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156. O limite do humor no Brasil à luz dos princípios da liberdade de expressão e da dignidade da pessoa humana / The limit of humor in Brazil in the light of the principles of freedom of expression and the dignity of the human person

Author

Luma Vilela Ramos Fonseca and Jean Bazzoni

Subjects
Marketing, Pharmacology, Organizational Behavior and Human Resource Management, Strategy and Management, Drug Discovery, Pharmaceutical Science
Abstract

A presente pesquisa aborda o tema “O Limite do Humor no Brasil à Luz dos Princípios da Liberdade de Expressão e da Dignidade da Pessoa Humana”, que possui grande relevância no cenário atual, ao qual os movimentos humorísticos e o movimento politicamente correto se encontram em alta e, por vezes, entram em rota de colisão, evidenciando a discussão sobre o limite do humor que circunda os princípios da liberdade de expressão e da dignidade da pessoa humana. Portanto, diante desse cenário, a pesquisa tem como objetivo principal analisar a colisão entre os princípios supracitados, a fim de soluciona-la e, como objetivos específicos, analisar o movimento politicamente correto e sua influência no humor, analisar casos envolvendo os princípios da liberdade de expressão e da dignidade da pessoa humana no cenário humorístico e analisar como a liberdade de expressão foi abordada no período ditatorial brasileiro. Sendo assim, por meio da pesquisa bibliográfica e documental realizada, chegou-se à conclusão de que quando os princípios da liberdade de expressão e da dignidade da pessoa humana colidem em temas envolvendo o humor, deve-se aplicar a teoria de sopesamento de Robert Alexy, realizando uma análise de adequação, necessidade e proporcionalidade em sentido estrito e, logo após, aplicar a formula da lei de colisão, qual seja, “(P1 P P2) C à R”, a fim de determinar se o humor praticado ultrapassou o limite da dignidade pessoa humana.

Published
2022
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157. Update on the Role and Utility of Extracellular Vesicles in Hematological Malignancies

Author

Riccardo Bazzoni, Ilaria Tanasi, Nice Turazzi, and Mauro Krampera

Subjects
Extracellular Vesicles, Bone Marrow, Hematologic Neoplasms, Neoplasms, Tumor Microenvironment, Humans, Molecular Medicine, Cell Communication, Cell Biology, Developmental Biology
Abstract

Extracellular vesicles (EVs) are membrane-surrounded cellular particles released by virtually any cell type, containing numerous bioactive molecules, including lipids, proteins, and nucleic acids. EVs act as a very efficient intercellular communication system by releasing their content into target cells, thus affecting their fate and influencing several biological processes. EVs are released both in physiological and pathological conditions, including several types of cancers. In hematological malignancies (HM), EVs have emerged as new critical players, contributing to tumor-to-stroma, stroma-to-tumor, and tumor-to-tumor cell communication. Therefore, EVs have been shown to play a crucial role in the pathogenesis and clinical course of several HM, contributing to tumor development, progression, and drug resistance. Furthermore, tumor EVs can reprogram the bone marrow (BM) microenvironment and turn it into a sanctuary, in which cancer cells suppress both the normal hematopoiesis and the immunological antitumor activity, conferring a therapy-resistant phenotype. Due to their physicochemical characteristics and pro-tumor properties, EVs have been suggested as new diagnostic biomarkers, therapeutic targets, and pharmacological nanocarriers. This review aims to provide an update on the pathogenetic contribution and the putative therapeutic utility of EVs in hematological diseases.

Published
2022
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158. Clinical characteristics, neuroimaging findings, and neuropsychological functioning in attention‐deficit hyperactivity disorder: Sex differences

Author

Sara, Carucci, Chiara, Narducci, Marzia, Bazzoni, Carla, Balia, Federica, Donno, Antonella, Gagliano, and Alessandro, Zuddas

Subjects
Cellular and Molecular Neuroscience
Abstract

Recent clinical studies, in both children/adolescents and adults, have shown the extreme neuropsychological heterogeneity of attention-deficit hyperactivity disorder (ADHD): specific neuropsychological deficits have been found only in a minority of individuals, with no direct correlation between discrete cognitive performances and the trajectory of clinical symptoms. Deficits in specific neuropsychological functions may be common in ADHD, but nevertheless no cognitive or neuropsychological profile may fully explain the disorder. Sex differences in the ADHD presentation, both at a neuropsychological and clinical level, also contribute to this clinical and neuropsychological heterogeneity. At a neuropsychological level, females with ADHD may show greater working memory problems, poorer vocabulary skills and worse visual spatial reasoning. Structural and functional imaging study also show discrete differences across sex; however, the great majority of clinical studies mainly or exclusively include male participants with insufficient data to draw firm conclusions on sex differences within the disorder. Here, we report the recent literature data, discussing still open research questions about the clinical presentation, neuroimaging findings, and neuropsychological functioning in ADHD with a focus on the impact of sex differences-a deeper insight in these unresolved issues may have relevant clinical and therapeutic implications for tailored, effective, and long-lasting interventions.

Published
2022
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164. The Long Non-coding RNA NRIR Drives IFN-Response in Monocytes: Implication for Systemic Sclerosis

Author

Barbara Mariotti, Nila Hendrika Servaas, Marzia Rossato, Nicola Tamassia, Marco A. Cassatella, Marta Cossu, Lorenzo Beretta, Maarten van der Kroef, Timothy R. D. J. Radstake, and Flavia Bazzoni

Subjects
long non-coding RNAs, monocytes, systemic sclerosis, interferon, NRIR, Immunologic diseases. Allergy, RC581-607
Abstract

TLR4 activation initiates a signaling cascade leading to the production of type I IFNs and of the downstream IFN-stimulated genes (ISGs). Recently, a number of IFN-induced long non-coding RNAs (lncRNAs) that feed-back regulate the IFN response have been identified. Dysregulation of this process, collectively known as the “Interferon (IFN) Response,” represents a common molecular basis in the development of autoimmune and autoinflammatory disorders. Concurrently, alteration of lncRNA profile has been described in several type I IFN-driven autoimmune diseases. In particular, both TLR activation and the upregulation of ISGs in peripheral blood mononuclear cells have been identified as possible contributors to the pathogenesis of systemic sclerosis (SSc), a connective tissue disease characterized by vascular abnormalities, immune activation, and fibrosis. However, hitherto, a potential link between specific lncRNA and the presence of a type I IFN signature remains unclear in SSc. In this study, we identified, by RNA sequencing, a group of lncRNAs related to the IFN and anti-viral response consistently modulated in a type I IFN-dependent manner in human monocytes in response to TLR4 activation by LPS. Remarkably, these lncRNAs were concurrently upregulated in a total of 46 SSc patients in different stages of their disease as compared to 18 healthy controls enrolled in this study. Among these lncRNAs, Negative Regulator of the IFN Response (NRIR) was found significantly upregulated in vivo in SSc monocytes, strongly correlating with the IFN score of SSc patients. Weighted Gene Co-expression Network Analysis showed that NRIR-specific modules, identified in the two datasets, were enriched in “type I IFN” and “viral response” biological processes. Protein coding genes common to the two distinct NRIR modules were selected as putative NRIR target genes. Fifteen in silico-predicted NRIR target genes were experimentally validated in NRIR-silenced monocytes. Remarkably, induction of CXCL10 and CXCL11, two IFN-related chemokines associated with SSc pathogenesis, was reduced in NRIR-knockdown monocytes, while their plasmatic level was increased in SSc patients. Collectively, our data show that NRIR affects the expression of ISGs and that dysregulation of NRIR in SSc monocytes may account, at least in part, for the type I IFN signature present in SSc patients.

Published
2019
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165. Production of agrocommodities and consumption of agrochemicals in Uruguay: its repercussions for aquatic systems / Produção de agrocommodities e consumo de agroquímicos no Uruguai: suas repercussões para os sistemas aquáticos

Author

Liliana Terradas-Cobas, Bruno Bazzoni, Carlos Céspedes-Payret, and Daniel Panario

Subjects
General Earth and Planetary Sciences, General Environmental Science
Abstract

The objective of this study is to relate the amount of phosphorus (P) provided by agrochemicals (herbicides and phosphate fertilizers) to soil sown with genetically modified (GM) crops (soybeans and maize) with total phosphorus (TP) in waters of agricultural basins in Uruguay, South America. With this aim, the number of soybean and maize events resistant to glyphosate and glufosinate-ammonium, the total area sown with these GM crops, herbicides and phosphate fertilizers consumption, and TP in the main river of the country in the 2010-2019 period were considered. We found out that the relationship of the annual average of TP with P via herbicides is robust and statically significant, and the relationship with P contribution via fertilizers is strong but no statically significant. Therefore, herbicides must be taken into account as a probable cause of eutrophication of aquatic systems in order to achieve environmental standards.

Published
2022
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166. Impact of Sex on Circulating Leukocytes Composition in COPD Patients

Author

Troianova N, Mariotti B, Micheletti V, Calzetti F, Donini M, Salvagno G, Ferrari M, Crisafulli E, and Bazzoni F

Subjects
Diseases of the respiratory system, blood leukocytes, RC705-779, neutrophil-to-lymphocyte ratio, neutrophilia, sex, copd
Abstract

Natalia Troianova,1,* Barbara Mariotti,1,* Valentina Micheletti,2,3 Federica Calzetti,1 Marta Donini,1 Gianluca Salvagno,4,5 Marcello Ferrari,2,3 Ernesto Crisafulli,2,3 Flavia Bazzoni1 1Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy; 2Department of Medicine, Respiratory Medicine Unit, University of Verona and Verona University Hospital, Verona, Italy; 3Department of Medicine, Section of Internal Medicine, University of Verona and Verona University Hospital, Verona, Italy; 4Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy; 5Service of Laboratory Medicine, Pederzoli Hospital, Peschiera del Garda, Italy*These authors contributed equally to this workCorrespondence: Flavia BazzoniDepartment of Medicine, Division of General Pathology University of Verona, Strada le Grazie 8, Verona, 37134, ItalyTel +39 045 8027128Email flavia.bazzoni@univr.itPurpose: Chronic obstructive pulmonary disease is characterized by chronic inflammatory response both at the lung site and at the systemic level. Abnormalities in circulating leukocytes have been reported to occur in COPD patients and have been often shown to correlate with the decline in lung function. COPD affects men and women at a virtually comparable rate, even though distinct sex specific symptoms, progression and therapeutic implications have been described. Nonetheless, these sex-associated differences have not been analyzed in terms of circulating leukocytes. To assess the impact of sex on the changes of circulating immune cells in COPD patients.Patients and Methods: Blood samples were collected from 50 COPD patients (31 males, 19 females) and 63 age and sex-matched controls (35 males, 28 females) enrolled in this pilot study. Complete blood cell count and multi-parametric flow cytometry analysis were performed to characterize the leukocyte populations and subsets.Results: Male COPD patients are distinguished from controls by a significant increase in white blood cell counts, neutrophil total and differential counts, and neutrophil-to-lymphocyte ratio. Conversely, a generalized leukocyte decrease discriminated female COPD patients from the related controls. The impact of sex is further remarked by a decrease in adaptive immune cell subpopulations in males as opposed to a consistent increase of innate immune cell types in females correlating with disease severity.Conclusion: These data indicate that the definition of specific changes of circulating leukocytes to be used as reliable biomarkers of the disease severity cannot be accomplished irrespectively of sex.Keywords: sex, COPD, blood leukocytes, neutrophil-to-lymphocyte ratio, neutrophilia

Published
2021

171. In‐line multidimensional NMR monitoring of photochemical flow reactions

Author

Margherita Bazzoni, Célia Lhoste, Justine Bonnet, Kouakou Eric Konan, Aurélie Bernard, Patrick Giraudeau, François‐Xavier Felpin, Jean‐Nicolas Dumez, Centre National de la Recherche Scientifique (CNRS), Nantes Université (Nantes Univ), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), ANR-21-CE07-0056,DigitalChem,Synthèse chimique à l'aide d'une plateforme en flux intégrant un algorithm auto-adaptable et une détermination structurale autonome(2021), European Project: 801774,Dinamix, and European Project: 814747,SUMMIT

Subjects
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, [CHIM]Chemical Sciences, General Chemistry, Catalysis
Abstract

International audience; This work demonstrates the in-line monitoring of a flow photochemical reaction using 1D and ultrafast 2D NMR methods at high magnetic field. The reaction mixture exiting the flow reactor is flown trough the NMR spectrometer and directly analysed. In the case of simple substrates, suitable information can be obtained through 1D 1 H spectra, but for molecules of higher complexity the use of 2D experiments is key to address signal overlaps and assignment issues. Here we show the usefulness of ultrafast 2D COSY experiments acquired in 70 s or less, for the in-line monitoring of photochemical reactions, and the possibility to obtain reliable quantitative information. This is a powerful framework to, e.g., efficiently screen reaction conditions.

Published
2023
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174. Il risperidone

Author

Bazzoni, Marzia, primary, Adragna, Carola, additional, and Carucci, Sara, additional

Published
2023
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177. A Year of Bio-Monitoring (2021): Presence of Algae of the Genus Alexandrium, Dinophysis, Prorocentrum and Non-Compliance for Paralytic Toxins and Lipophilic Toxins in Bivalve Mollusks Bred in Sardinia (W Mediterranean Sea)

Author

Lorenzoni, Giuseppa, primary, Bazzoni, Anna Maria, additional, Cangini, Monica, additional, Dall’Ara, Sonia, additional, Melillo, Rita, additional, Mudadu, Alessandro Graziano, additional, Cau, Simona, additional, Soro, Barbara, additional, Ledda, Salvatore, additional, Piras, Gabriella, additional, Tedde, Tiziana, additional, Salza, Sara, additional, Arras, Igor, additional, Porqueddu, Giuseppa, additional, and Meloni, Domenico, additional

Published
2022
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183. Presence, Seasonal Distribution, and Biomolecular Characterization of Vibrio parahaemolyticus and Vibrio vulnificus in Shellfish Harvested and Marketed in Sardinia (Italy) between 2017 and 2018

Author

Igor Arras, Sebastiano Virgilio, Gabriella Piras, Maria Teresa Uda, Giuseppa Lorenzoni, Giuseppe Tedde, T. Tedde, S. Salza, Giuseppe Esposito, Riccardo Bazzardi, Laura Mara, Anna Maria Bazzoni, Domenico Meloni, and Alessandro Graziano Mudadu

Subjects
Mytilus, biology, Vibrio parahaemolyticus, food and beverages, Vibrio vulnificus, biology.organism_classification, Microbiology, Vibrio, Italy, Vibrionaceae, Genotype, Animals, Humans, bacteria, Crassostrea, Seasons, Shellfish, Food Science
Abstract

In the present study, we investigated the presence, seasonal distribution, and biomolecular characteristics of Vibrio parahaemolyticus and Vibrio vulnificus in samples of bivalve mollusks (Mytilus galloprovincialis, Crassostrea gigas, and Ruditapes decussatus) harvested and marketed in Sardinia (Italy) between 2017 and 2018. A total of 435 samples were submitted for qualitative determination of Vibrio spp., V. parahaemolyticus, and V. vulnificus. Potentially enteropathogenic isolates were detected with biomolecular methods. The overall prevalence of Vibrio spp. was 7.6%. The highest Vibrio prevalence was found in R. decussatus (8.3%). The prevalences of V. parahaemolyticus and V. vulnificus were 2.7 and 4.8%, respectively. Higher prevalences of V. parahaemolyticus and V. vulnificus were found in R. decussatus (4.2%) and C. gigas (6.2%), respectively. Only two pathogenic V. parahaemolyticus strains were recovered (genotypes: tdh- and trh+; tdh+ and trh-), both from M. galloprovincialis. None of the isolates were tdh+ and trh+. Pathogenic Vibrio infections are often underestimated, and human infections are increasing in Europe. European data on the true distribution of Vibrionaceae are scarce, and the results of the present study highlight the need of constant monitoring to update the distribution of pathogenic vibrios. HIGHLIGHTS

Published
2021
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184. Yessotoxin detection in bivalve molluscs: A case study from coastal mussel farms (Sardinia, Italy)

Author

Alessandro Graziano Mudadu, Giuseppa Lorenzoni, Anna Maria Bazzoni, Riccardo Bazzardi, Giuseppe Tedde, Igor Arras, Giovanna Sanna, Cinzia Santucciu, Edoardo Marongiu, and Sebastiano Virgilio

Subjects
Lipophilic toxins, Mediterranean, Mussels, Shellfish farms, YTXs, Food processing and manufacture, TP368-456
Abstract

This work reports the first communication relating to the presence of yessotoxins in Mytilus galloprovincialis from coastal mussel farms (Sardinia, western Mediterranean) detected during 2008 and 2013 through a monitoring programme. The paper emphasizes how the changes both in yessotoxin permitted limits and used methods, established by legislation, have influenced the interpretation of the obtained results. Consequently, the samples that resulted negative during 2008 would have been positive until August 2013 and negative from September 2013 up to now, and the samples that were positive in 2013 would have been positive in 2008 and negative nowadays, according to Regulation currently in force. Regular monitoring of biotoxins demonstrated that, although yessotoxins have been rarely present in the past in Sardinia, they may cause toxicity in shellfish. So, it’s important to keep up on legislation’s changing and laboratory methods.

Published
2018
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185. Comment on: "Back to the future? Conservative grassland management can preserve soil health in the changing landscapes of Uruguay" On the risks of good intentions and poor evidence.

Author

Paruelo, José, Lopez-Marsico, Luis, Baldassini, Pablo, Lezama, Felipe, Bazzoni, Bruno, Staiano, Luciana, Nuñez, Agustín, Guido, Anaclara, Ríos, Cecilia, Tommasino, Andrea, Gallego, Federico, Pezzani, Fabiana, Sans, Gonzalo Camba, Quincke, Andrés, Baeza, Santiago, Piñeiro, Gervasio, and Baethgen, Walter

Subjects
LANDSCAPE changes, GRASSLANDS, DEVELOPING countries, SOILS, PLATEAUS, DEVELOPED countries
Abstract

In this article we make comments on some methodological issues and on the general approach of the paper "Back to the future? Conservative grassland management can preserve soil health in the changing landscapes of Uruguay" by Ina Säumel, Leonardo R. Ramírez, Sarah Tietjen, Marcos Barra, and Erick Zagal, Soil 9, 425–442, https://doi.org/10.5194/soil-9-425-2023. We identified various design and methodological problems that may induce potential misinterpretations. Our concerns are of three different types. First, there are aspects of the study design and methodology that, in our opinion, introduce biases and critical errors. Secondly, the article does not put forth any novel propositions and ignores extensive local literature and aspects that are central to the interpretation of the data Finally, we are concerned about the possible interpretations of a study, generated from institutions based on developed countries with not the participation of local scientists from the Global South in the design of policies and development of non-tariff barriers for South American countries. [ABSTRACT FROM AUTHOR]

Published
2023
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186. Translating across Lines of Identity and Domination: The Case of M. NourbeSe Philip's Zong!

Author

Bazzoni, Alberica

Subjects
POSTCOLONIAL literature, SEXISM, PARADIGM (Linguistics), COLONIAL animals (Marine invertebrates), AUTHORSHIP
Abstract

This article examines the case of the recent 'unauthorised' translation of Caribbean-Canadian poet M. NourbeSe Philip's Zong! (2008) into Italian, which was at the centre of a heated debate on authorship and coloniality. The author unravels the rhetoric used in clashing arguments and identifies underlying values and assumptions to expose the system of power and the historical context in which this confrontation took place. Through an investigation of questions of authorship, authority and ethical posture, the author draws a distinction between a legalistic and a relational paradigm of translation. The article foregrounds the critical role of identity in the translation process and uncovers the enduring of colonial, racist and sexist structures embedded in the international publishing world, exposing both the limits and the creative potential of translation as a cultural practice that is deeply political. [ABSTRACT FROM AUTHOR]

Published
2023
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189. Prüfer rings

Author

Bazzoni, Silvana, Glaz, Sarah, Brewer, James W., editor, Glaz, Sarah, editor, Heinzer, William J., editor, and Olberding, Bruce M., editor

Published
2006
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190. Correction: Occurrence of harmful algal species and shellfish toxicity in Sardinia (Italy)

Author

Anna Maria Bazzoni, Alessandro Graziano Mudadu, Giuseppa Lorenzoni, Igor Arras, Antonella Lugliè, Barbara Vivaldi, Valentina Ciccotelli, Giovanna Sanna, Giuseppe Tedde, Salvatore Ledda, Enrico Alesso, Edoardo Marongiu, and Sebastiano Virgilio

Subjects
Biotoxins, Potentially toxic microalgae, Shellfish farms, Mediterranean, Food processing and manufacture, TP368-456
Abstract

Not available.

Published
2017
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191. Reduction in Time:Kinaesthetic and Traumatic Experiences of the Present in Literary Texts

Author

Alberica Bazzoni

Subjects
Epochē, Affect, Becoming (Philosophy), Temporality, Literature, Living present, Trauma
Abstract

The chapter explores the dimension of the living present as a form of temporal reduction, looking at its manifestation in literary texts. Bazzoni proposes here a focus on the living present as different from a still, eternal moment, and contrasts the experience of the living present with the reduction at play in trauma. Finally, the author discusses the affective, ethical, and political dimensions of the temporality of the living present as a site of subjectivation, which effects a counter-reduction of normative discourses. Alberica Bazzoni, ‘Reduction in Time: Kinaesthetic and Traumatic Experiences of the Present in Literary Texts’, in The Case for Reduction, ed. by Christoph F. E. Holzhey and Jakob Schillinger, Cultural Inquiry, 25 (Berlin: ICI Berlin Press, 2022), pp. 191-212

Published
2022

192. Substrate stiffness reduces particle uptake by epithelial cells and macrophages in a size-dependent manner through mechanoregulation

Author

Aaron Lee, Mauro Sousa de Almeida, Daela Milinkovic, Dedy Septiadi, Patricia Taladriz-Blanco, Céline Loussert-Fonta, Sandor Balog, Amelie Bazzoni, Barbara Rothen-Rutishauser, and Alke Petri-Fink

Subjects
stiffness, topography, Macrophages, Cell Adhesion, endocytosis, Polystyrenes, General Materials Science, YAP-Signaling Proteins, Epithelial Cells, Dimethylpolysiloxanes, mechanobiology, particle uptake, Mechanotransduction, Cellular
Abstract

Cells continuously exert forces on their environment and respond to changes in mechanical forces by altering their behaviour. Many pathologies such as cancer and fibrosis are hallmarked by dysregulation in the extracellular matrix, driving aberrant behaviour through mechanotransduction pathways. We demonstrate that substrate stiffness can be used to regulate cellular endocytosis of particles in a size-dependent fashion. Culture of A549 epithelial cells and J774A.1 macrophages on polystyrene/glass (stiff) and polydimethylsiloxane (soft) substrates indicated that particle uptake is increased up to six times for A549 and two times for macrophages when cells are grown in softer environments. Furthermore, we altered surface characteristics through the attachment of submicron-sized particles as a method to locally engineer substrate stiffness and topography to investigate the biomechanical changes which occurred within adherent epithelial cells,i.e.characterization of A549 cell spreading and focal adhesion maturation. Consequently, decreasing substrate rigidity and particle-based topography led to a reduction of focal adhesion size. Moreover, expression levels of Yes-associated protein were found to correlate with the degree of particle endocytosis. A thorough appreciation of the mechanical cues may lead to improved solutions to optimize nanomedicine approaches for treatment of cancer and other diseases with abnormal mechanosignalling.

Published
2022

194. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author

Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B Scirica, S Shah, C Wanner, D Aizenberg, L Cartasegna, F Colombo Berra, H Colombo, M Fernandez Moutin, J Glenny, C Alvarez Lorio, D Anauch, R Campos, A Facta, A Fernandez, R Ahuad Guerrero, L Lobo Márquez, RA Leon de la Fuente, M Mansilla, M Hominal, E Hasbani, M Najenson, G Moises Azize, H Luquez, L Guzman, H Sessa, M Amuchástegui, O Salomone, E Perna, D Piskorz, M Sicer, D Perez de Arenaza, C Zaidman, S Nani, C Poy, J Resk, R Villarreal, C Majul, T Smith Casabella, S Sassone, A Liberman, G Carnero, A Caccavo, M Berli, N Budassi, J Bono, A Alvarisqueta, J Amerena, K Kostner, A Hamilton, A Begg, J Beltrame, D Colquhoun, G Gordon, A Sverdlov, G Vaddadi, J Wong, J Coller, D Prior, A Friart, A Leone, G Vervoort, P Timmermans, P Troisfontaines, C Franssen, T Sarens, H Vandekerckhove, P Van De Borne, F Chenot, J De Sutter, E De Vuyst, P Debonnaire, M Dupont, O Pereira Dutra, LH Canani, MdC Vieira Moreira, W de Souza, LM Backes, L Maia, B De Souza Paolino, ER Manenti, W Saporito, F Villaça Guimarães Filho, T Franco Hirakawa, LA Saliba, FC Neuenschwander, CA de Freitas Zerbini, G Gonçalves, Y Gonçalves Mello, J Ascenção de Souza, L Beck da Silva Neto, EA Bocchi, J Da Silveira, JB de Moura Xavier Moraes Junior, JD de Souza Neto, M Hernandes, HC Finimundi, CR Sampaio, E Vasconcellos, FJ Neves Mancuso, MM Noya Rabelo, M Rodrigues Bacci, F Santos, M Vidotti, MV Simões, FL Gomes, C Vieira Nascimento, D Precoma, FA Helfenstein Fonseca, JA Ribas Fortes, PE Leães, D Campos de Albuquerque, JF Kerr Saraiva, S Rassi, FA Alves da Costa, G Reis, S Zieroth, D Dion, D Savard, R Bourgeois, C Constance, K Anderson, M-H Leblanc, D Yung, E Swiggum, L Pliamm, Y Pesant, B Tyrrell, T Huynh, J Spiegelman, J-P Lavoie, M Hartleib, R Bhargava, L Straatman, S Virani, A Costa-Vitali, L Hill, M Heffernan, Y Khaykin, J Ricci, M Senaratne, A Zhai, B Lubelsky, M Toma, L Yao, R McKelvie, L Noronha, M Babapulle, A Pandey, G Curnew, A Lavoie, J Berlingieri, S Kouz, E Lonn, R Chehayeb, Y Zheng, Y Sun, H Cui, Z Fan, X Han, X Jiang, Q Tang, J Zhou, Z Zheng, X Zhang, N Zhang, Y Zhang, A Shen, J Yu, J Ye, Y Yao, J Yan, X Xu, Z Wang, J Ma, Y Li, S Li, S Lu, X Kong, Y Song, G Yang, Z Yao, Y Pan, X Guo, Z Sun, Y Dong, J Zhu, D Peng, Z Yuan, J Lin, Y Yin, O Jerabek, H Burianova, T Fiala, J Hubac, O Ludka, Z Monhart, P Vodnansky, K Zeman, D Foldyna, J Krupicka, I Podpera, L Busak, M Radvan, Z Vomacka, R Prosecky, R Cifkova, V Durdil, J Vesely, J Vaclavik, P Cervinka, A Linhart, T Brabec, R Miklik, H Bourhaial, H-G Olbrich, S Genth-Zotz, E Kemala, B Lemke, M Böhm, S Schellong, W Rieker, T Heitzer, H Ince, M Faghih, A Birkenfeld, A Begemann, A Ghanem, A Ujeyl, S von Haehling, T Dorsel, J Bauersachs, M Prull, F Weidemann, H Darius, G Nickenig, A Wilke, J Sauter, U Rauch-Kroehnert, N Frey, CP Schulze, W König, L Maier, F Menzel, N Proskynitopoulos, H-H Ebert, H-E Sarnighausen, H-D Düngen, M Licka, C Stellbrink, B Winkelmann, N Menck, JL López-Sendón, L de la Fuente Galán, JF Delgado Jiménez, N 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Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, medicine.medical_specialty, Angiotensin receptor, Glucoside, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, Glucosides, Double-Blind Method, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, ComputingMilieux_MISCELLANEOUS, Aged, Benzhydryl Compound, Heart Failure, Ejection fraction, business.industry, Angiotensin Receptor Antagonist, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Stroke Volume, medicine.disease, 3. Good health, Heart failure, ACE inhibitor, Female, Hypotension, business, medicine.drug, Human
Abstract

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

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2022
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195. Gut Microbiome-Derived Metabolite Trimethylamine N-Oxide Induces Aortic Stiffening and Increases Systolic Blood Pressure With Aging in Mice and Humans

Author

Amy E Bazzoni, Andrew P. Neilson, Abigail G. Casso, Vienna E. Brunt, Melanie C. Zigler, Douglas R. Seals, David A. Hutton, James J Richey, Zachary J Sapinsley, Zachary S. Clayton, Kevin P. Davy, Brian P. Ziemba, Nicholas S. VanDongen, and Rachel A. Gioscia-Ryan

Subjects
0301 basic medicine, medicine.medical_specialty, Aorta, Chemistry, Trimethylamine N-oxide, 030204 cardiovascular system & hematology, medicine.disease, Alagebrium, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Blood pressure, Endocrinology, Glycation, Internal medicine, medicine.artery, cardiovascular system, Internal Medicine, medicine, Arterial stiffness, Aortic stiffness, Pulse wave velocity, medicine.drug
Abstract

Aging is associated with stiffening of the large elastic arteries and consequent increases in systolic blood pressure (SBP), which together increase cardiovascular disease risk; however, the upstream mechanisms are incompletely understood. Using complementary translational approaches in mice and humans, we investigated the role of the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO) in age-related aortic stiffening and increased SBP. Aortic stiffness was measured using carotid-femoral or aortic pulse wave velocity (PWV) in humans and mice, respectively. Study 1: Plasma TMAO concentrations were elevated ( P r 2 =0.15, P r 2 =0.09, P

Published
2021
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196. IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study

Author

Roberto Latini, Gian F Mureddu, Predictor Investigators, Luisa Ojeda-Fernandez, Lidia Staszewsky, Deborah Novelli, Peter Kastner, Serge Masson, Maurizio Mangiavacchi, Jennifer Meessen, Ursula-Henrike Wienhues-Thelen, Gianfranco Bazzoni, Giulia Cesaroni, Nera Agabiti, and Alessandro Boccanelli

Subjects
Male, Time Factors, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, Ventricular Dysfunction, Left, 0302 clinical medicine, Risk Factors, Cause of Death, Prevalence, Registries, Aged, 80 and over, education.field_of_study, Hazard ratio, Age Factors, Atrial fibrillation, Prognosis, Cardiac surgery, Insulin-Like Growth Factor Binding Proteins, Italy, Cohort, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Procollagen, Research Article, medicine.medical_specialty, Growth Differentiation Factor 15, Population, 030209 endocrinology & metabolism, Asymptomatic, Risk Assessment, 03 medical and health sciences, Internal medicine, medicine, Cardiac remodelling, Humans, Diseases of the circulatory (Cardiovascular) system, P1NP, education, Community-dwelling elderly, Angiology, Aged, Heart Failure, business.industry, medicine.disease, Peptide Fragments, GDF-15, Cross-Sectional Studies, RC666-701, IGFBP7, business, Biomarkers
Abstract

BackgroundLittle is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study.Methods2001 community-dwelling subjects aged 65–84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e’ (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years.ResultsIGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08–4.22] and 2.03[1.62–2.56] per unit increase of Ln-transformed markers, respectively.ConclusionsIn a community-based elderly cohort,IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Published
2021

197. Notch signaling and MicroRNA: The dynamic duo steering between neurogenesis and glioblastomas

Author

Javed, Z, Khan, K, Raza, Q, Sadia, H, Shah, F, Ahmad, T, Bentivegna, A, Bazzoni, R, Setzer, W, Alshehri, M, Dastan, S, Sharifi-Rad, J, Javed Z., Khan K., Raza Q., Sadia H., Shah F. A., Ahmad T., Bentivegna A., Bazzoni R., Setzer W. N., Alshehri M. M., Dastan S. D., Sharifi-Rad J., Javed, Z, Khan, K, Raza, Q, Sadia, H, Shah, F, Ahmad, T, Bentivegna, A, Bazzoni, R, Setzer, W, Alshehri, M, Dastan, S, Sharifi-Rad, J, Javed Z., Khan K., Raza Q., Sadia H., Shah F. A., Ahmad T., Bentivegna A., Bazzoni R., Setzer W. N., Alshehri M. M., Dastan S. D., and Sharifi-Rad J.

Abstract

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates processes of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are orchestrated by Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive roles in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in the development of the nervous system and how this versatile pathway interplays with microRNAs in glioblastoma. This review sheds light on the interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs-mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

Published
2021

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