 167) treated by transurethral resection of the bladder (TURB) were enrolled. Formaldehyde-fixed paraffin-embedded material was stained for CD3 and CD8. Corresponding T cells were counted in three regions with the highest immune response. Numbers of tertiary lymphoid structures (TLS) and lymphocyte aggregates (LA) were quantified. High CD3+ stroma T-cell infiltration was associated with improved survival (p = 0.045), especially in the G3 subgroup (p = 0.01). Cluster with higher immune response showed less recurrence (p = 0.034) and favorable overall survival (OS) (p = 0.019). In contrast, higher CD3+ and CD8+ tumor T-cell infiltration seemed to have a negative impact on prognosis. TLS and LA were more frequently observed in G3 tumors, indicating an increased anti-tumoral immune response. We proved the role of immune cell infiltration and showed that higher infiltration numbers of CD3+ (not CD8+) lymphocytes in the stroma are associated with favorable outcome. Immune cell quantification could be used as a marker to help stratify patients’ risk and therefore, to optimize patients’ management and follow-up examination as well as possible therapies.
Ketamine and Calcium Signaling—A Crosstalk for Neuronal Physiology and Pathology
Authors: Lisek Malwina , Zylinska Ludmila , Boczek Tomasz
Published: November 2020

Ketamine is a non-competitive antagonist of NMDA (N-methyl-D-aspartate) receptor, which has been in clinical practice for over a half century. Despite recent data suggesting its harmful side effects, such as neuronal loss, synapse dysfunction or disturbed neural network formation, the drug is still applied in veterinary medicine and specialist anesthesia. Several lines of evidence indicate that structural and functional abnormalities in the nervous system caused by ketamine are crosslinked with the imbalanced activity of multiple Ca2+-regulated signaling pathways. Due to its ubiquitous nature, Ca2+ is also frequently located in the center of ketamine action, although the precise mechanisms underlying drug’s negative or therapeutic properties remain mysterious for the large part. This review seeks to delineate the relationship between ketamine-triggered imbalance in Ca2+ homeostasis and functional consequences for downstream processes regulating key aspects of neuronal function.
Molecular Mechanisms of “Antiphospholipid Antibodies” and Their Paradoxical Role in the Pathogenesis of “Seronegative APS”
Authors: Misasi Roberta , Longo Agostina , Recalchi Serena , Caissutti Daniela , Riitano Gloria , Manganelli Valeria , Garofalo Tina , Sorice Maurizio , Capozzi Antonella
Published: November 2020

Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL). In some cases, patients with a clinical profile indicative of APS (thrombosis, recurrent miscarriages or fetal loss), who are persistently negative for conventional laboratory diagnostic criteria, are classified as “seronegative” APS patients (SN-APS). Several findings suggest that aPL, which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), may contribute to thrombotic diathesis by interfering with hemostasis. Despite the strong association between aPL and thrombosis, the exact pathogenic mechanisms underlying thrombotic events and pregnancy morbidity in APS have not yet been fully elucidated and multiple mechanisms may be involved. Furthermore, in many SN-APS patients, it is possible to demonstrate the presence of unconventional aPL (“non-criteria” aPL) or to detect aPL with alternative laboratory methods. These findings allowed the scientists to study the pathogenic mechanism of SN-APS. This review is focused on the evidence showing that these antibodies may play a functional role in the signal transduction pathway(s) leading to thrombosis and pregnancy morbidity in SN-APS. A better comprehension of the molecular mechanisms triggered by aPL may drive development of potential therapeutic strategies in APS patients.