bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Maximum Amount of Orthodontic Force for Dental Pulp and Apical Neuro-Vascular Bundle in Intact and Reduced Periodontium on Bicuspids (Part II)
Authors: Moga Radu Andrei , Olteanu Cristian Doru , Botez Mircea , Buru Stefan Marius
Published: January 2023

This study examines 0.6 N–4.8 N as the maximum orthodontic force to be applied to dental pulp and apical NVB on intact and 1–8 mm reduced periodontal-ligament (PDL), in connection with movement and ischemic, necrotic and resorptive risk. In addition, it examines whether the Tresca finite-element-analysis (FEA) criterion is more adequate for the examination of dental pulp and its apical NVB. Eighty-one (nine patients, with nine models for each patient) anatomically correct models of the periodontium, with the second lower-premolar reconstructed with its apical NVB and dental pulp were assembled, based on X-ray CBCT (cone-beam-computed-tomography) examinations and subjected to 0.6 N, 1.2 N, 2.4 N and 4.8 N of intrusion, extrusion, translation, rotation, and tipping. The Tresca failure criterion was applied, and the shear stress was assessed. Forces of 0.6 N, 1.2 N, and 2.4 N had negligible effects on apical NVB and dental pulp up to 8 mm of periodontal breakdown. A force of 4.8 N was safely applied to apical NVB on the intact periodontium only. Rotation and tipping seemed to be the most invasive movements for the apical NVB. For the dental pulp, only the translation and rotation movements seemed to display a particular risk of ischemia, necrosis, and internal orthodontic-resorption for both coronal (0–8 mm of loss) and radicular pulp (4–8 mm of loss), despite the amount of stress being lower than the MHP. The Tresca failure criterion seems more suitable than other criteria for apical NVB and dental pulp.
Exploring Urban Green Space Optimization of the Urban Walking Life Circle in Fuzhou, China
Authors: Xie Huili , Wang Xinke , Hu Xiaoting , Shi Zhiyong , Lin Hong , Xie Xiangqun , Chen Lingxiu , Dai Hongxia , Zhang Jiao , Xu Mengjie , Liu Xingzhao
Published: January 2023

The spatial distribution of urban green spaces (UGS) is closely related to the health of residents and the ecological pattern of cities. Exploring the equity of UGSs plays an important role in urban planning and also provides guidance for urban development. Taking the main urban area of Fuzhou City as an example, this study uses network big data and census data to pinpoint the population demand, evaluates the accessibility and equity of UGS within the basic living circle, neighborhood living circle and daily living circle of residents at the scale of residential and sub-districts. Based on the G2SFCA model, we also quantify the actual effective UGS’s service capacity. Then, using the scale and travel range as the entry point, we further discuss the similarities and differences under different scales and different travel ranges. Finally, optimization strategies are proposed for the construction status. The results show that: (1) The spatial allocation of urban green space resources varies significantly, and there is a serious inequity in the spatial distribution of urban green space under pedestrian conditions; (2) The results of UGS accessibility, equity, and service capacity in Fuzhou at both residential and sub-district scales are consistent; (3) Urban construction should be multi-level overall planning, combined with local economic and social development factors in accordance with local conditions to take measures. The results of the study can provide a scientific reference for the optimization of the spatial distribution of UGS.
Breakfast Quality and Insulin Resistance in Spanish Schoolchildren: A Cross-Sectional Study
Authors: Salas-González María Dolores , Lozano-Estevan María del Carmen , Aparicio Aránzazu , Bermejo Laura M. , Loria-Kohen Viviana , Ortega Rosa M. , López-Sobaler Ana M.
Published: January 2023

Background: Breakfast has traditionally been considered one of the most important meals of the day; however, there is little evidence for the influence of breakfast quality and insulin resistance (IR). This study aimed to assess the quality of breakfast in a group of schoolchildren, and its association with IR. Methods: A cross-sectional study with 852 children (8–13 years) was carried out. Fasting plasma glucose, insulin and anthropometric parameters were measured. A three-day dietary record was used to assess their diet and to calculate the Breakfast Quality Index (BQI). The sample was divided into tertiles according to the BQI (tertile 3: better breakfast quality). The homeostatic model was used to assess insulin resistance (HOMA-IR), and IR was defined as HOMA-IR > 3.16. Results: The prevalence of IR was 5.2%. The mean BQI score was 4.50 ± 1.25, and boys had lower scores than girls. Children in the BQI tertile 3 had a better global diet quality. In boys, being in the BQI tertile 3 was associated with a lower risk of IR (OR [95% CI]: 0.10 [0.01–0.77], p < 0.05). Conclusions: A higher-quality breakfast was associated with better overall diet quality and a lower risk of IR, especially in boys.
Cognitive Analyses for Interface Design Using Dual N-Back Tasks for Mental Workload (MWL) Evaluation
Authors: Arana-De las Casas Nancy Ivette , De la Riva-Rodríguez Jorge , Maldonado-Macías Aide Aracely , Sáenz-Zamarrón David
Published: January 2023

In the manufacturing environments of today, human–machine systems are constituted with complex and advanced technology, which demands workers’ considerable mental workload. This work aims to design and evaluate a Graphical User Interface developed to induce mental workload based on Dual N-Back tasks for further analysis of human performance. This study’s contribution lies in developing proper cognitive analyses of the graphical user interface, identifying human error when the Dual N-Back tasks are presented in an interface, and seeking better user–system interaction. Hierarchical task analysis and the Task Analysis Method for Error Identification were used for the cognitive analysis. Ten subjects participated voluntarily in the study, answering the NASA-TLX questionnaire at the end of the task. The NASA-TLX results determined the subjective participants’ mental workload proving that the subjects were induced to different levels of mental workload (Low, Medium, and High) based on the ANOVA statistical results using the mean scores obtained and cognitive analysis identified redesign opportunities for graphical user interface improvement.
Levels of Toxic and Essential Elements and Associated Factors in the Hair of Japanese Young Children
Authors: Kusanagi Emiko , Takamura Hitoshi , Hoshi Nobuko , Chen Shing-Jen , Adachi Mayumi
Published: January 2023

There is growing concern regarding the effects of toxic element exposure on the development of children. However, little is known about the level of toxic elements exposure in Japanese children. The purpose of this study was to assess the concentrations of multiple elements (aluminum, cadmium, lead, calcium, copper, iron, magnesium, sodium, zinc) in the hair of 118 Japanese young children and to explore the factors associated with their element levels. The element concentration was analyzed by ICP-MS, and children’s food and water intake were assessed by the questionnaire. Results showed that there were no large differences between the level of elements in the hair of Japanese children and those of children in other developed countries. Girls had significantly higher levels of aluminum, copper, and iron (p = 0.000, 0.014, and 0.013, respectively), and boys had a higher level of sodium (p = 0.006). The levels of calcium, iron, magnesium, and sodium in nursery school children were significantly higher than those in kindergarten children (p = 0.024, 0.001, 0.046, and 0.029, respectively). Multiple regression analyses with controlling the confounding variables showed significant negative associations of frequency of yogurt intake with aluminum and lead levels (p = 0.015 and 0.037, respectively). When the children were divided into three groups based on the frequency of yoghurt consumption, viz. L (≤once a week), M (2 or 3 times a week), and H (≥4 to 6 times a week) group, the mean aluminum concentration (µg/g) in the L, M, and H groups was 11.06, 10.13, and 6.85, while the mean lead concentration (µg/g) was 1.76, 1.70, and 0.87, respectively. Our results suggested the validity of hair element concentrations as an exposure measure of essential elements and frequent yogurt intake as a viable measure for protecting children from toxic elements. However, these findings will need to be confirmed in more detailed studies with larger sample sizes in the future.
Risk Factors Associated with Children Receiving Treatment at Emergency Dental Clinics: A Case-Control Study
Authors: Sabbagh Heba Jafar , Albeladi Nuha Hamdi , Altabsh Nadeen Zouhair , Bamashmous Nada Othman
Published: January 2023

(1) Background: The process of managing children at the emergency dental clinic (ER-C) is a difficult challenge. This matched case-control study assessed risk factors associated with children visiting the ER-C compared to visits at the regular dental clinic (RD-C). (2) Methods: The participants included 421 children aged three to 12 years who were recruited at the ER-C (cases) and RD-C (controls) at King Abdulaziz University Dental Hospital, with each group matched for gender and age. A data-collection form was developed and validated in both Arabic and English, containing the following four sections: DMFT/dmft index, Frankl’s behaviour rating scale, Dental Neglect Scale, and Dental Care Barriers questionnaire. (3) Results: The ER-C (vs RD-C) group showed significantly more uncooperative behaviour (p = 0.002), a higher total mean dental neglect score (p = 0.003), and a higher dental barrier score (p < 0.001). Binary regression analysis showed that those making their first visit (AOR: 2.65, p < 0.001) and with higher dental barriers (AOR: 1.121, p < 0.001) were statistically significantly more associated with ER-C visitation. (4) Conclusion: These findings suggest that children who visit the ER-C are more prone to dental care barriers, uncooperative behaviour, and dental neglect, thus highlighting the importance of encouraging and planning their attendance to ensure optimal dental care.
Stimulus-Organism-Response Framework: Is the Perceived Outstanding Universal Value Attractiveness of Tourists Beneficial to World Heritage Site Conservation?
Authors: Nian Sifeng , Li Donghe , Zhang Jie , Lu Song , Zhang Xiaowan
Published: January 2023

Tourists have been attracted to world heritage sites (WHSs) by their Outstanding Universal Value (OUV). In view of the Stimulus-Organism-Response (S-O-R) framework and the theory of attitude and behavior, by employing 563 tourist samples from Mount Sanqingshan National Park, and using structural equation modeling, we examine tourist behavioral intention for heritage conservation, and the following conclusions were drawn: (1) the S-O-R theory revealed the behavioral intentions of tourists to protect WHSs; (2) as a stimulus, tourists’ value perception and destination attachment were positively affected by the OUV attractiveness, and their perceived value had a positive influence on heritage conservation, although the hypothesis of destination attachment to heritage conservation was not supported; (3) heritage-conservation education and knowledge positively influenced tourists’ behavioral intentions towards heritage protection, and tourists’ heritage protection attitude had a positive influence on their behavioral intention; and (4) a framework of the influence mechanism for tourists’ heritage conservation based on the S-O-R theory was proposed, while tourists’ cognitive and affective attitudes impacted on heritage protection intention which, in turn, further enhanced the tourists’ perception of the OUV. Conclusively, the measures and implications were proposed for improving conservation and management of WHSs, in particular to achieve the sustainable development of the tourist industry and world heritage sites.
An Integrated Approach to Workplace Mental Health: A Scoping Review of Instruments That Can Assist Organizations with Implementation
Authors: Nebbs Adam , Martin Angela , Neil Amanda , Dawkins Sarah , Roydhouse Jessica
Published: January 2023

This study aimed to identify instruments that may assist organizations with implementing an integrated approach to workplace mental health using three activities from the knowledge to action (KTA) framework. A scoping review of published and grey literature, supported by stakeholder (business end-user and researcher) consultation, identified work-specific instruments that were relevant to at least one of the three domains of an integrated approach to workplace mental health: ‘prevent harm’, ‘promote the positive’, and ‘respond to problems’. A total of 207 instruments were located, and 109 instruments met eligibility criteria. 10 instruments were located that were relevant to multiple domains, however most instruments (n = 72) were relevant to the ‘prevent harm’ domain. Instruments relevant to the ‘promote the positive’ (n = 14) and ‘respond to problems’ (n = 13) domains were limited. Most instruments found were suitable for the ‘monitor, review and improve’ KTA activity. Further development of instruments that can assist with ‘promote the positive’ and ‘respond to problems’ strategies are required, specifically those instruments that can assist organizations with the ‘identify gaps and opportunities’ and ‘identify priorities and design new/enhanced interventions’ KTA activities.
A Retrospective Longitudinal Analysis of Mental Health Admissions: Measuring the Fallout of the Pandemic
Authors: Warwicker Sean , Sant Denise , Richard Adrian , Cutajar Jake , Bellizzi Annalise , Micallef Gertrude , Refalo Daniel , Camilleri Liberato , Grech Anton
Published: January 2023

Background: In this research article, we review the infrequently considered long-term impact of the pandemic on inpatient mental health, by reviewing the clinical parameters of all psychiatric admissions to Mount Carmel Hospital, our region’s main psychiatric healthcare facility, from 2019–2021. Methods: 4292 patients were admitted during the research period of this retrospective longitudinal analysis. Taking 2019 as the pre-COVID reference year, we compared mean monthly admissions from 2020 and 2021, looking at patient demographics, status under the Mental Health Act, diagnosis, and self-injurious behaviour. Results: While the pandemic was reflected in a moderate increase in mean monthly presentations with suicidal ideation and suicidal self-injury, presentations in 2020 otherwise remained largely stable. This contrasted with a surge in presentations in 2021 with mood disorders, schizophrenia, anxiety, personality disorders, and autism spectrum disorders. Furthermore, presentations involving self-injurious behaviour continued to grow. Involuntary admissions also increased significantly in 2021. Conclusions: This paper highlights the pernicious long-term impact of the pandemic on mental health presentations, demonstrated by an increase in hospital admissions and more serious presentations. These findings should be considered in the guidance for responses to any future pandemic, giving attention to the evidence of the impact of restrictive measures on mental health.
Computer-Aided Greenery Design—Prototype Green Structure Improving Human Health in Urban Ecosystem
Authors: Sędzicki Dominik , Cudzik Jan , Nyka Lucyna
Published: January 2023

Increasing population and urbanization, with climate change consequences, such as rising temperatures, influence public health and well-being. The search to improve the quality of life in cities becomes one of the priority objectives. A solution can be found in the role of greenery in an urban environment and its impact on human health. This opens a path toward experimentation on microclimate green structures that can be inserted into dense urban spaces providing human and environmental benefits. The article proposes an automated greenery design method combined with rapid prototyping for such interventions. A theoretical analysis of the problem preceded the introduction of the method. The research process was developed in accordance with the main objectives of the CDIO framework (Conceive, Design, Implement, and Operate) with the SiL (Software in the Loop) and HiL (Hardware in the Loop) methods. Moreover, the applied test model allows for complex evaluation in order to ensure quality and directions for further development.
The Pandemic-Related Factors Associated with Emergency Department Visits in Portugal throughout Two Years of the Pandemic: A Retrospective Population-Based Study
Authors: Kinaan Walaa , Soares Patrícia , Rocha João Victor , Boto Paulo , Santana Rui , Lopes Sílvia
Published: January 2023

The COVID-19 pandemic has affected the use of emergency departments (ED) worldwide. This study identifies the pandemic-related factors associated with the number of ED visits in mainland Portugal and each of its regions. We collected data on ED visits from March 2020 to March 2022. Data on incidence, vaccination, mobility, containment index, and Google search volume were retrieved from open online sources at different time points. We fitted a quasi-Poisson generalized linear regression model, and each variable was modeled separately and adjusted for time and month. There was a positive ED trend throughout the two years of the pandemic in mainland Portugal and each of its regions. In the mainland, during months with high workplace mobility, there were 10.5% more ED visits compared to months with average mobility. ED visits decreased in months with low mobility for retail and recreation, groceries and pharmacies, and transit compared to months of medium mobility. Portugal saw a reduction in ED utilization during the pandemic period, but with a positive trend from March 2020 to March 2022. The change in the population’s behavior of seeking the ED throughout the pandemic might be associated with mobility, incidence, and pandemic fatigue.
A Cross-Sectional Analysis of Intimacy Problems, Stress Levels, and Couple Satisfaction among Women with Thrombophilia Affected by Recurrent Pregnancy Loss
Authors: Nitu Razvan , Neamtu Radu , Iordache Olivera , Stelea Lavinia , Dahma George , Sacarin Geanina , Socol George , Boarta Aris , Silaghi Carmen , Puichita Daiana , Diaconu Mircea Mihai
Published: January 2023

Recurrent pregnancy loss (RPL) is one of the most challenging and difficult areas of reproductive treatment due to the immense emotional suffering inflicted on families and couples affected by RPL. As a result, it is predicted that couples experiencing recurrent pregnancy loss would have an increase in marital problems, stress levels, and anxiety, preventing them from achieving their family goals. The current cross-sectional study aimed to target pregnant women with thrombophilia with a history of RPL to observe their intimacy problems, stress levels, and couple satisfaction by completing a series of digital questionnaires. These patients were considered as the reference group, while the control group was formed by other women with thrombophilia and a history of RPL who eventually achieved pregnancy and gave birth. A total of 238 complete questionnaires were recorded (157 in the reference group and 81 in the control group). It was observed that women in the reference group who did not give birth had a significantly higher proportion of three or more pregnancy attempts (54.1% vs. 39.5%) and a significantly higher proportion of three more pregnancy losses (68.8% vs. 55.6%). It was observed that patients in the reference group were more likely to be emotion-oriented (42.7% vs. 27.2%). Also, women in the reference group had higher levels of dissatisfaction and lower levels of self-acceptance, pleasure, and marital quality scores. The total SII and DSCS scores were significantly lower than women with thrombophilia with a history of RPL who eventually gave birth. Women from the reference group had significantly greater intimacy problems and stress levels while having lower openness scores and self-esteem scores than women in the control group. It is possible that women with thrombophilia and recurrent pregnancy loss are more dissatisfied with their marriages than those who subsequently had one child. Since the financial status of those who achieved pregnancy was observed to be higher, it is likely that they achieved pregnancy by ART interventions, as they reported in questionnaires. It is important to target families afflicted by thrombophilia and other reasons for infertility to ease their access to ART therapies. By achieving their objectives, affected families will minimize dissatisfaction, divorce rates, and stress.
Responses to Wildfire and Prescribed Fire Smoke: A Survey of a Medically Vulnerable Adult Population in the Wildland-Urban Interface, Mariposa County, California
Authors: Hoshiko Sumi , Buckman Joseph R. , Jones Caitlin G. , Yeomans Kirstin R. , Mello Austin , Thilakaratne Ruwan , Sergienko Eric , Allen Kristina , Bello Lisa , Rappold Ana G.
Published: January 2023

California plans to substantially increase the use of prescribed fire to reduce risk of catastrophic wildfires. Although for a beneficial purpose, prescribed fire smoke may still pose a health concern, especially among sensitive populations. We sought to understand community health experience, adaptive capacity, and attitudes regarding wildland and prescribed fire smoke to inform public health guidance. We conducted a cross-sectional survey of medically vulnerable persons in a rural, high fire risk county (N = 106, 76% > 65 years) regarding wildfire and prescribed smoke health effects; health protective actions; information needs; and support for fire management policies. Qualitative comments were reviewed for context and emerging themes. More than half (58%) of participants reported health impacts from wildfire smoke; 26% experienced impacts from prescribed fire smoke. Participants expressed strong support for prescribed fire, although also concerns about safety and smoke. Respondents reported taking actions to reduce smoke exposure (average 5 actions taken per person), but many (47%) lacked confidence that they could successfully protect their health. Persons who were satisfied with the information received tended to be more confident in their ability to protect their health compared to those who were not satisfied (61% vs. 35%). More information was desired on many topics, including notifications about prescribed fire, health protection and exposure reduction. As California expands use of prescribed fire, the need for effective health protective communication regarding smoke is increasingly vital. We recommend seeking solutions that strengthen community resilience and address equity for vulnerable populations.
It Is Not the Virus Exposure: Differentiating Job Demands and Resources That Account for Distress during the COVID-19 Pandemic among Health Sector Workers
Authors: Dominguez-Espinosa Alejandra del Carmen , Fontaine Johnny R. J.
Published: January 2023

A cross-sectional study of 3860 health-sector workers across two data collections was conducted to identify the predictive power of different job demands and job resources during the COVID-19 pandemic based on four indicators of distress (COVID-19 traumatic stress, burnout, generalised anxiety, and depression) among health-sector workers. Exploratory and confirmatory factor analyses, measurement invariance checks, and structural equation models were used to evaluate the dimensionality and the effect of the job demands and resources on distress indictors. The identified job demands were workload, confinement, loss, and virus exposure, while the identified job resources were self-efficacy, momentary recuperation, and meaning making. Loss and workload predicted the distress indicators best, while confinement and virus exposure mainly predicted COVID-19 traumatic stress and were less important for the other distress outcomes. Self-efficacy and meaning making negatively predicted distress, while momentary recuperation, controlled for the other demands and resources, was positively related to the distress indicators. Of the typical pandemic-related demands and resources, the experience of loss due to COVID-19 infection was the most important predictor of distress outcomes. Confinement, and especially the awareness of virus exposure, were far less important predictors.
Recommendations from Latinx Trans and Non-Binary Individuals to Promote Cancer Prevention in Puerto Rico and Florida
Authors: Rivera-Custodio Joshua J. , Soto-Sanchez Ana V. , Alvarado-Cardona Elvin O. , Moreta-Ávila Fabian , Silva-Reteguis Julian , Velez-Perez Erik , Jiménez-Ricaurte Coral , Rivera-Segarra Eliut , Rodríguez-Madera Sheilla L. , Ramos-Pibernus Alixida
Published: January 2023

Latinx trans and non-binary individuals (LTNB) face increased cancer-related health disparities. Studies evidence how barriers at the individual, provider and organizational levels drive cancer disparities among LTNB individuals. These barriers increase the emotional discomfort associated with testing and disengagement from cancer prevention efforts. Moreover, there are no guidelines or interventions that address cancer prevention specifically among LTNB individuals. There is a need to develop interventions informed by the LTNB communities to promote cancer prevention and screening. The study aims to describe the recommendations provided by LTNB individuals to foster cancer screening and prevention in the communities residing in Puerto Rico and Florida. We conducted two online focus groups with a total of 15 LTNB participants. Participants were recruited using non-probabilistic purposive sampling. We used rapid-qualitative analysis for data interpretation. Findings are gathered in three main themes: (1) recommendations for promoting cancer prevention screening among providers; (2) specific recommendations to promote cancer screening among LTBN individuals; and (3) recommendations on delivery formats to foster cancer prevention. These results evidence the need and feasibility of developing community informed tailored interventions targeting cancer screening and preventative care to reduce cancer-related health disparities among the LTNB population.
The Impact of a Large-Scale Social and Behavior Change Communication Intervention in the Lake Zone Region of Tanzania on Knowledge, Attitudes, and Practices Related to Stunting Prevention
Authors: Dearden Kirk , Mulokozi Generose , Linehan Mary , Cherian Dennis , Torres Scott , West Joshua , Crookston Benjamin , Hall Cougar
Published: January 2023

Background: Large-scale social and behavioral change communication (SBCC) approaches can be beneficial to achieve improvements in knowledge, attitudes, and practices (KAP). Addressing Stunting in Tanzania Early (ASTUTE) included a significant SBCC component and targeted precursors to stunting including KAP related to maternal and child health, antenatal care, WASH, childhood development, and male involvement. METHODS: Baseline, midline, and endline surveys were conducted for a total of 14,996 female caregivers and 6726 male heads of household in the Lake Zone region of Tanzania. Regression analyses were used to estimate differences in KAP from baseline to midline and endline. Results: Women’s knowledge of handwashing and infant/child feeding practices, and attitudes related to male involvement, consistently improved from baseline to midline and baseline to endline. Women’s practices related to antenatal care, breastfeeding, and early child development improved from baseline to midline and baseline to endline. Improvements in KAP among male heads of household were varied across indicators with consistent improvement in practices related to child feeding practices from baseline to midline and baseline to endline. Conclusion: Many changes in KAP were observed from baseline to midline and baseline to endline and corresponded with SBCC programming in the region. These results provide support for the value of large SBCC interventions. Public health efforts in settings such as Tanzania may benefit from adopting these approaches.
Digital Case Manager—A Data-Driven Tool to Support Family Caregivers with Initial Guidance
Authors: Wunderlich Paul , Wiegräbe Frauke , Dörksen Helene
Published: January 2023

Due to the demographic aging of society, the demand for skilled caregiving is increasing. However, the already existing shortage of professional caregivers will exacerbate in the future. As a result, family caregivers must shoulder a heavier share of the care burden. To ease the burden and promote a better work-life balance, we developed the Digital Case Manager. This tool uses machine learning algorithms to learn the relationship between a care situation and the next care steps and helps family caregivers balance their professional and private lives so that they are able to continue caring for their family members without sacrificing their own jobs and personal ambitions. The data for the machine learning model are generated by means of a questionnaire based on professional assessment instruments. We implemented a proof-of-concept of the Digital Case Manager and initial tests show promising results. It offers a quick and easy-to-use tool for family caregivers in the early stages of a care situation.
Zinc- and Copper-Doped Mesoporous Borate Bioactive Glasses: Promising Additives for Potential Use in Skin Wound Healing Applications
Authors: Kermani Farzad , Nazarnezhad Simin , Mollaei Zahra , Mollazadeh Sahar , Ebrahimzadeh-Bideskan Alireza , Askari Vahid Reza , Oskuee Reza Kazemi , Moradi Ali , Hosseini Seyede Atefe , Azari Zoleikha , Baino Francesco , Kargozar Saeid
Published: January 2023

In this study, zinc (Zn)- and copper (Cu)-doped 13-93B3 borate mesoporous bioactive glasses (MBGs) were successfully synthesized using nitrate precursors in the presence of Pluronic P123. We benefited from computational approaches for predicting and confirming the experimental findings. The changes in the dynamic surface tension (SFT) of simulated body fluid (SBF) were investigated using the Du Noüy ring method to shed light on the mineralization process of hydroxyapatite (HAp) on the glass surface. The obtained MBGs were in a glassy state before incubation in SBF. The formation of an apatite-like layer on the SBF-incubated borate glasses was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The incorporation of Zn and Cu into the basic composition of 13-93B3 glass led to changes in the glass transition temperature (Tg) (773 to 556 °C), particle size (373 to 64 nm), zeta potential (−12 to −26 mV), and specific surface area (SBET) (54 to 123 m2/g). Based on the K-means algorithm and chi-square automatic interaction detection (CHAID) tree, we found that the SFT of SBF is an important factor for the prediction and confirmation of the HAp mineralization process on the glasses. Furthermore, we proposed a simple calculation, based on SFT variation, to quantify the bioactivity of MBGs. The doped and dopant-free borate MBGs could enhance the proliferation of mouse fibroblast L929 cells at a concentration of 0.5 mg/mL. These glasses also induced very low hemolysis (<5%), confirming good compatibility with red blood cells. The results of the antibacterial test revealed that all the samples could significantly decrease the viability of Pseudomonas aeruginosa. In summary, we showed that Cu-/Zn-doped borate MBGs can be fabricated using a cost-effective method and also show promise for wound healing/skin tissue engineering applications, as especially supported by the cell test with fibroblasts, good compatibility with blood, and antibacterial properties.
Comparative Zymocidial Effect of Three Different Killer Toxins against Brettanomyces bruxellensis Spoilage Yeasts
Authors: Agarbati Alice , Ciani Maurizio , Esin Semih , Agnolucci Monica , Marcheggiani Fabio , Tiano Luca , Comitini Francesca
Published: January 2023

Three killer toxins that were previously investigated, one excreted by Kluyveromyces wickerhamii and two by different strains of Wickerhamomyces anomalus, were produced at the pilot scale, lyophilized and characterized, and the formulates were assessed for their zymocidial effect against Brettanomyces bruxellensis spoilage yeast. A comparative analysis allowed the evaluation of the minimum inhibitory concentration (MIC) against a sensitive strain. Fungicidal and fungistatic concentrations were used to evaluate the cytocidal effect using a cytofluorimetric approach that confirmed the lethal effect of all lyophilized formulates against B. bruxellensis spoilage yeasts. Moreover, the potential killer toxins’ cytotoxicity against human intestinal cells (Caco-2) were evaluated to exclude any possible negative effect on the consumers. Finally, the effective lethal effect of all three lyophilized killer toxins toward B. bruxellensis sensitive strain were tested. The results indicated that all of them acted without dangerous effects on the human epithelial cells, opening the way for their possible commercial application. In particular, D15 showed the lowest MIC and the highest activity, was evaluated also in wine, revealing a strong reduction of Brettamonyces yeast growth and, at the same time, a control of ethyl phenols production.
Emerging Perspectives on the Rare Tubulopathy Dent Disease: Is Glomerular Damage a Direct Consequence of ClC-5 Dysfunction?
Authors: Priante Giovanna , Ceol Monica , Gianesello Lisa , Bizzotto Dario , Braghetta Paola , Calò Lorenzo Arcangelo , Del Prete Dorella , Anglani Franca
Published: January 2023

Dent disease (DD1) is a rare tubulopathy caused by mutations in the CLCN5 gene. Glomerulosclerosis was recently reported in DD1 patients and ClC-5 protein was shown to be expressed in human podocytes. Nephrin and actin cytoskeleton play a key role for podocyte functions and podocyte endocytosis seems to be crucial for slit diaphragm regulation. The aim of this study was to analyze whether ClC-5 loss in podocytes might be a direct consequence of the glomerular damage in DD1 patients. Three DD1 kidney biopsies presenting focal global glomerulosclerosis and four control biopsies were analyzed by immunofluorescence (IF) for nephrin and podocalyxin, and by immunohistochemistry (IHC) for ClC-5. ClC-5 resulted as down-regulated in DD1 vs. control (CTRL) biopsies in both tubular and glomerular compartments (p < 0.01). A significant down-regulation of nephrin (p < 0.01) in DD1 vs. CTRL was demonstrated. CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/Caspase9) gene editing of CLCN5 in conditionally immortalized human podocytes was used to obtain clones with the stop codon mutation p.(R34Efs*14). We showed that ClC-5 and nephrin expression, analyzed by quantitative Reverse Transcription/Polymerase Chain Reaction (qRT/PCR) and In-Cell Western (ICW), was significantly downregulated in mutant clones compared to the wild type ones. In addition, F-actin staining with fluorescent phalloidin revealed actin derangements. Our results indicate that ClC-5 loss might alter podocyte function either through cytoskeleton disorganization or through impairment of nephrin recycling.
Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model
Authors: Thangavel Hariprasad , Dhanyalayam Dhanya , Lizardo Kezia , Oswal Neelam , Dolgov Enriko , Perlin David S. , Nagajyothi Jyothi F.
Published: January 2023

The coronavirus disease (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 has had a catastrophic effect globally causing millions of deaths worldwide and causing long-lasting health complications in COVID-19 survivors. Recent studies including ours have highlighted that adipose tissue can act as a reservoir where SARS-CoV-2 can persist and cause long-term health problems. Here, we evaluated the effect of SARS-CoV-2 infection on adipose tissue physiology and the pathogenesis of fat loss in a murine COVID-19 model using humanized angiotensin-converting enzyme 2 (hACE2) mice. Since epidemiological studies reported a higher mortality rate of COVID-19 in males than in females, we examined hACE2 mice of both sexes and performed a comparative analysis. Our study revealed for the first time that: (a) viral loads in adipose tissue and the lungs differ between males and females in hACE2 mice; (b) an inverse relationship exists between the viral loads in the lungs and adipose tissue, and it differs between males and females; and (c) CoV-2 infection alters immune signaling and cell death signaling differently in SARS-CoV-2 infected male and female mice. Overall, our data suggest that adipose tissue and loss of fat cells could play important roles in determining susceptibility to CoV-2 infection in a sex-dependent manner.
Screening System of Cannabis sativa Extracts Based on Their Mitochondrial Safety Profile Using Cytochrome c Oxidase Activity as a Biomarker
Authors: Noskova Ekaterina , Fernández Roberto , García Javier , Ochoa Eneko , Domínguez-Fernández Celtia , Adell Albert , Laso Antonio , Andrés Maria Fe , González-Coloma Azucena , Astigarraga Egoitz , Barreda-Gómez Gabriel
Published: January 2023

The development of Cannabis sativa strains with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) content is a growing field of research, both for medical and recreational use. However, the mechanisms behind clinical actions of cannabinoids are still under investigation, although there is growing evidence that mitochondria play an important role in many of them. Numerous studies have described that cannabinoids modulate mitochondrial activity both through activation of mitochondrial cannabinoid receptors and through direct action on other proteins such as mitochondrial complexes involved in cellular respiration. Thus, the aim of this study was to determine the actions of a panel of extracts, isolated from high-CBD varieties of Cannabis sativa, on the activity of the mitochondrial electron transport chain complex IV, cytochrome c oxidase (CCO), in order to select those with a safer profile. After demonstrating that Cannabis sativa strains could be identified by cannabinoids content, concentration–response curves were performed with a collection of extracts from strains with high-CBD and low-THC content using bovine CCO. The CCO rate was clearly modified by specific extracts of Cannabis sativa plants compared to others. Half maximal inhibitory concentrations (IC50) of extracts and the inhibitory effects evoked at 1 × 10−4 g/mL displayed a significant correlation with the THC. Therefore, the screening of extracts based on CCO activity provides a powerful and rapid methodology to identify those plants with higher mitochondrial toxicity or even mito-protective actions.
Phenylsulfonimide PPARα Antagonists Enhance Nrf2 Activation and Promote Oxidative Stress-Induced Apoptosis/Pyroptosis in MCF7 Breast Cancer Cells
Authors: Gallorini Marialucia , Di Valerio Valentina , Bruno Isabella , Carradori Simone , Amoroso Rosa , Cataldi Amelia , Ammazzalorso Alessandra
Published: January 2023

The NF-E2-related factor 2 transcription factor (Nrf2) orchestrates the basal and stress-inducible activation of a vast array of antioxidant genes. A high amount of reactive oxygen species (ROS) promotes carcinogenesis in cells with defective redox-sensitive signaling factors such as Nrf2. In breast cancer (BC), emerging evidence indicates that increased Nrf2 activity enhances cell metastatic potential. An interconnection between peroxisome proliferator-activated receptors (PPARs) and Nrf2 pathways in cancer has been shown. In this light, newly synthesized PPARα antagonists, namely IB42, IB44, and IB66, were tested in the BC cell line MCF7 in parallel with GW6471 as the reference compound. Our results show that the most promising compound of this phenylsulfonimide series (IB66) is able to decrease MCF7 proliferation by blocking cells at the G2/M checkpoint. The underlying mechanism has been investigated, disclosing a caspase 3/Akt-dependent apoptotic/pyroptotic pathway induced by the increased generation of oxidative stress. Moreover, the involvement of Nrf2 and COX2 in IB66-treated MCF7 cell response has been highlighted. The reported data lay the groundwork for the development of alternative targeted therapy involving the Nrf2/PPARα molecular axis, able to overcome BC cell chemoresistance and cause better clinical outcomes, promoting other forms of programmed cell death, such as pyroptosis.
Domain Truncation in Hispidin Synthase Orthologs from Non-Bioluminescent Fungi Does Not Lead to Hispidin Biosynthesis
Authors: Palkina Kseniia A. , Balakireva Anastasia V. , Belozerova Olga A. , Chepurnykh Tatiana V. , Markina Nadezhda M. , Kovalchuk Sergey I. , Tsarkova Aleksandra S. , Mishin Alexander S. , Yampolsky Ilia V. , Sarkisyan Karen S.
Published: January 2023

Hispidin is a polyketide found in plants and fungi. In bioluminescent fungi, hispidin serves as a precursor of luciferin and is produced by hispidin synthases. Previous studies revealed that hispidin synthases differ in orthologous polyketide synthases from non-bioluminescent fungi by the absence of two domains with predicted ketoreductase and dehydratase activities. Here, we investigated the hypothesis that the loss of these domains in evolution led to the production of hispidin and the emergence of bioluminescence. We cloned three orthologous polyketide synthases from non-bioluminescent fungi, as well as their truncated variants, and assessed their ability to produce hispidin in a bioluminescence assay in yeast. Interestingly, expression of the full-length enzyme hsPKS resulted in dim luminescence, indicating that small amounts of hispidin are likely being produced as side products of the main reaction. Deletion of the ketoreductase and dehydratase domains resulted in no luminescence. Thus, domain truncation by itself does not appear to be a sufficient step for the emergence of efficient hispidin synthases from orthologous polyketide synthases. At the same time, the production of small amounts of hispidin or related compounds by full-length enzymes suggests that ancestral fungal species were well-positioned for the evolution of bioluminescence.
Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk
Authors: Martinelli Marianna , Giubbi Chiara , Saderi Laura , Musumeci Rosario , Perdoni Federica , Leone Biagio Eugenio , Fruscio Robert , Landoni Fabio , Piana Andrea , Sotgiu Giovanni , Cocuzza Clementina Elvezia
Published: January 2023

HPV testing in cervical cancer screening programs offers the possibility of introducing molecular standardized biomarkers for the triage of HPV-positive women. This study aimed to evaluate the role of HPV genotyping and viral load as possible diagnostic biomarkers of high-grade cervical lesions (CIN2+) by performing a preliminary evaluation of a new HPV test. Cervical specimens were obtained from 200 women referred for a colposcopy. Samples were tested using both Anyplex™ II HR-HPV as well as OncoPredict HPV® Screening (SCR) and quantitative typing (QT). Using a cycle threshold cutoff (Ct) of 36.8 for the SCR assay and 1.27 log10 (viral copies/104 cells) for the QT assay, relative clinical sensitivity for CIN2+ and relative clinical specificity for CIN2− as compared to Anyplex™ II HR-HPV were, respectively, 0.92 and 1.00 for SCR and 1.35 and 1.24 for QT. The distribution of high-risk HPV (HR-HPV) genotypes (p = 0.009) as well as the viral copy numbers (CIN2−: 3.7 log10 (viral copies/104 human cells); CIN2+: 4.3 log10 (viral copies/104 human cells); p = 0.047) were found to differ in women with high- and low-grade cervical lesions, suggesting a possible role of HPV genotyping and normalized viral load as potential biomarkers to identify women at increased risk of cervical lesions.
Involvement of Vasopressin in Tissue Hypoperfusion during Cardiogenic Shock Complicating Acute Myocardial Infarction in Rats
Authors: Gaudard Philippe , David Hélène , Bideaux Patrice , Sicard Pierre , Cristol Jean-Paul , Guillon Gilles , Richard Sylvain , Colson Pascal , Virsolvy Anne
Published: January 2023

Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D1) and after hemodynamic parameters determination. Vascular responses to vasopressin were evaluated, ex vivo, on aorta. AHF was defined by a left ventricular ejection fraction below 40%. CS was defined by AHF plus tissue hypoperfusion evidenced by elevated serum lactate level or low mesenteric oxygen saturation (SmO2) at D1. Mortality rates were 40% in AMI, 0% in AMI-SR and 33% in AMI-TLP. Immediately after surgery, a sharp decrease in SmO2 was observed in all groups. At D1, SmO2 recovered in Sham and in SR-treated animals while it remained low in AMI and further decreased in TLP-treated groups. The incidence of CS among AHF animals was 72% in AMI or AMI-TLP while it was reduced to 25% in AMI-SR. Plasma copeptin level was increased by AMI. Maximal contractile response to vasopressin was decreased in AMI (32%) as in TLP- and SR- treated groups regardless of ligation. Increased vasopressin secretion occurring in the early phase of AMI may be responsible of mesenteric hypoperfusion resulting in tissue hypoxia. Treatment with a vasopressin antagonist enhanced mesenteric perfusion and improve survival. This could be an interesting therapeutic strategy to prevent progression to cardiogenic shock.
siRNA-Mediated MELK Knockdown Induces Accelerated Wound Healing with Increased Collagen Deposition
Authors: Szymanski Lukasz , Lewicki Sławomir , Markiewicz Tomasz , Cierniak Szczepan , Tassan Jean-Pierre , Kubiak Jacek Z.
Published: January 2023

Skin wounds remain a significant problem for the healthcare system, affecting the clinical outcome, patients’ quality of life, and financial costs. Reduced wound healing times would improve clinical, economic, and social aspects for both patients and the healthcare system. Skin wound healing has been studied for years, but effective therapy that leads to accelerated wound healing remains to be discovered. This study aimed to evaluate the potential of MELK silencing to accelerate wound healing. A vectorless, transient knockdown of the MELK gene using siRNA was performed in a murine skin wound model. The wound size, total collagen, type 3 collagen, vessel size, vessel number, cell proliferation, cell apoptosis, number of mast cells, and immune infiltration by CD45, CD11b, CD45, and CD8a cells were evaluated. We observed that treatment with MELK siRNA leads to significantly faster wound closing associated with increased collagen deposition.