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29 pages, 8354 KiB  
Article
JRM-28, a Novel HDAC2 Inhibitor, Upregulates Plasticity-Associated Proteins in Hippocampal Neurons and Enhances Morphological Plasticity via Activation of CREB: Implications for Alzheimer’s Disease
by A. F. M. Towheedur Rahman, Sarojini Bulbule, Jawad Bin Belayet, Anna Benko, Carl Gunnar Gottschalk, David N. Frick, Leggy A. Arnold, M. Mahmun Hossain and Avik Roy
Cells 2024, 13(23), 1964; https://doi.org/10.3390/cells13231964 (registering DOI) - 27 Nov 2024
Abstract
Enhancement of neuronal plasticity by small-molecule therapeutics protects cognitive skills and also ameliorates progressive neurodegenerative pathologies like Alzheimer’s disease (AD) and dementia. One such compound, a novel histone deacetylase 2 (HDAC2) inhibitor named JRM-28, was shown here to enhance dendritic strength, augment spine [...] Read more.
Enhancement of neuronal plasticity by small-molecule therapeutics protects cognitive skills and also ameliorates progressive neurodegenerative pathologies like Alzheimer’s disease (AD) and dementia. One such compound, a novel histone deacetylase 2 (HDAC2) inhibitor named JRM-28, was shown here to enhance dendritic strength, augment spine density, and upregulate post-synaptic neurotransmission in hippocampal neurons. The molecular basis for this effect correlates with JRM-28-induced upregulation of the transcription of cAMP response element-binding protein(CREB), induction of its transcriptional activity, and subsequent stimulation of expressions of CREB-dependent plasticity-associated genes, such as those encoding N-methyl-D-aspartate (NMDA) receptor subunit NR2A and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1. Specifically, JRM-28 stimulated the NMDA- and AMPA-receptor-sensitive ionotropic calcium influx in hippocampal neurons. Interestingly, JRM-28 did not induce NMDA- and AMPA-sensitive calcium influx in hippocampal neurons once the expression of CREB was knocked down by creb siRNA, suggesting the critical role of CREB in JRM-28-mediated upregulation of synaptic plasticity. Finally, JRM-28 upregulated CREB mRNA, CREB-dependent plasticity-associated markers, and ionotropic calcium influx in iPSC-derived AD human neurons, indicating its therapeutic implications in the amelioration of AD pathologies. Full article
(This article belongs to the Special Issue Small Molecular Therapeutics Promoting Neuronal Plasticity, Hippocampal Learning, and Memory)
15 pages, 611 KiB  
Article
Non-Susceptibility Gene Variants in Head and Neck Paragangliomas
by Anastasiya V. Snezhkina, Vladislav S. Pavlov, George S. Krasnov, Dmitry V. Kalinin, Elena A. Pudova, Olga V. Stolbovskaya, Anastasiya V. Dunshina, Maria S. Fedorova and Anna V. Kudryavtseva
Int. J. Mol. Sci. 2024, 25(23), 12762; https://doi.org/10.3390/ijms252312762 (registering DOI) - 27 Nov 2024
Abstract
Head and neck paragangliomas (HNPGLs) are rare neoplasms that, along with pheochromocytomas and extra-adrenal paragangliomas, are associated with inherited mutations in at least 12 susceptibility genes in approximately 40% of cases. However, due to the rarity of HNPGLs, only a series of small-scale [...] Read more.
Head and neck paragangliomas (HNPGLs) are rare neoplasms that, along with pheochromocytomas and extra-adrenal paragangliomas, are associated with inherited mutations in at least 12 susceptibility genes in approximately 40% of cases. However, due to the rarity of HNPGLs, only a series of small-scale studies and individual cases have reported mutations in additional genes that may be involved in tumorigenesis. Consequently, numerous disease-causing mutations and genes responsible for the pathogenesis of HNPGLs remain poorly investigated. The aim of this study was to gain a deeper understanding of the genetic basis of HNPGLs by focusing on variants in genes that were not previously identified as well-known drivers. A whole-exome data analysis was conducted on a representative set of 152 HNPGLs. In 30% of the tumors examined, 53 potentially deleterious variants were identified in 36 different genes. The analysis identified pathogenic or likely pathogenic variants in the ARNT, IDH2, L2HGDH, MYH3, PIK3CA, and TERT genes. A functional network analysis of the mutated genes revealed numerous associations and a list of metabolic pathways (e.g., the TCA cycle, carbon metabolism, pyruvate metabolism, etc.) and signaling pathways (e.g., HIF1, PI3K-Akt, FoxO, AMPK, MAPK, etc.) that may play an important role in the development of HNPGLs. The identified range of genetic alterations affecting multiple genes and, potentially, influencing diverse cellular pathways provides an enhanced molecular genetic characterization of HNPGLs. Full article
(This article belongs to the Special Issue Genetic Mutations in Health and Disease)
36 pages, 7794 KiB  
Article
Video Games in Civic Engagement in Urban Planning, a Methodology for Effective and Informed Selection of Games for Specific Needs
by Jan Szot
Sustainability 2024, 16(23), 10411; https://doi.org/10.3390/su162310411 (registering DOI) - 27 Nov 2024
Abstract
Video games are recognized as significant tools and mediums to be used in civic participation in spatial planning and fostering local communities. As the phenomenon is widely recognized in papers presenting singular case studies and broader analyses in the field, selecting such serious [...] Read more.
Video games are recognized as significant tools and mediums to be used in civic participation in spatial planning and fostering local communities. As the phenomenon is widely recognized in papers presenting singular case studies and broader analyses in the field, selecting such serious games with certain characteristics remains unclear. The informed process of choosing games with particular properties regarding genesis, graphic style, genre, and complexity as the response for specified needs and process assumptions appears to be supportive in preventing unnecessary costs and data overproduction. Such avoidance is an important part of sustainable digital transformation. Therefore, there is a need for a more conscious process of selecting video games to be used in a participatory process. The following paper aims to propose a numerical base for a decisional instrument that could be useful for specifying the characteristics of games to be utilized in participation. They performed a multicriteria analysis of documented cases of implementing video games in civic engagement, allowing the creation of a set of numeric indicators that help determine the properties of games that will be most appropriate for given process assumptions. Such a tool can prevent overproducing data on the one hand and may cause dissemination of the presented way of handling the participation process on the other. Full article
(This article belongs to the Special Issue Co-creating the Future of Cities with Games: New Technologies and Methods for Sustainable and Smart City Planning)
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15 pages, 1053 KiB  
Article
Media Matters: How Information Release Shapes Monkeypox Vaccination Willingness
by Huan Wang and Nan Wu
Journal. Media 2024, 5(4), 1802-1816; https://doi.org/10.3390/journalmedia5040109 - 27 Nov 2024
Abstract
Background/Objectives: Despite the growing body of evidence addressing the reasons behind vaccine hesitancy, the positive role of media as a key environmental factor influencing vaccination, as well as its function in publicizing and encouraging vaccination, has been less thoroughly explored; Methods: This [...] Read more.
Background/Objectives: Despite the growing body of evidence addressing the reasons behind vaccine hesitancy, the positive role of media as a key environmental factor influencing vaccination, as well as its function in publicizing and encouraging vaccination, has been less thoroughly explored; Methods: This study focuses on the context of the current Monkeypox epidemic, examining the influence of media release channels and message framing on the public’s willingness to receive the Monkeypox vaccine. The findings are empirically validated through a survey experiment conducted in China; Results: The study reveals that both media channels—traditional TV media, official online media, and user-generated media—and media content framings, specifically thematic and episodic, significantly impact the public’s willingness to be vaccinated against Monkeypox. Notably, in the context of this public health event, individuals were more inclined to trust the episodic framing of traditional TV media and the thematic framing of official online media. Compared to thematic framing, episodic framing generally enhances respondents’ willingness to vaccinate. Furthermore, user-generated media exhibited a more negative effect on vaccination intentions during the Monkeypox epidemic, particularly when combined with episodic framing. Heterogeneity analysis indicated a significant difference in the effectiveness of official online media based on audience identity (student vs. non-student), with the student group showing a preference for official online media channels; Conclusions: The findings underscore the importance of public health communication in carefully selecting media release types and message framings. Additionally, it is crucial to consider audience heterogeneity and to employ differentiated communication methods to enhance the effectiveness of vaccine promotion. Full article
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18 pages, 295 KiB  
Article
Improved Hille-Type and Ohriska-Type Criteria for Half-Linear Third-Order Dynamic Equations
by Taher S. Hassan, Mnaouer Kachout, Bassant M. El-Matary, Loredana Florentina Iambor, Ismoil Odinaev and Akbar Ali
Mathematics 2024, 12(23), 3740; https://doi.org/10.3390/math12233740 (registering DOI) - 27 Nov 2024
Abstract
In this paper, we examine the oscillatory behavior of solutions to a class of half-linear third-order dynamic equations with deviating arguments [...] Read more.
In this paper, we examine the oscillatory behavior of solutions to a class of half-linear third-order dynamic equations with deviating arguments α2(η)ϕδ2α1ηϕδ1uΔ(η)ΔΔ+p(η)ϕδu(g(η))=0, on an arbitrary unbounded-above time scale T, where η∈[η0,∞)T:=[η0,∞)∩T, η0≥0, η0∈T and ϕζ(w):=wζsgnw, ζ>0. Using the integral mean approach and the known Riccati transform methodology, several improved Hille-type and Ohriska-type oscillation criteria have been derived that do not require some restrictive assumptions in the relevant results. Illustrative examples and conclusions show that these criteria are sharp for all third-order dynamic equations compared to the previous results in the literature. Full article
(This article belongs to the Special Issue Mathematical Modeling and Simulation of Oscillatory Phenomena, 2nd Edition)
16 pages, 334 KiB  
Article
COVID-19 Testing Behavior as a Predictor of COVID-19 Vaccination in Southeastern Louisiana: A Longitudinal Cohort Study
by Sara Al-Dahir, Saba Barri, Klaus Heyer, Ashley M. Taylor, Ala’a Khalil, Mohamed Belkhouche, Ibrahim Hamed, Liliana Cosenza, Malack Jwayyed, Malaak Saad, Tina Gerard, Leslie S. Craig, Daniel F. Sarpong and Daniel Salmon
Vaccines 2024, 12(12), 1338; https://doi.org/10.3390/vaccines12121338 (registering DOI) - 27 Nov 2024
Abstract
Background: Global COVID-19 vaccination effort faces the challenges of vaccine hesitancy and resistance, rooted in misinformation and institutional distrust. Addressing these barriers with customized messaging is essential, yet the relationship between vaccine hesitancy and other health-seeking behaviors, like COVID-19 testing, has been underexplored. [...] Read more.
Background: Global COVID-19 vaccination effort faces the challenges of vaccine hesitancy and resistance, rooted in misinformation and institutional distrust. Addressing these barriers with customized messaging is essential, yet the relationship between vaccine hesitancy and other health-seeking behaviors, like COVID-19 testing, has been underexplored. Method: This study assessed COVID-19 vaccine uptake in Southeastern Louisiana across 10 pharmacies and clinics in areas with historically high rates of COVID-19 infection. Using a longitudinal cohort design from Fall 2022 through Fall 2023, a total of 377 participants from diverse backgrounds were surveyed while seeking routine care at partner organizations. Baseline data was collected on demographics, vaccine knowledge, attitudes, and test-seeking behaviors. Information on COVID-19 testing and vaccination were self-reported and verified, as applicable, in the patient’s medical records. All data was analyzed using descriptive statistics, log-binomial to yield risk ratios, and an ordinal logistic regression for vaccine series completion. Results: Among the 377 participants, 207 were unvaccinated while 170 received the vaccine. Among the unvaccinated individuals, 53 received a half-dose, 97 a full dose, and 14 a booster. Notably, 75% of unvaccinated and 89% of vaccinated participants underwent COVID-19 testing. Individuals who were tested were 1.71 times more likely to be vaccinated (95% CI 1.03, 2.84), while previous vaccine refusal was associated with lower vaccine acceptance (0.77; 95% CI 0.54, 1.09). In the bivariate and multivariate analysis, COVID-19 testing behavior was positively associated with COVID-19 vaccine uptake. Conclusion: Exploring the connection between COVID-19 testing and vaccination provides valuable insights for future public health messaging to mitigate vaccine hesitancy. Full article
(This article belongs to the Special Issue Advance Public Health through Vaccination)
14 pages, 3594 KiB  
Article
The Prevalence of Egg Parasitoids of Two Cobweb Spiders in a Tropical Urban Gradient
by Natalia Jiménez-Conejo, Paul E. Hanson, Eduardo Chacón-Madrigal and Geovanna Rojas-Malavasi
Arthropoda 2024, 2(4), 250-263; https://doi.org/10.3390/arthropoda2040018 - 27 Nov 2024
Abstract
Parasitoidism strongly influences the structure of the spiders’ populations, and it can be affected by environmental factors such as those caused by anthropogenic actions. We studied the prevalence of parasitoids in egg sacs and the proportion of eggs parasitized in each egg sac [...] Read more.
Parasitoidism strongly influences the structure of the spiders’ populations, and it can be affected by environmental factors such as those caused by anthropogenic actions. We studied the prevalence of parasitoids in egg sacs and the proportion of eggs parasitized in each egg sac of two synanthropic spider species, one native to the American continent (Parasteatoda tepidariorum) and another recently introduced to the Americas (Latrodectus geometricus). We conducted the study at two scales, along an urban gradient (from highly urbanized to rural sites) and in the vegetation surrounding each sampling site (microscale). We expected to find a larger prevalence of parasitoids in the most urbanized sites and around sampling sites with more vegetation. However, we saw more parasitized egg sacs at the intermediate urbanized site for both species, and the vegetation surrounding the sampling sites did not affect the number of parasitized egg sacs. Therefore, conditions in the site with intermediate urban development favored parasitoids. We also found more parasitized egg sacs in P. tepidariorum than in L. geometricus, which is likely a consequence of native parasites not being adapted to a new host. The proportion of eggs parasitized was similar for both species in all sites, which may be related to the behavior (e.g., searching behavior) and number of spider eggs a female parasitoid can parasitize. Full article
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14 pages, 456 KiB  
Article
Evaluating the Impact of STEM Academic Interventions on College Readiness for Rural Students
by Janet B. Walton, Toni A. May and Carla C. Johnson
Trends High. Educ. 2024, 3(4), 1017-1030; https://doi.org/10.3390/higheredu3040059 - 27 Nov 2024
Abstract
This study used a quasi-experimental cohort approach to investigate the impact of early academic interventions on rural students’ academic college readiness as measured by indicators of science, mathematics, and English language proficiency in the United States. The program, delivered by a higher education [...] Read more.
This study used a quasi-experimental cohort approach to investigate the impact of early academic interventions on rural students’ academic college readiness as measured by indicators of science, mathematics, and English language proficiency in the United States. The program, delivered by a higher education institution, implemented a range of academic supports for students, including tutoring and in-class and after-school support by credentialed instructors, with the aim of preparing students for success in secondary and post-secondary educational experiences. The American College Testing (ACT) Aspire scores in science, mathematics, English language comprehension, and reading for a cohort of 8th-grade students in their second year of program participation (n = 100) were compared to the scores of a cohort of non-participants (n = 86) from the same school. Students who had participated in the program were significantly more likely than non-participants to meet college readiness benchmarks in all content areas and scored significantly higher than the non-program cohort in terms of their average percentile ranks. More research is needed to understand how particular interventions or combinations of interventions implemented in middle school impact students’ college readiness. Full article
(This article belongs to the Special Issue STEM in Higher Education)
17 pages, 753 KiB  
Systematic Review
The Role of 11C-Methionine PET Imaging for the Evaluation of Lymphomas: A Systematic Review
by Francesco Dondi, Maria Gazzilli, Gian Luca Viganò, Antonio Rosario Pisani, Cristina Ferrari, Giuseppe Rubini and Francesco Bertagna
Hematol. Rep. 2024, 16(4), 752-768; https://doi.org/10.3390/hematolrep16040072 - 27 Nov 2024
Abstract
Background: In the last years, different evidence has underlined a possible role for [11C]-methionine ([11C]MET) positron emission tomography (PET) imaging for the evaluation of lymphomas. The aim of this paper was, therefore, to review the available scientific literature focusing on this topic. [...] Read more.
Background: In the last years, different evidence has underlined a possible role for [11C]-methionine ([11C]MET) positron emission tomography (PET) imaging for the evaluation of lymphomas. The aim of this paper was, therefore, to review the available scientific literature focusing on this topic. Methods: A wide literature search of the PubMed/MEDLINE, Scopus and Cochrane Library databases was conducted in order to find relevant published articles investigating the role of [11C]MET in the assessment of lymphomas. Results: Eighteen studies were included in the systematic review and the main fields of application of this imaging modality were the evaluation of disease, therapy response assessment, prognostic evaluation and differential diagnosis with other pathological conditions. Conclusion: Even with heterogeneous evidence, a possible role for [11C]MET PET imaging in the assessment of lymphomas affecting both the whole body and the central nervous system was underlined. When compared to [18F]fluorodesoxyglucose ([18F]FDG) imaging, in general, similar results have been reported between the two modalities in these settings. Full article
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19 pages, 1265 KiB  
Review
Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective
by Leslie Marisol Gonzalez-Hermosillo, Guillermo Cueto-Robledo, Dulce Iliana Navarro-Vergara, Maria Berenice Torres-Rojas, Marisol García-Cesar, Oscar Pérez-Méndez and Galileo Escobedo
Adv. Respir. Med. 2024, 92(6), 485-503; https://doi.org/10.3390/arm92060044 - 27 Nov 2024
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without [...] Read more.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease’s pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes. Full article
11 pages, 1123 KiB  
Article
Genetic Diversity and Gains from Selection for Fruit and Bean Physical Traits from the Conilon Coffee Genotype
by Jessica Rodrigues Dalazen, Rodrigo Barros Rocha, Gleison Oliosi, Larissa Fatarelli Bento de Araújo, Marcelo Curitiba Espindula, Weverton Pereira Rodrigues and Fabio Luiz Partelli
Int. J. Plant Biol. 2024, 15(4), 1266-1276; https://doi.org/10.3390/ijpb15040087 - 27 Nov 2024
Abstract
Plant breeding of Coffea canephora is based on the characterization and use of the natural genetic variability of the species. Thus, the objective of this study was to quantify the genetic diversity and gains from selection of the fruit and bean physical traits [...] Read more.
Plant breeding of Coffea canephora is based on the characterization and use of the natural genetic variability of the species. Thus, the objective of this study was to quantify the genetic diversity and gains from selection of the fruit and bean physical traits of the C. canephora plant, seeking to understand the relations among the yield components and identify genotypes with superior traits. For this purpose, 42 genotypes were evaluated over two crop years while considering a randomized block design in a factorial arrangement to quantify the effects of genotypes, crop years, and the interaction between these two factors. Coffee fruit samples in the cherry stage were used to evaluate the weights, volumes, and dimensions of the fresh fruit and beans after drying. Genotypic variance prevailed over environmental variance for all of the fruit and bean physical traits of the coffee plants, except for the greatest fruit width (FWG). These associations indicate that the constituent parts of the fruit increased in a manner proportional to an increase in weight. Such associations can facilitate or hinder plant selection. The total gains obtained through the selection indices were similar to those obtained through direct selection for greater bean weights. However, the use of selection indices made it possible to identify clones with more balanced traits. Full article
(This article belongs to the Section Plant Biochemistry and Genetics)
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16 pages, 1923 KiB  
Article
Optimizing the Genetic Transformation of Coffea arabica Using Agrobacterium tumefaciens
by Diana Molina and Ricardo Acuña
Int. J. Plant Biol. 2024, 15(4), 1250-1265; https://doi.org/10.3390/ijpb15040086 - 27 Nov 2024
Abstract
The genetic transformation of Coffea arabica L. is an alternative strategy for obtaining plants with agronomic traits of interest that is less time-consuming than conventional breeding methods. Given the importance of coffee cultivation in Colombia, this study evaluated the main factors interfering with [...] Read more.
The genetic transformation of Coffea arabica L. is an alternative strategy for obtaining plants with agronomic traits of interest that is less time-consuming than conventional breeding methods. Given the importance of coffee cultivation in Colombia, this study evaluated the main factors interfering with the genetic transformation of C. arabica using Agrobacterium tumefaciens. An efficient and reproducible method was accordingly developed that involved propagating “early” embryogenic calli in a liquid proliferation medium supplemented with 3 mg L−1 BAP for eight months, followed by sonication for 300 s in a suspension of LBA4404 OD600 of 0.5, harboring pCambia1301, and then incubation in this same suspension for 1 h. The vector pCambia1301 contained the uidA gene under control of the 35S promoter. A micropipette was used to remove the Agrobacterium suspension from the embryogenic callus. The remaining Agrobacterium suspension was blotted off by placing the embryogenic callus on filter paper. The embryogenic callus was then co-cultured for four days in a solid differentiation medium supplemented with 100 µM acetosyringone on filter paper. Subsequently, the embryogenic callus was post-cultured for four days in liquid differentiation medium under constant shaking at 100 rpm with 300 mg L−1 Cefotaxime, followed by selection with 50 mg L−1 hygromycin at 26 °C in the dark, with subcultures at 20-day intervals until somatic embryos were formed for subsequent culturing in germination medium. Molecular analysis confirmed the presence of the uidA gene in coffee seedlings transformed with strains LBA4404 and EHA105 and vectors pCambia1301 and pCambia2301 by polymerase chain reaction (PCR) analysis. This method successfully enables the stable integration of genes of interest in the coffee plant genome. Full article
(This article belongs to the Section Plant Reproduction)
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10 pages, 210 KiB  
Article
Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database
by Connor Frey
Pharmacoepidemiology 2024, 3(4), 373-382; https://doi.org/10.3390/pharma3040026 - 27 Nov 2024
Abstract
Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and [...] Read more.
Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and cardiovascular adverse events. It evaluated men treated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors from 2003 to 2023. This study included patients treated with leuprolide, goserelin, triptorelin, degarelix, relugolix, bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, enzalutamide, olaparib, rucaparib, talazoparib, and niraparib. The main outcome measure was the reported odds ratio (ROR) of adverse cardiovascular event associated with these treatments. Results: Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified. Leuprolide (ROR 0.481, 95% CI: 0.423–0.547), triptorelin (ROR 0.527, 95% CI: 0.305–0.909), enzalutamide (ROR 0.393, 95% CI: 0.341–0.452), and olaparib (ROR 0.145, 95% CI: 0.054–0.386) reduced the risk of myocardial infarction. Goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI: 1.367–3.654). Degarelix and relugolix both increased the risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497), and enzalutamide was associated with an increased risk of heart failure (ROR 1.305, 95% CI: 1.135–1.501). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622) and heart failure (ROR 3.730, 95% CI: 3.085–4.510). Niraparib increased the risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092). Conclusions: These findings underscore the need for clinicians to monitor cardiac complications in patients undergoing these therapies. Full article
(This article belongs to the Topic Advance in Cancer Pharmacoepidemiology)
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13 pages, 3333 KiB  
Article
Microplastic Interference with Fipronil Toxicity to Zebrafish Embryonic Development
by Flavio Kiyoshi Tominaga, Rafaella Silva Brito, Isis Wanessa Ferreira dos Santos, Amanda de Azevedo Valle, Gisele Giannocco, Rui Monteiro de Barros Maciel, Fábio Kummrow, Marilia Cristina Oliveira Souza, Ana Carolina Luchiari and Bruno Fiorelini Pereira
Microplastics 2024, 3(4), 717-729; https://doi.org/10.3390/microplastics3040044 - 27 Nov 2024
Abstract
Environmental contamination from mixtures of chemical substances and materials resulting from anthropogenic activities has adverse effects on aquatic biota. Fipronil (FP) is an insecticide widely used in agriculture and public health and is frequently detected in environmental compartments. Microplastics (MPs) represent another class [...] Read more.
Environmental contamination from mixtures of chemical substances and materials resulting from anthropogenic activities has adverse effects on aquatic biota. Fipronil (FP) is an insecticide widely used in agriculture and public health and is frequently detected in environmental compartments. Microplastics (MPs) represent another class of contaminants that have raised concerns due to their ability to adsorb pollutants, potentially acting as a vector. This study evaluated the influence of polyethylene microplastics on the toxicity of FP in zebrafish (Danio rerio) embryos/larvae. Zebrafish embryos were exposed to aqueous suspension containing purified FP and the FP + MP mixtures for 120 h. Mortality, teratogenicity and cardiotoxicity were observed during the zebrafish development. Larvae were more sensitive to FP than the embryo. The presence of MPs reduced lethality; however, no significant changes were observed for sublethal endpoints. Our findings demonstrate the acute impact of FP on zebrafish embryos/larvae, demonstrating that MPs interfere with toxicity. Therefore, understanding the mechanisms of interaction between contaminants of different classes is essential for predicting the associated risks to biota. Full article
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24 pages, 3042 KiB  
Article
Exploring the Role of News Outlets in the Rise of a Conspiracy Theory: Hydroxychloroquine in the Early Days of COVID-19
by Robert Dickinson, Dominique Makowski, Harm van Marwijk and Elizabeth Ford
COVID 2024, 4(12), 1873-1896; https://doi.org/10.3390/covid4120132 - 27 Nov 2024
Abstract
Improper use of hydroxychloroquine to treat COVID-19 has been linked to 17,000 preventable deaths. This content analysis study investigates the emergence of this conspiracy theory, the role of the news media in perpetuating and disseminating it, and whether coverage differed by outlet political [...] Read more.
Improper use of hydroxychloroquine to treat COVID-19 has been linked to 17,000 preventable deaths. This content analysis study investigates the emergence of this conspiracy theory, the role of the news media in perpetuating and disseminating it, and whether coverage differed by outlet political alignment. We searched Nexis for relevant media from 17–31 March 2020. A total of 128 media pieces were coded qualitatively and thematically analysed. The news media amplified the voices of right-wing political elites and used a variety of manipulative tactics in reporting on hydroxychloroquine. Powerful ingroup/outgroup mechanisms polarised the American public and created a schism between Trump supporters and the public health apparatus that reflected the political asymmetry in reporting on hydroxychloroquine. The widespread use of optimistic framings and anecdotal evidence contributed to public misunderstandings of the evidence. Therefore, strategic and interventionist public health efforts are required to combat misinformation. This study informs discussions of how politicised media coverage catalyses conspiracism. Full article
(This article belongs to the Special Issue COVID and Public Health)
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27 pages, 6682 KiB  
Article
Reflecting on City Governmental Responses to COVID-19: Focus on Design Justice
by Joongsub Kim and Stephen Vogel
Architecture 2024, 4(4), 1071-1097; https://doi.org/10.3390/architecture4040056 - 27 Nov 2024
Abstract
In the early stages of the COVID-19 pandemic and the resultant stay-at-home mandates, local governments in some cities in the United States implemented programs in response to the pandemic. This article focuses on Slow Streets, which were several programs implemented in eleven cities [...] Read more.
In the early stages of the COVID-19 pandemic and the resultant stay-at-home mandates, local governments in some cities in the United States implemented programs in response to the pandemic. This article focuses on Slow Streets, which were several programs implemented in eleven cities (Los Angeles, Oakland, San Francisco, Seattle, Portland, Denver, Chicago, Minneapolis, Detroit, Boston, and New York) in the United States. The programs were intended to keep people healthy by providing temporary public spaces on residential roads where residents were allowed to exercise and socialize. Some practitioners characterized the programs as tactical urbanism or tactical placemaking and as agile responses to the public health crisis. The programs deserve a critical reflection, considering their potential impact on community health and the limited amount of the literature on the program in terms of design justice, which is an approach to design that prioritizes marginalized communities and challenges their structural inequality. This reflective study attempts to fill that gap in the literature of architecture and urban design. This article aims to examine whether the Slow Streets programs promoted design justice. To address that aim, we propose a social justice framework to evaluate the program, because social justice is essential to design justice. Data from publicly available information online about the eleven cities’ Slow Streets programs, interviews, surveys, focus groups, and the interdisciplinary literature support the qualitative research. The study outcomes suggest that the Slow Streets program had limited success because their attention to the priorities of underserved populations was ineffective. We argue that while the programs provided a timely response to the pandemic, the programs did not adequately address the vulnerability of low-income communities of color due to the limited consideration of design justice. Building on the lessons from social justice and human geography, the article concludes with recommendations for future practices including place-cultivating and human geography-informed design to better serve vulnerable communities of color. Full article
(This article belongs to the Special Issue Reconsidering Design Justice in Architecture and Urban Design in the Post-pandemic Era)
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14 pages, 4258 KiB  
Article
Assessing Acute Pericarditis with T1 Mapping: A Supportive Contrast-Free CMR Marker
by Riccardo Cau, Francesco Pisu, Roberta Montisci, Tommaso D’Angelo, Cesare Mantini, Rodrigo Salgado and Luca Saba
Tomography 2024, 10(12), 1881-1894; https://doi.org/10.3390/tomography10120137 - 27 Nov 2024
Abstract
Objective: The purpose of this study was to explore the impact of pericardial T1 mapping as a potential supportive non-contrast cardiovascular magnetic resonance (CMR) parameter in the diagnosis of acute pericarditis. Additionally, we investigated the relationship between T1 mapping values in acute pericarditis [...] Read more.
Objective: The purpose of this study was to explore the impact of pericardial T1 mapping as a potential supportive non-contrast cardiovascular magnetic resonance (CMR) parameter in the diagnosis of acute pericarditis. Additionally, we investigated the relationship between T1 mapping values in acute pericarditis patients and their demographic data, cardiovascular risk factors, clinical parameters, cardiac biomarkers, and cardiac function. Method: This retrospective study included CMR scans in 35 consecutive patients with acute pericarditis (26 males, 45.54 ± 23.38 years). Moreover, we included 17 sex- and age-matched healthy controls (12 males, mean age 47.78 ±19.38 years). CMR-derived pericardial T1 mapping values, which included all pericardial structures within the pericardial layers—encompassing both pericardial effusion and pericardial layer thickness—were analyzed and compared between acute pericarditis patients and controls. Results: Compared to the matched control group, acute pericarditis patients demonstrated significantly lower pericardial T1 mapping values (2137 ms ± 519 vs. 3268 ms ± 362, p = 0.001). In the multivariable analysis, the pericardial T1 mapping value was independently associated with the severity of pericardial late gadolinium enhancement (LGE) (β coefficient = −3.271, p = 0.003). The receiver operating characteristic curve analysis showed that the diagnostic performance of pericardial T1 mapping in discriminating acute pericarditis patients was excellent, with an area under the curve of 0.97 (95% CI = 0.94–0.98), using a threshold of 2862.5 ms. Conclusions: Pericardial T1 mapping values could serve as an additional non-contrast CMR parameter for identifying patients with acute pericarditis, demonstrating an independent association with the severity of pericardial LGE. Full article
(This article belongs to the Section Cardiovascular Imaging)
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20 pages, 810 KiB  
Review
Sensitivity of Collagenolytic Periopathogenic Microorganisms to Chlorhexidine Solution: A Comprehensive Review of In Vitro Studies
by Bruno Barbosa, Filipe Castro, Jorge Pereira, Maria Catarino, Jaime Guimarães and Gustavo Vicentis Oliveira Fernandes
Microbiol. Res. 2024, 15(4), 2435-2454; https://doi.org/10.3390/microbiolres15040164 - 27 Nov 2024
Abstract
Objective: This review evaluated chlorhexidine (CHX)’s beneficial effect as an antibacterial substance on periodontopathogenic bacteria, which can influence the preservation of periodontal tissues and biomaterials. Methods: A search was performed in the PubMed/MedLine, B-On, ScienceDirect, and Cochrane Library databases. In vitro studies published [...] Read more.
Objective: This review evaluated chlorhexidine (CHX)’s beneficial effect as an antibacterial substance on periodontopathogenic bacteria, which can influence the preservation of periodontal tissues and biomaterials. Methods: A search was performed in the PubMed/MedLine, B-On, ScienceDirect, and Cochrane Library databases. In vitro studies published between 1 January 2000 and 31 December 2023 in the English language were included; studies that did not correlate the sensitivity of collagenolytic microorganisms to CHX and observational and in vivo studies were excluded. The Quality Assessment Tool for In Vitro Studies (QUIN) evaluated the risk of bias. Results: Eight studies were included; six assessed the inhibitory effect of CHX on the activity of various bacteria associated with periodontitis and collagen degradation; two studies evaluated the same effect only for P. gingivalis. All the studies had an evaluation percentage above 70%, representing a low bias risk. Conclusions: There is a relationship between collagen degradation and the microorganisms in periodontal diseases. CHX showed efficacy against various microorganisms, inhibiting their growth and cell viability. CHX demonstrated significant implications for preventing and treating infections associated with collagen degradation. Full article
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11 pages, 460 KiB  
Article
Evaluating the Impact of Maternal Lipid Profiles on Fetal Cardiac Function at Mid-Gestation: An Observational Study
by Biliana Belovan, Zoran Laurentiu Popa, Cosmin Citu, Ioana Mihaela Citu, Ioan Sas and Adrian Ratiu
Clin. Pract. 2024, 14(6), 2590-2600; https://doi.org/10.3390/clinpract14060204 - 27 Nov 2024
Abstract
Background: Maternal dyslipidemia during pregnancy may influence fetal cardiac development and function, potentially predisposing offspring to cardiovascular diseases later in life. This study aims to evaluate the relationship between maternal lipid profiles and fetal cardiac function at mid-gestation, utilizing detailed echocardiographic assessments. Methods: [...] Read more.
Background: Maternal dyslipidemia during pregnancy may influence fetal cardiac development and function, potentially predisposing offspring to cardiovascular diseases later in life. This study aims to evaluate the relationship between maternal lipid profiles and fetal cardiac function at mid-gestation, utilizing detailed echocardiographic assessments. Methods: In this prospective cohort study conducted at the Obstetrics and Gynecology Clinic of the Timișoara Municipal Emergency Hospital, 19 pregnant women aged 27–40 years were recruited and divided into two groups based on their triglyceride levels: Group A (triglycerides ≤ 150 mg/dL, n = 48) and Group B (triglycerides > 150 mg/dL, n = 28). Maternal demographic data and lipid profiles were recorded. Fetal echocardiographic measurements, including global longitudinal strain and ventricular function parameters, were obtained between 20 and 24 weeks of gestation. Statistical analyses, including subgroup comparisons, correlations, and regression analyses, were performed. Results: Maternal BMI was significantly higher in Group B compared to Group A (31.94 ± 2.80 vs. 27.01 ± 2.40 kg/m2, p < 0.001). Group B showed higher mean triglyceride levels (163.43 ± 11.34 mg/dL) compared to Group A (131.42 ± 10.57 mg/dL, p < 0.001). Fetal echocardiographic measurements indicated reduced global longitudinal strain in fetuses of Group B mothers (LV strain: −19.86% ± 6.83% vs. −26.14% ± 5.92%, p = 0.017). Significant correlations were found between maternal triglyceride levels and fetal LV strain (r = 0.536, p = 0.019). Regression analysis identified maternal triglyceride levels and BMI as significant predictors of reduced fetal LV strain (β = 0.45, p = 0.021 and β = 0.39, p = 0.038, respectively). Conclusions: Elevated maternal triglyceride levels, LDL cholesterol, and BMI are associated with altered fetal cardiac function parameters at mid-gestation, suggesting that maternal lipid profiles may impact fetal cardiac development. These findings underscore the importance of monitoring lipid levels during pregnancy and suggest potential benefits of managing dyslipidemia to improve fetal cardiac outcomes. However, the study included only a small sample; therefore, the study needs to be continued with a larger group. Full article
10 pages, 270 KiB  
Article
Clinical Success of Pulpotomies Using Intermediate Restorations and Preformed Metal Crowns in the Context of a Developing Country: A Retrospective Questionnaire-Based Investigation
by Ana Luisa Montero-Copoya, Norma Leticia Robles-Bermeo, Salvador Eduardo Lucas-Rincón, María de Lourdes Márquez-Corona, Saraí Carmina Guadarrama-Reyes, Nayeli Lovera-Rojas, Juan Fernando Casanova-Rosado, Juan José Villalobos-Rodelo, Mauricio Escoffié-Ramírez and Carlo Eduardo Medina-Solís
Clin. Pract. 2024, 14(6), 2580-2589; https://doi.org/10.3390/clinpract14060203 - 27 Nov 2024
Abstract
Background: Dental caries is one of the most prevalent dental illnesses in children. Untreated severe caries can damage teeth, requiring pulpotomy to save them. Objective: To evaluate the clinical success rate of treatments involving pulpotomies + IRM (Intermediate Restorative Material, composed of reinforced [...] Read more.
Background: Dental caries is one of the most prevalent dental illnesses in children. Untreated severe caries can damage teeth, requiring pulpotomy to save them. Objective: To evaluate the clinical success rate of treatments involving pulpotomies + IRM (Intermediate Restorative Material, composed of reinforced zinc oxide–eugenol polymers) + preformed metal crowns (PMCs) in primary teeth of children treated at a public university in Mexico. Materials and Methods: A cross-sectional ambispective study was conducted on children aged 10 years or younger, treated at a public university in Mexico. A total of 1281 medical records from February 2018 to June 2023 were reviewed, yielding a sample of 199 children treated with pulpotomy + IRM + PMC. Information was collected via telephone interviews with parents/caregivers to inquire about any symptoms following the pulpotomy and metal crown treatments. Success was defined as the absence of pain, inflammation, or infection. Results: During the study period, the number of teeth treated with pulpotomy + IRM + PMC was 414, with follow-ups ranging from 6 to 69 months. Most participants were girls (54.3%), while 45.7% were boys. Out of the 167 pulpotomy + IRM + PMC treatments included in the study, the clinical success rate was 98.2%. Conclusions: The clinical success rate of primary teeth treated with pulpotomy + IRM + PMCs was high, close to 100%, based on evidence and symptom reports from parents/caregivers. It would be beneficial to implement its use in public health institutions in countries such as Mexico. Full article
(This article belongs to the Special Issue New Trends, Materials, and Technologies and Consolidating Best Practices in Dentistry, 2nd Edition)
10 pages, 974 KiB  
Article
Beta-Alanine Supplementation for CrossFit® Performance
by Hannah Verity, Darren Candow and Philip D. Chilibeck
Nutraceuticals 2024, 4(4), 673-682; https://doi.org/10.3390/nutraceuticals4040037 - 27 Nov 2024
Abstract
This study aimed to investigate whether beta-alanine supplementation (BA) improves performance and rating of perceived exertion (RPE) and reduces the respiratory exchange ratio (RER) during a CrossFit® workout. Fourteen participants were randomized in a double-blind design to either BA or placebo, with [...] Read more.
This study aimed to investigate whether beta-alanine supplementation (BA) improves performance and rating of perceived exertion (RPE) and reduces the respiratory exchange ratio (RER) during a CrossFit® workout. Fourteen participants were randomized in a double-blind design to either BA or placebo, with 12 participants (7 males, 5 females, 32 ± 9.2 y) completing the study. Participants performed two tests, separated by three weeks of supplementing with either 6.4 g/day of BA or placebo. Performance tests involved time to complete an adapted CrossFit® “Fran” Workout of the Day: 21-15-9 repetition scheme alternating between dumbbell thrusters and kipping pull-ups. No significant differences between the BA group and the placebo group were observed for performance time improvement (−13.4 s vs. −12.9 s, p = 0.97), change in mean RER (0.06 vs. 0.05, p = 0.84), or change in RPE (10-point scale) (−0.4 vs. −0.07, p = 0.56). There was a group × time × time during test interaction for RER (p = 0.021). Compared to pre-testing, post-testing RER was higher at the 25% time point of the test for the BA group and at the 75% and 100% time points in the placebo group (p < 0.05). Beta-alanine did not show significant ergogenic effects during an adapted version of the CrossFit® workout “Fran”, although it might have helped with the buffering of acidity later in the test, based on RER. Full article
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9 pages, 963 KiB  
Commentary
Accuracy and Outcomes of Sentinel Lymph Node Biopsy in Male with Breast Cancer: A Narrative Review and Expert Opinion
by Calogero Cipolla, Vittorio Gebbia, Eleonora D’Agati, Martina Greco, Chiara Mesi, Giuseppa Scandurra, Daniela Sambataro and Maria Rosaria Valerio
Curr. Oncol. 2024, 31(12), 7566-7574; https://doi.org/10.3390/curroncol31120557 - 27 Nov 2024
Abstract
Male breast cancer (MBC) is a rare disease, accounting for less than 1% of all breast cancer cases. Sentinel lymph node biopsy (SLNB) has emerged as a less invasive alternative to axillary lymph node dissection (ALND) for axillary staging in breast cancer, offering [...] Read more.
Male breast cancer (MBC) is a rare disease, accounting for less than 1% of all breast cancer cases. Sentinel lymph node biopsy (SLNB) has emerged as a less invasive alternative to axillary lymph node dissection (ALND) for axillary staging in breast cancer, offering reduced morbidity and comparable accuracy. However, the application of SLNB in MBC remains underexplored, with limited male-specific data and treatment protocols often extrapolated from female breast cancer studies. Available evidence suggests that SLNB in men demonstrates high diagnostic accuracy, with low false-negative rates and a high sentinel lymph node identification rate. Despite this, there is ongoing debate about its long-term impact on clinical outcomes, particularly for patients with sentinel node metastasis, where ALND may still provide superior survival outcomes in some cases. Predictive tools are being developed to identify better patients who may benefit from SLNB alone, potentially reducing the need for more invasive procedures. As the role of SLNB continues to evolve in MBC management, further prospective research is needed to refine its application and assess its long-term oncologic outcomes. Full article
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9 pages, 2192 KiB  
Article
Multidisciplinary Approach of a Male Case of Imported Malaria, HIV Chronic Infection, and Latent Syphilis
by Rebeca Eunice García-Mendiola, Maritza Micheli García-Lucas, Jennifer Morales-Vázquez, Raúl Adrián Cruz-Flores, Miguel Ángel Loyola-Cruz, Clemente Cruz-Cruz, Emilio Mariano Durán-Manuel, Enzo Vásquez-Jiménez, Graciela Castro-Escarpulli, María de Jesús Sánchez-Guzmán, Victor Hugo Gutiérrez-Muñoz, Iliana Alejandra Cortés-Ortíz, Misael González-Ibarra, Juan Carlos Bravata-Alcántara, Jesús Alejandro Pineda-Migranas, Estibeyesbo Said Plascencia-Nieto, Carlos Alberto Jiménez-Zamarripa, Erika Gómez-Zamora, Claudia Camelia Calzada-Mendoza and Juan Manuel Bello-López
Infect. Dis. Rep. 2024, 16(6), 1118-1126; https://doi.org/10.3390/idr16060091 - 27 Nov 2024
Abstract
Background: The current economic and social crisis in Latin America has caused migration to the USA, bringing with it Public Health challenges due to the importation of various infectious diseases. Migrants, particularly those with chronic conditions, such as HIV infection and other sexually [...] Read more.
Background: The current economic and social crisis in Latin America has caused migration to the USA, bringing with it Public Health challenges due to the importation of various infectious diseases. Migrants, particularly those with chronic conditions, such as HIV infection and other sexually transmitted infections (STI), are at greater risk due to pharmacological interruption and access to medical care, so the timely detection of diseases acquired during their migration, such as malaria, is crucial to avoid health complications. Objective: To outline by a multidisciplinary approach (Infectology, Parasitology, Epidemiology, molecular Biology, Venereology, and Public Health) the diagnosis and management of a male case with malaria imported to Mexican territory, HIV chronic infection, and latent syphilis. Methods: A male migrant of Venezuelan nationality attended the Clínica Especializada Condesa Iztapalapa in Mexico City for health complications. A comprehensive analysis of laboratory and molecular tests was performed to confirm HIV infection. During the STI diagnostic algorithm, latent syphilis was detected and microscopic observation of blood smears revealed parasitic forms compatible with malaria. Standard and molecular tests were applied under the operational definition for malaria cases for identification, diagnosis, and treatment. Finally, study of clinical history and migration route by questioning for the investigation of the imported case was performed. Results: The immigrant was diagnosed with HIV chronic-stage infection with interrupted antiretroviral therapy (ART), latent syphilis, and malaria by Plasmodium vivax. The ART administered was chosen based on the possible drug interaction with antimalarials and genetic barrier to the HLA-B* allele. Finally, antimicrobial therapy against syphilis was penicillin. From the analysis of the migratory route, incubation time of imported malaria, and questioning, we speculated that the migrant acquired the P. vivax infection in Panama. Conclusions: This case highlights the complex health problems faced by migrants with HIV infection, particularly when they contract additional infections such as malaria during migration and highlights the need for comprehensive access to healthcare and ART, antimalarial and antimicrobial treatments to mitigate the health risks of this vulnerable population. Full article
(This article belongs to the Section Parasitological Diseases)
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19 pages, 1575 KiB  
Review
Soil Symphony: A Comprehensive Overview of Plant–Microbe Interactions in Agricultural Systems
by Arpitha Chatchatnahalli Tharanath, Raje Siddiraju Upendra and Karthik Rajendra
Appl. Microbiol. 2024, 4(4), 1549-1567; https://doi.org/10.3390/applmicrobiol4040106 - 27 Nov 2024
Abstract
The rhizosphere, a narrow region of soil surrounding plant roots, is an environment rich in microbial diversity that profoundly influences plants’ health, growth, and agricultural productivity. This microbial community, known as the rhizosphere microbiome, consists of a complex array of bacteria, fungi, archaea, [...] Read more.
The rhizosphere, a narrow region of soil surrounding plant roots, is an environment rich in microbial diversity that profoundly influences plants’ health, growth, and agricultural productivity. This microbial community, known as the rhizosphere microbiome, consists of a complex array of bacteria, fungi, archaea, and other microorganisms that engage in complex interactions with plant roots. These microorganisms contribute to nutrient cycling, mineral uptake facilitation, and protection against soil-borne pathogens, thereby promoting plant growth and resilience towards biotic and abiotic stresses. Additionally, microbial signaling molecules, including phytohormones such as auxins, cytokinin, gibberellins, ethylene, and abscisic acid, play a pivotal role in regulating these interactions by modulating plants’ responses to environmental stressors. Recent advancements in microbiomics have enabled a deeper understanding of the rhizosphere’s diversity, composition, and functions, paving the way for more sustainable agricultural practices. By harnessing the potential of the rhizosphere microbiome, innovative strategies can be developed to reduce dependency on synthetic agrochemicals, enhance soil fertility, and increase crop yields. This review discusses the diversity and mechanisms of plant–microbe interactions, focusing on the role of microbial signaling molecules, and explores their applications in promoting agricultural sustainability. The insights gained from microbiomics studies can revolutionize farming practices by reducing dependency on chemical inputs, enhancing crop productivity, and nurturing soil health and environmental sustainability. Full article
(This article belongs to the Special Issue Microbiome in Ecosystem, 3rd Edition)
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