bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual Aircraft Noise Exposure Assessment for a Case-Crossover Study in Switzerland
Authors: Saucy Apolline , Schäffer Beat , Tangermann Louise , Vienneau Danielle , Wunderli Jean-Marc , Röösli Martin
Published: April 2020

Accurate exposure assessment is essential in environmental epidemiological studies. This is especially true for aircraft noise, which is characterized by a high spatial and temporal variation. We propose a method to assess individual aircraft noise exposure for a case-crossover study investigating the acute effects of aircraft noise on cardiovascular deaths. We identified all cases of cardiovascular death (24,886) occurring near Zürich airport, Switzerland, over fifteen years from the Swiss National Cohort. Outdoor noise exposure at the home address was calculated for the night preceding death and control nights using flight operations information from Zürich airport and noise footprints calculated for major aircraft types and air routes. We estimated three different noise metrics: mean sound pressure level (LAeq), maximum sound pressure level (LAmax), and number above threshold 55 dB (NAT55) for different nighttime windows. Average nighttime aircraft noise levels were 45.2 dB, 64.6 dB, and 18.5 for LAeq, LAmax, and NAT55 respectively. In this paper, we present a method to estimate individual aircraft noise exposure with high spatio-temporal resolution and a flexible choice of exposure events and metrics. This exposure assessment will be used in a case-crossover study investigating the acute effects of noise on health.
Effects of Lifting Method, Safety Shoe Type, and Lifting Frequency on Maximum Acceptable Weight of Lift, Physiological Responses, and Safety Shoes Discomfort Rating
Authors: Alferdaws Fares F. , Ramadan Mohamed Z.
Published: April 2020

This study aimed to investigate the physical effects of precision lifting tasks on the maximal acceptable weight of a lift (i.e., psychophysiological lifting capacity where the workers adjust the lifting weight in order to work without any fatigue or strain at the end of the work while wearing common safety shoe types). Additionally, the physical difference between the precise and non-precise lifting conditions associated with wearing safety shoes were assessed by respiration responses and shoe discomfort ratings. To achieve the objective of the study, ten healthy male workers were selected by age (between 25 to 35 years old). Their anthropometric characteristics, including knuckle height, knee height, and body mass index (BMI), were measured. A three-way repeated measures design with three independent variables was used; the variables included—the (1) lifting method (precise and non-precise), (2) lifting frequency (1 and 4 lifts per min), and (3) safety shoe type (light-duty, medium-duty, and heavy-duty). The physiological response variables and one of the subjective factors of this study were—(1) respiration responses, and (2) shoe discomfort rating, respectively. The data were analyzed using the Mauchly’s test of sphericity, Shapiro–Wilk normality test, and analysis of variance (ANOVA). The results showed that the use of heavy-duty safety shoes typically increased the shoe discomfort rating under precise lifting methods. Additionally, the lifting frequency was determined to be one of the main factors affecting respiratory responses and shoe discomfort rating. This study also found that respiration responses rose on four lifts per min as compared to 1 lift per min, regardless of the lifting method type. This study indicated that the replacement of some types of ordinary safety shoes used in some workplaces with those selected appropriately might significantly reduce the rating effort required to lift objects or tools. However, the benefits should be carefully evaluated before replacing the safety shoes.
Hair Cortisol Concentrations as a Biomarker to Predict a Clinical Pregnancy Outcome after an IVF Cycle: A Pilot Feasibility Study
Authors: C. Santa-Cruz Diana , Caparros-Gonzalez Rafael A. , Romero-Gonzalez Borja , Peralta-Ramirez Maria Isabel , Gonzalez-Perez Raquel , García-Velasco Juan Antonio
Published: April 2020

Our objective was to examine the feasibility of hair cortisol concentrations (HCC) as a biomarker to predict clinical pregnancy outcomes and investigate its potential associations with perceived anxiety, resilience, and depressive symptoms. A total of 43 participants were assessed using HCC, the state trait anxiety inventory (STAI), resilience scale (RS), and the depression subscale of the symptom checklist 90-R (SCL-90-R). Participants were approached at their second consultation with the reproductive endocrinologist (T1), before scheduling their IVF cycle, and then 12 weeks after (T2), at their post-transfer visit with the study coordinators, before the human chorionic gonadotropin (HCG) pregnancy test. The logistic regression model revealed that HCC at T2 predicted 46% of a positive pregnancy test [R2 = 0.46, (ß = 0.11, p < 0.05)]. Pregnant women had higher levels of resilience at T2 (M = 149.29; SD = 17.56) when compared with non-pregnant women at T2 (M = 119.96; SD = 21.71). Significant differences were found between both groups in depression at T2 (t = 3.13, p = 0.01) and resilience at T2 (t = −4.89, p = 0.01). HCC might be a promising biomarker to calculate the probability of pregnancy in women using assisted reproductive technologies (ART).
Child Salivary SIgA and Its Relationship to Enteric Infections and EED Biomarkers in Maputo, Mozambique
Authors: Goddard Frederick G. B. , Knee Jacqueline , Sumner Trent , Nalá Rassul , Clasen Thomas , Brown Joe
Published: April 2020

Characterizing child immunological responses to enteric infections with antibody detection in serum can be challenging in resource-constrained field settings, because sample collection requires trained individuals and its invasive procedure may lead to low response rates, especially among children. Saliva may present a promising non-invasive alternative. The objectives of this research were to compare salivary antibody levels in children to enteric infections and biomarkers of environmental enteric dysfunction (EED). We collected saliva samples from children aged one to six years enrolled in a sanitation trial in Maputo, Mozambique, and characterized salivary secretory immunoglobulin A (SIgA) concentrations with enzyme-linked immunosorbent assays. We used multilevel linear models to analyze cross-sectional associations between salivary SIgA and the number of concurrent enteric pathogen infections, as well as EED biomarkers in matched stool samples. Median salivary SIgA concentrations in this study population were 54 μg/mL (inter-quartile range (IQR): 34, 85 μg/mL), and SIgA levels were similar between children of different ages. SIgA was lower in children experiencing a higher number of concurrent infections −0.04 log μg/mL (95% confidence interval (CI): −0.08 to −0.005 log μg/mL), but was not associated with any of the included EED biomarkers. Contrary to evidence from high-income countries that suggests salivary SIgA increases rapidly with age in young children, the high prevalence of enteric infections may have led to a suppression of immunological development in this study sample and could in part explain the similar SIgA levels between children of different ages.
Experiences of the Initial Phase Implementation of the STAMINA-Model in Perioperative Context Addressing Environmental Issues Systematically—A Qualitative Study
Authors: Arakelian Erebouni , Hellman Therese , Svartengren Magnus
Published: April 2020

(1) Background: Challenges in perioperative settings put demands on staff working with systematic work environment management. A support model, STAMINA (Structured and Time-effective Approach through Methods for an Inclusive and Active working life), was implemented in a hospital in Sweden, to help staff address environmental issues systematically. The aim was to describe the experiences of the initial phase of implementation of the adapted STAMINA model in perioperative context. (2) Methods: Qualitative individual interviews were held with 14 managers and employees (three men and 11 women). Data were analysed by systematic text condensation. (3) Results: Five themes were identified: Limited knowledge of the model and the implementation process; scepticism, lack of confidence in the model and a passive attitude; the model offered increased participation; the culture in the organization—to understand one’s role as employees and managers; and endurance and feedback are key factors for success in the implementation process. (4) Conclusions: Scepticism turned to positive attitude by recognising that the STAMINA model offered increased participation. In order to have successful implementation, the organisational culture must be taken into consideration by giving the employees increased responsibilities and timely feedbacks. Role description, goal definition, feedback, and sticking to one model are key factors for success.
Determinants of Active and Healthy Ageing in Sub-Saharan Africa: Evidence from Cameroon
Authors: Naah Fomba Louisette , Njong Aloysius Mom , Kimengsi Jude Ndzifon
Published: April 2020

This paper examines the determinants and policy implications of active and healthy ageing in Sub-Saharan Africa, taking the case of Bamenda, in Cameroon. Specifically, the study sought to identify and explore the determinants of active and healthy ageing using a mixed-methods approach involving qualitative and quantitative data collection and analysis. Focus group discussions were conducted complemented by a survey (random and snowball sampling) using a structured questionnaire. Narratives and thematic analysis were used to analyze the data generated from the focus group discussion and Tobit regression was employed to analyze the multiple determinants of active ageing by dimensions and on a global scale in Cameroon. Results identified three key dimensions of active and healthy ageing: employment/livelihood options (EL), community support and health (CH) and housing and living in Bamenda (HL). The regression results reveal gender bias in active ageing, a non-effect of education and health on active ageing, and a positive effect of income on active and healthy ageing. This study contributes, among others, to the competence–environmental press theory on active ageing with regards to unbundling context specific determinants of active and healthy ageing. It equally derives policy considerations with regards to gender mainstreaming and the identification of age friendly income earning options to enhance the active and healthy ageing process.
A Qualitative Evaluation of Adverse Drug Reaction Reporting System in Pakistan: Findings from the Nurses’ Perspective
Authors: Hussain Rabia , Hassali Mohamed Azmi , ur Rehman Anees , Muneswarao Jaya , Atif Muhammad , Babar Zaheer-Ud-Din
Published: April 2020

The contribution of all key healthcare professionals is vital to promote an efficient adverse drug reaction (ADR) reporting system. In this context, nurses are important as they are in a better position to observe a patient’s response regarding the drug therapy and to report an ADR. The aim of the study was to explore the perspectives of nurses about ADR reporting system in Lahore, Pakistan. A total of 21 nurses were interviewed. The thematic content analysis of the qualitative interviews yielded six major themes and eight subthemes. Major themes included: (1) Knowledge about the concept of the medication safety & the ADR; (2) Knowledge regarding pharmacovigilance activities; (3) Willingness to report; (4) Practices related to the ADR reporting; (5) Barriers to the ADR reporting; (6) Facilitators to the ADR reporting. The majority of the nurses were aware of medicine safety and ADRs, but in many cases, they were unable to report these ADRs. The study pointed out considerable concerns regarding the knowledge and practices of nurses about pharmacovigilance activities in their workplace, mainly due to increased workload, due to the absence of a reporting system and legal liability. The main challenges turned out to be the lack of knowledge and training, as well as the implementation of guidelines. Based on the findings, it is suggested that outcome of this study can serve as a guide to design policies that support ADR reporting by nurses in Pakistan.
Effect of Particulate Matter Exposure on Respiratory Health of e-Waste Workers at Agbogbloshie, Accra, Ghana
Authors: Amoabeng Nti Afua Asabea , Arko-Mensah John , Botwe Paul K. , Dwomoh Duah , Kwarteng Lawrencia , Takyi Sylvia Akpene , Acquah Augustine Appah , Tettey Prudence , Basu Niladri , Batterman Stuart , Robins Thomas G. , Fobil Julius N.
Published: April 2020

Background: Direct and continuous exposure to particulate matter (PM), especially in occupational settings is known to impact negatively on respiratory health and lung function. Objective: To determine the association between concentrations of PM (2.5, 2.5–10 and 10 µm) in breathing zone and lung function of informal e-waste workers at Agbogbloshie. Methods: To evaluate lung function responses to PM (2.5, 2.5–10 and 10 µm), we conducted a longitudinal cohort study with three repeated measures among 207 participants comprising 142 healthy e-waste workers from Agbogbloshie scrapyard and 65 control participants from Madina-Zongo in Accra, Ghana from 2017–2018. Lung function parameters (FVC, FEV1, FEV1/FVC, PEF, and FEF 25-75) and PM (2.5, 2.5–10 and 10 µm) concentrations were measured, corresponding to prevailing seasonal variations. Socio-demographic data, respiratory exposures and lifestyle habits were determined using questionnaires. Random effects models were then used to examine the effects of PM (2.5, 2.5–10 and 10 µm) on lung function. Results: The median concentrations of PM (2.5, 2.5–10 and 10 µm) were all consistently above the WHO ambient air standards across the study waves. Small effect estimates per IQR of PM (2.5, 2.5–10 and 10 µm) on lung function parameters were observed even after adjustment for potential confounders. However, a 10 µg increase in PM (2.5, 2.5–10 and 10 µm) was associated with decreases in PEF and FEF 25–75 by 13.3% % [β = −3.133; 95% CI: −0.243, −0.022) and 26.6% [β = −0.266; 95% CI: −0.437, 0.094]. E-waste burning and a history of asthma significantly predicted a decrease in PEF by 14.2% [β = −0.142; 95% CI: −0.278, −0.008) and FEV1 by 35.8% [β = −0.358; 95% CI: −0.590, 0.125] among e-waste burners. Conclusions: Direct exposure of e-waste workers to PM predisposes to decline in lung function and risk for small airway diseases such as asthma and COPD.
Five Challenges When Managing Mass Casualty or Disaster Situations: A Review Study
Authors: Hugelius Karin , Becker Julia , Adolfsson Annsofie
Published: April 2020

Background: Managing mass casualty or disaster incidents is challenging to any person or organisation. Therefore, this paper identifies and describes common challenges to managing such situations, using case and lessons learned reports. It focuses on sudden onset, man-made or technologically caused mass casualty or disaster situations. Methods: A management review was conducted based on a structured search in the PubMed and Web of Science databases. Results: The review included 20 case—and lessons learned reports covering natural disasters, man-made events, and accidents across Europe, the United States of Amerika (USA), Asia and the Middle East. Five common challenges were identified: (1) to identify the situation and deal with uncertainty, (2) to balance the mismatch between the contingency plan and the reality, (3) to establish a functional crisis organization, (4) to adapt the medical response to the actual and overall situation and (5) to ensure a resilient response. Conclusions: The challenges when managing mass casualty or disaster events involved were mainly related to the ability to manage uncertainty and surprising situations, using structured processes to respond. The ability to change mind set, organization and procedures, both from an organizational- and individual perspective, was essential. Non-medical factors and internal factors influenced the medical management. In order to respond in an effective, timely and resilient way, all these factors should be taken into consideration.
An Inventory of European Birth Cohorts
Authors: Pansieri Claudia , Pandolfini Chiara , Clavenna Antonio , Choonara Imti , Bonati Maurizio
Published: April 2020

Many birth cohorts have been carried out. We performed a review of European birth cohorts to see the countries involved, provide a panorama of the current research topics and design, and, more generally, provide input for those creating collaborations and laying out guidelines aimed at unifying cohort methodologies to enable data merging and maximize knowledge acquisition. We searched PubMed and Embase for articles referring to longitudinal, prospective European birth cohorts and searched online cohort inventories. We found references to 111 birth cohorts, 45 of which began enrolment at birth. These cohorts began between 1921 and 2015 and represented 19 countries, with varying sample sizes (236 to 21,000 children). As of 5 January 2020, were still recruiting. The main areas addressed were allergic diseases (14 cohorts) and environmental exposure (f12 cohorts) and most cohorts were publicly funded. Given the large costs of running cohorts and the importance of long follow-up periods in identifying the risk factors for disorders thought to have a perinatal/early life etiology, current cohorts must be designed to answer research questions considering several aspects, from genetic ones to psychological, social, and environmental ones. Furthermore, universally recognized methodological aspects are needed to permit the comparison and merging of cohort data.
Tetragonia tetragonioides Protected against Memory Dysfunction by Elevating Hippocampal Amyloid-β Deposition through Potentiating Insulin Signaling and Altering Gut Microbiome Composition
Authors: Kim Da Sol , Ko Byoung-Seob , Ryuk Jin Ah , Park Sunmin
Published: April 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Herbal medicine may provide efficacious treatments for its prevention and/or cure. This study investigated whether a 70% ethanol extract of Tetragonia tetragonioides Kuntze (TTK; New Zealand spinach) improved the memory deficit by reducing hippocampal amyloid-β deposition and modulating the gut microbiota in rats with amyloid-β(25–35) infused into the hippocampus (AD rats) in an AD animal model. The AD rats had cellulose (AD-CON) or TTK (300 mg/kg bw; AD-TTK) in their high-fat diets for seven weeks. Rats with amyloid-β(35–25) infused into the hippocampus fed an AD-Con diet did not have memory loss (Normal-Con). AD-TTK protected against amyloid-β deposition compared to AD-Con, but it was higher than Normal-Con. AD-TTK protected against short-term and special memory loss measured by passive avoidance, Y maze, and water maze, compared to AD-Con. Compared to the Normal-Con, AD-Con attenuated hippocampal pCREB → pAkt → pGSK-3β, which was prevented in the AD-TTK group. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) mRNA expression decreased in the AD-CON group, and their expression was prevented in the AD-TTK group. Hippocampal TNF-α and IL-1β mRNA expressions were higher in the AD-Con group than in the Normal-Con, and AD-TTK groups protected against the increase in their expression. The AD-CON group showed an increase in insulin resistance compared to the Normal-Con group and the AD-TTK group showed improvement. AD-Con separated the gut microbiome community compared to the Normal-Con group and AD-TTK overlapped with the normal-Con. The AD-Con group had more Clostridiales, Erysipelotrichales, and Desulfovibrionales than the AD-TKK and Normal-Con group but fewer Lactobacilales and Bacteroidales. In conclusion, the 70% ethanol extract of TTK enhanced the memory function and potentiated hippocampal insulin signaling, reduced insulin resistance, and improved gut microbiota in amyloid-β-infused rats.
PDE2A Is Indispensable for Mouse Liver Development and Hematopoiesis
Authors: Barbagallo Federica , Rotilio Valentina , Assenza Maria Rita , Aguanno Salvatore , Orsini Tiziana , Putti Sabrina , Isidori Andrea M. , Lenzi Andrea , Naro Fabio , De Angelis Luciana , Pellegrini Manuela
Published: April 2020

Phosphodiesterase 2A (PDE2A) is a cAMP-cGMP hydrolyzing enzyme essential for mouse development and the PDE2A knockout model (PDE2A−/−) is embryonic lethal. Notably, livers of PDE2A−/− embryos at embryonic day 14.5 (E14.5) have extremely reduced size. Morphological, cellular and molecular analyses revealed loss of integrity in the PDE2A−/− liver niche that compromises the hematopoietic function and maturation. Hematopoietic cells isolated from PDE2A−/− livers are instead able to differentiate in in vitro assays, suggesting the absence of blood cell-autonomous defects. Apoptosis was revealed in hepatoblasts and at the endothelial and stromal compartments in livers of PDE2A−/− embryos. The increase of the intracellular cAMP level and of the inducible cAMP early repressor (ICER) in liver of PDE2A−/− embryos might explain the impairment of liver development by downregulating the expression of the anti-apoptotic gene Bcl2. In summary, we propose PDE2A as an essential gene for integrity maintenance of liver niche and the accomplishment of hematopoiesis.
Effects of Cholesterol in Stress-Related Neuronal Death—A Statistical Analysis Perspective
Authors: Dayeh Maher A. , Livadiotis George , Aminian Farzan , Cheng Kwan H. , Roberts James L. , Viswasam Nikita , Elaydi Saber
Published: April 2020

The association between plasma cholesterol levels and the development of dementia continues to be an important topic of discussion in the scientific community, while the results in the literature vary significantly. We study the effect of reducing oxidized neuronal cholesterol on the lipid raft structure of plasma membrane. The levels of plasma membrane cholesterol were reduced by treating the intact cells with methyl-ß-cyclodextrin (MßCD). The relationship between the cell viability with varying levels of MßCD was then examined. The viability curves are well described by a modified form of the empirical Gompertz law of mortality. A detailed statistical analysis is performed on the fitting results, showing that increasing MßCD concentration has a minor, rather than significant, effect on the cellular viability. In particular, the dependence of viability on MßCD concentration was found to be characterized by a ~25% increase per 1 μM of MßCD concentration.
Elimination of Viroids from Tobacco Pollen Involves a Decrease in Propagation Rate and an Increase of the Degradation Processes
Authors: Matoušek Jaroslav , Steinbachová Lenka , Drábková Lenka Záveská , Kocábek Tomáš , Potěšil David , Mishra Ajay Kumar , Honys David , Steger Gerhard
Published: April 2020

Some viroids—single-stranded, non-coding, circular RNA parasites of plants—are not transmissible through pollen to seeds and to next generation. We analyzed the cause for the elimination of apple fruit crinkle viroid (AFCVd) and citrus bark cracking viroid (CBCVd) from male gametophyte cells of Nicotiana tabacum by RNA deep sequencing and molecular methods using infected and transformed tobacco pollen tissues at different developmental stages. AFCVd was not transferable from pollen to seeds in reciprocal pollinations, due to a complete viroid eradication during the last steps of pollen development and fertilization. In pollen, the viroid replication pathway proceeds with detectable replication intermediates, but is dramatically depressed in comparison to leaves. Specific and unspecific viroid degradation with some preference for (−) chains occurred in pollen, as detected by analysis of viroid-derived small RNAs, by quantification of viroid levels and by detection of viroid degradation products forming “comets” on Northern blots. The decrease of viroid levels during pollen development correlated with mRNA accumulation of several RNA-degrading factors, such as AGO5 nuclease, DICER-like and TUDOR S-like nuclease. In addition, the functional status of pollen, as a tissue with high ribosome content, could play a role during suppression of AFCVd replication involving transcription factors IIIA and ribosomal protein L5.
Evaluation of Droplet Digital Polymerase Chain Reaction (ddPCR) for the Absolute Quantification of Aspergillus species in the Human Airway
Authors: Poh Tuang Yeow , Ali Nur A’tikah Binte Mohamed , Chan Louisa L.Y. , Tiew Pei Yee , Chotirmall Sanjay H.
Published: April 2020

Background: Prior studies illustrate the presence and clinical importance of detecting Aspergillus species in the airways of patients with chronic respiratory disease. Despite this, a low fungal biomass and the presence of PCR inhibitors limits the usefulness of quantitative PCR (qPCR) for accurate absolute quantification of Aspergillus in specimens from the human airway. Droplet digital PCR (ddPCR) however, presents an alternative methodology allowing higher sensitivity and accuracy of such quantification but remains to be evaluated in head-to-head fashion using specimens from the human airway. Here, we implement a standard duplex TaqMan PCR protocol, and assess if ddPCR is superior in quantifying airway Aspergillus when compared to standard qPCR. Methods: The molecular approaches of qPCR and ddPCR were applied to DNA fungal extracts in n = 20 sputum specimens obtained from non-diseased (n = 4), chronic obstructive pulmonary disease (COPD; n = 8) and non-cystic fibrosis bronchiectasis (n = 8) patients where Aspergillus status was known. DNA was extracted and qPCR and ddPCR performed on all specimens with appropriate controls and head-to-head comparisons performed. Results: Standard qPCR and ddPCR were both able to detect, even at low abundance, Aspergillus species (Aspergillus fumigatus - A. fumigatus and Aspergillus terreus - A. terreus) from specimens known to contain the respective fungi. Importantly, however, ddPCR was superior for the detection of A. terreus particularly when present at very low abundance and demonstrates greater resistance to PCR inhibition compared to qPCR. Conclusion: ddPCR has greater sensitivity for A. terreus detection from respiratory specimens, and is more resistant to PCR inhibition, important attributes considering the importance of A. terreus species in chronic respiratory disease states such as bronchiectasis.
Airway Microbiota as a Modulator of Lung Cancer
Authors: Goto Taichiro
Published: April 2020

Recent research on cancer-associated microbial communities has elucidated the interplay between bacteria, immune cells, and tumor cells; the bacterial pathways involved in the induction of carcinogenesis; and their clinical significance. Although accumulating evidence shows that a dysbiotic condition is associated with lung carcinogenesis, the underlying mechanisms remain unclear. Microorganisms possibly trigger tumor initiation and progression, presumably via the production of bacterial toxins and other pro-inflammatory factors. The purpose of this review is to discuss the basic role of the airway microbiome in carcinogenesis and the underlying molecular mechanisms, with the aim of developing anticancer strategies involving the airway microbiota. In addition, the mechanisms via which the microbiome acts as a modulator of immunotherapies in lung cancer are summarized.
Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?
Authors: Ziganshina Marina M. , Yarotskaya Ekaterina L. , Bovin Nicolai V. , Pavlovich Stanislav V. , Sukhikh Gennady T.
Published: April 2020

Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.
Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain
Authors: Mucignat-Caretta Carla , Caretta Antonio
Published: April 2020

Protein kinase A (PKA) are tetramers of two catalytic and two regulatory subunits, docked at precise intracellular sites to provide localized phosphorylating activity, triggered by cAMP binding to regulatory subunits and subsequent dissociation of catalytic subunits. It is unclear whether in the brain PKA dissociated subunits may also be found. PKA catalytic subunit was examined in various mouse brain areas using immunofluorescence, equilibrium binding and western blot, to reveal its location in comparison to regulatory subunits type RI and RII. In the cerebral cortex, catalytic subunits colocalized with clusters of RI, yet not all RI clusters were bound to catalytic subunits. In stria terminalis, catalytic subunits were in proximity to RI but separated from them. Catalytic subunits clusters were also present in the corpus striatum, where RII clusters were detected, whereas RI clusters were absent. Upon cAMP addition, the distribution of regulatory subunits did not change, while catalytic subunits were completely released from regulatory subunits. Unpredictably, catalytic subunits were not solubilized; instead, they re-targeted to other binding sites within the tissue, suggesting local macromolecular reorganization. Hence, the interactions between catalytic and regulatory subunits of protein kinase A consistently vary in different brain areas, supporting the idea of multiple interaction patterns.
A Comparison of Immune Responses Exerted Following Syngeneic, Allogeneic, and Xenogeneic Transplantation of Mesenchymal Stem Cells into the Mouse Brain
Authors: Hwang Jung Won , Lee Na Kyung , Yang Je Hoon , Son Hyo Jin , Bang Sa Ik , Chang Jong Wook , Na Duk L.
Published: April 2020

Due to their multifactorial aspects, mesenchymal stem cells (MSCs) have been widely established as an attractive and potential candidate for the treatment of a multitude of diseases. A substantial number of studies advocate that MSCs are poorly immunogenic. In several studies, however, immune responses were observed following injections of xenogeneic donor MSCs. In this study, the aim was to examine differences in immune responses exerted based on transplantations of xenogeneic, syngeneic, and allogeneic MSCs in the wild-type mouse brain. Xenogeneic, allogeneic, and syngeneic MSCs were intracerebrally injected into C57BL/6 mice. Mice were sacrificed one week following transplantation. Based on immunohistochemical (IHC) analysis, leukocytes and neutrophils were expressed at the injection sites in the following order (highest to lowest) xenogeneic, allogeneic, and syngeneic. In contrast, microglia and macrophages were expressed in the following order (highest to lowest): syngeneic, allogeneic, and xenogeneic. Residual human MSCs in the mouse brain were barely detected after seven days. Although the discrepancy between leukocytes versus macrophages/microglia infiltration should be resolved, our results overall argue against the previous notions that MSCs are poorly immunogenic and that modulation of immune responses is a prerequisite for preclinical and clinical studies in MSC therapy of central nervous system diseases.
Immune Checkpoint Inhibitor-Related Myositis: From Biology to Bedside
Authors: Solimando Antonio G. , Crudele Lucilla , Leone Patrizia , Argentiero Antonella , Guarascio Matteo , Silvestris Nicola , Vacca Angelo , Racanelli Vito
Published: April 2020

Immune checkpoint inhibitor (ICI)-related inflammatory diseases, including polymyositis (PM) and dermatomyositis (DM), in patients suffering from neoplastic disorders represent a medical challenge. The treatment of these conditions has taken on new urgency due to the successful and broad development of cancer-directed immunological-based therapeutic strategies. While primary and secondary PM/DM phenotypes have been pathophysiologically characterized, a rational, stepwise approach to the treatment of patients with ICI-related disease is lacking. In the absence of high-quality evidence to guide clinical judgment, the available data must be critically assessed. In this literature review, we examine partially neglected immunological and clinical findings to obtain insights into the biological profiles of ICI-related PM/DM and potential treatment options. We show that differential diagnosis is essential to stratifying patients according to prognosis and therapeutic impact. Finally, we provide a comprehensive assessment of druggable targets and suggest a stepwise patient-oriented approach for the treatment of ICI-related PM/DM.
Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip
Authors: Goto Kaku , Roca Suarez Armando Andres , Wrensch Florian , Baumert Thomas F. , Lupberger Joachim
Published: April 2020

Chronic infection with hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC). Novel treatments with direct-acting antivirals achieve high rates of sustained virologic response; however, the HCC risk remains elevated in cured patients, especially those with advanced liver disease. Long-term HCV infection causes a persistent and accumulating damage of the liver due to a combination of direct and indirect pro-oncogenic mechanisms. This review describes the processes involved in virus-induced disease progression by viral proteins, derailed signaling, immunity, and persistent epigenetic deregulation, which may be instrumental to develop urgently needed prognostic biomarkers and as targets for novel chemopreventive therapies.
In Vitro Salivary Protein Adsorption Profile on Titanium and Ceramic Surfaces and the Corresponding Putative Immunological Implications
Authors: Wei Chen-Xuan , Burrow Michael Francis , Botelho Michael George , Lam Henry , Leung Wai Keung
Published: April 2020

Immune responses triggered by implant abutment surfaces contributed by surface-adsorbed proteins are critical in clinical implant integration. How material surface-adsorbed proteins relate to host immune responses remain unclear. This study aimed to profile and address the immunological roles of surface-adsorbed salivary proteins on conventional implant abutment materials. Standardized polished bocks (5 × 5 × 1 mm3) were prepared from titanium and feldspathic ceramic. Salivary acquired pellicle formed in vitro was examined by liquid chromatography-tandem mass spectrometry and gene ontology (GO) analysis to identify and characterize the adsorbed proteins. Out of 759 proteins identified from pooled saliva samples, 396 were found to be attached to the two materials tested—369 on titanium and 298 on ceramic, with 281 common to both. GO annotation of immune processes was undertaken to form a protein–protein interaction network, and 14 hub proteins (≥6 interaction partners) (coding genes: B2M, C3, CLU, DEFA1, HSP90AA1, HSP90AB1, LTF, PIGR, PSMA2, RAC1, RAP1A, S100A8, S100A9, and SLP1) were identified as the key proteins connecting multiple (6–9) immune processes. The results offered putative immunological prospects of implant abutment material surface-adsorbed salivary proteins, which could potentially underpin the dynamic nature of implant–mucosal/implant–microbial interactions.
Genome-Wide Identification and Characterization of UTR-Introns of Citrus sinensis
Authors: Shi Xiaobao , Wu Junwei , Mensah Raphael Anue , Tian Na , Liu Jiapeng , Liu Fan , Chen Jialan , Che Jingru , Guo Ye , Wu Binghua , Zhong Guangyan , Cheng Chunzhen
Published: April 2020

Introns exist not only in coding sequences (CDSs) but also in untranslated regions (UTRs) of a gene. Recent studies in animals and model plants such as Arabidopsis have revealed that the UTR-introns (UIs) are widely presented in most genomes and involved in regulation of gene expression or RNA stability. In the present study, we identified introns at both 5′UTRs (5UIs) and 3′UTRs (3UIs) of sweet orange genes, investigated their size and nucleotide distribution characteristics, and explored the distribution of cis-elements in the UI sequences. Functional category of genes with predicted UIs were further analyzed using GO, KEGG, and PageMan enrichment. In addition, the organ-dependent splicing and abundance of selected UI-containing genes in root, leaf, and stem were experimentally determined. Totally, we identified 825 UI- and 570 3UI-containing transcripts, corresponding to 617 and 469 genes, respectively. Among them, 74 genes contain both 5UI and 3UI. Nucleotide distribution analysis showed that 5UI distribution is biased at both ends of 5′UTR whiles 3UI distribution is biased close to the start site of 3′UTR. Cis- elements analysis revealed that 5UI and 3UI sequences were rich of promoter-enhancing related elements, indicating that they might function in regulating the expression through them. Function enrichment analysis revealed that genes containing 5UI are significantly enriched in the RNA transport pathway. While, genes containing 3UI are significantly enriched in splicesome. Notably, many pentatricopeptide repeat-containing protein genes and the disease resistance genes were identified to be 3UI-containing. RT-PCR result confirmed the existence of UIs in the eight selected gene transcripts whereas alternative splicing events were found in some of them. Meanwhile, qRT-PCR result showed that UIs were differentially expressed among organs, and significant correlation was found between some genes and their UIs, for example: The expression of VPS28 and its 3UI was significantly negative correlated. This is the first report about the UIs in sweet orange from genome-wide level, which could provide evidence for further understanding of the role of UIs in gene expression regulation.
Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients
Authors: Enomoto Hirayuki , Aizawa Nobuhiro , Hasegawa Kunihiro , Ikeda Naoto , Sakai Yoshiyuki , Yoh Kazunori , Takata Ryo , Yuri Yukihisa , Kishino Kyohei , Shimono Yoshihiro , Ishii Noriko , Takashima Tomoyuki , Nishimura Takashi , Nishikawa Hiroki , Iwata Yoshinori , Iijima Hiroko , Nishiguchi Shuhei
Published: April 2020

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0 × 10−4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.
Inhibitors of DNA Glycosylases as Prospective Drugs
Authors: Mechetin Grigory V. , Endutkin Anton V. , Diatlova Evgeniia A. , Zharkov Dmitry O.
Published: April 2020

DNA glycosylases are enzymes that initiate the base excision repair pathway, a major biochemical process that protects the genomes of all living organisms from intrinsically and environmentally inflicted damage. Recently, base excision repair inhibition proved to be a viable strategy for the therapy of tumors that have lost alternative repair pathways, such as BRCA-deficient cancers sensitive to poly(ADP-ribose)polymerase inhibition. However, drugs targeting DNA glycosylases are still in development and so far have not advanced to clinical trials. In this review, we cover the attempts to validate DNA glycosylases as suitable targets for inhibition in the pharmacological treatment of cancer, neurodegenerative diseases, chronic inflammation, bacterial and viral infections. We discuss the glycosylase inhibitors described so far and survey the advances in the assays for DNA glycosylase reactions that may be used to screen pharmacological libraries for new active compounds.
New Technique in Assessment of Heart Chambers Remodeling in Acquired Mitral Valve Defects
Authors: Bokeria Leo , Makarenko Vladimir , Kosareva Tatiana
Published: April 2020

Objective: Analysis and presentation of the capabilities of the new ultrasound technique —the index of volume remodeling (IRV), which allows comprehensive assessing of pathological remodeling of the heart as an integrated functional anatomical system. Materials and methods: For this study 316 patients with acquired mitral valve disease (MVD) were examined prior to and following mitral valve replacement with bileaflet, disc-, and bioprostheses. Key parameters of the heart were measured in classical echocardiographic projections (end systolic area, end-diastolic area, end systolic volume, and end diastolic volume of ventricles, ventricular ejection fraction, atrial volume, and the ratio of ventricular to atrial volumes). The patients were examined 1–2 days prior to and following the surgery—before discharge, 6 months later, 1 year later, and then annually within next 5 years. The examination data were collected in one- and two-dimensional modes by using Philips EpiQ-7, iE33, HDI, Siemens Acuson, and HP Sonos 2500 diagnostic ultrasound machines equipped with 2.5 and 3.5 MHz transthoracic sensors. Results: A comprehensive study of structural geometric remodeling parameters of heart cavities in the context of acquired MVD allowed identifying new patterns in changes of the heart chambers geometry. These changes are reflected in the IRV, a digital indicator of the severity of cardiac pathological remodeling. Analysis of the dynamics of post-operative vs. pre-operative IRV-based remodeling data also showed that the index is highly sensible to the hemodynamic features of through-flows in various designs of prostheses. The IRV has a pronounced prognostic power and allows predicting the long-term outcome of surgical treatment with an accuracy of 82.35%. Conclusions: The IRV predictive accuracy formed the basis of the original classification of types of cardiac remodeling, which can assist both in determining the optimal timing for surgery, and in conjunction with other clinical diagnostic data, in predicting the long-term outcome of heart geometry restoration depending on the type of surgical correction. The IRV can be used in evaluation of the heart geometry for any cardiac pathology. It makes the approach to the analysis of pathological remodeling of the heart understandable, consistent, and universal, and also opens up opportunities for further expanding the diagnostic capabilities of radiology in cardiac surgery at all stages of the diagnostic process.
Polygenic Score for Body Mass Index Is Associated with Disordered Eating in a General Population Cohort
Authors: Abdulkadir Mohamed , Herle Moritz , De Stavola Bianca L. , Hübel Christopher , Santos Ferreira Diana L. , Loos Ruth J. F. , Bryant-Waugh Rachel , Bulik Cynthia M. , Micali Nadia
Published: April 2020

Background: Disordered eating (DE) is common and is associated with body mass index (BMI). We investigated whether genetic variants for BMI were associated with DE. Methods: BMI polygenic scores (PGS) were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8654) and their association with DE tested. Data on DE behaviors (e.g., binge eating and compensatory behaviors) were collected at ages 14, 16, 18 years, and DE cognitions (e.g., body dissatisfaction) at 14 years. Mediation analyses determined whether BMI mediated the association between the BMI-PGS and DE. Results: The BMI-PGS was positively associated with fasting (OR = 1.42, 95% CI = 1.25, 1.61), binge eating (OR = 1.28, 95% CI = 1.12, 1.46), purging (OR = 1.20, 95% CI = 1.02, 1.42), body dissatisfaction (Beta = 0.99, 95% CI = 0.77, 1.22), restrained eating (Beta = 0.14, 95% CI = 0.10, 1.17), emotional eating (Beta = 0.21, 95% CI = 0.052, 0.38), and negatively associated with thin ideal internalization (Beta = −0.15, 95% CI = −0.23, −0.07) and external eating (Beta = −0.19, 95% CI = −0.30, −0.09). These associations were mainly mediated by BMI. Conclusions: Genetic variants associated with BMI are also associated with DE. This association was mediated through BMI suggesting that weight potentially sits on the pathway from genetic liability to DE.
Fracture Resistance of Zirconia-Reinforced Lithium Silicate Ceramic Crowns Cemented with Conventional or Adhesive Systems: An In Vitro Study
Authors: D’Addazio Gianmaria , Santilli Manlio , Rollo Marco Lorenzo , Cardelli Paolo , Rexhepi Imena , Murmura Giovanna , Al-Haj Husain Nadin , Sinjari Bruna , Traini Tonino , Özcan Mutlu , Caputi Sergio
Published: April 2020

In recent years, Zirconia-reinforced Lithium Silicate ceramic (ZLS), combining lithium-silicate and zirconia features, has shown to have excellent mechanical and aesthetic characteristics. Thus, the aim of this study was to compare the fracture strength of ZLS single crowns cemented with two different cementation techniques. Twenty crowns were realised and cemented on teeth replicas achieved from an extracted premolar human tooth. The samples were divided into two groups of 10 specimens each, Glass-ionomeric cement (GIC) group and Self-Adhesive Resin Cement (ARC) group. The mechanical test was performed using a universal testing machine. The specimens were then evaluated with a scanning electron microscope (SEM) to identify for all crowns and related abutments the pattern of fracture after the breaking point. The data obtained were statistically analysed. The mean fracture toughness values and standard deviations (±SD) were 2227 ± 382 N and 3712 ± 319 N respectively for GIC and ARC groups. In fact, t-test showed a statistically significant difference between the two groups (p < 0.001). Moreover, the SEM results demonstrated portions of abutments still attached to the crown fragments in the ARC group, whilst these were not present in the GIC group. Within the limitations of this study, these results suggest the use of adhesive cementation for ZLS crowns, which significantly increase the compressive strength of ZLS restorations compared to GIC.