8 results on '"Verónica Sousa"'
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2. Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3.
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Modesto J Remuiñán, Esther Pérez-Herrán, Joaquín Rullás, Carlos Alemparte, María Martínez-Hoyos, David J Dow, Johnson Afari, Nalini Mehta, Jorge Esquivias, Elena Jiménez, Fátima Ortega-Muro, María Teresa Fraile-Gabaldón, Vickey L Spivey, Nicholas J Loman, Mark J Pallen, Chrystala Constantinidou, Douglas J Minick, Mónica Cacho, María José Rebollo-López, Carolina González, Verónica Sousa, Iñigo Angulo-Barturen, Alfonso Mendoza-Losana, David Barros, Gurdyal S Besra, Lluís Ballell, and Nicholas Cammack
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Medicine ,Science - Abstract
Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This 'genetic phenotype' was further confirmed by a 'chemical phenotype', whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice.
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- 2013
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3. Does corporate social responsibility mitigate earnings management?
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Maria Verónica Sousa, Tiago Cruz Gonçalves, and Cristina Gaio
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Management Science and Operations Research ,General Business, Management and Accounting - Abstract
PurposeThis study aims to examine the association between earnings management (EM) and corporate social responsibility (CSR), as well as whether a firm's CSR orientation moderates the trade-off between accruals earnings management (AEM) and real earnings management (REM).Design/methodology/approachFirm-year pooled regressions, based on unbalanced panel data and controlling for country, year and sector fixed effects, were estimated using a sample composed of European companies from 16 countries.FindingsResults suggest a negative relationship between EM and CSR, consistent with the idea that socially responsible activities are associated with more ethical behavior. Moreover, social responsibility orientation seems to mitigate strongly ERM, which may suggest that managers use less REM in order to protect firm's long-term profitability.Practical implicationsThe authors' findings have practical implications for a large group of stakeholders, such as regulators, investors and business partners. Thus, from an ethical perspective, more socially responsible firms present more trustworthy financial information and more sustainable economic performance, which decreases risk assessment from their business partners and remaining stakeholders.Originality/valuePrior literature focuses mainly on discretionary accruals to study the association between EM and CSR. The authors contribute to the literature by considering both EM strategies, accruals and real operations in a European context, which allows for a better understanding of the relationship between CSR and financial information transparency and quality.
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- 2022
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4. Exploring the SAR of the β-Ketoacyl-ACP Synthase Inhibitor GSK3011724A and Optimization around a Genotoxic Metabolite
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Paco de Dios-Anton, Chun-wa Chung, Elena Jimenez, Maria Santos Martinez-Martinez, Fraser Cunningham, Mythily Vimal, Ana Guardia, Raquel Fernandez-Menendez, Arancha Pérez, Jaime Escribano, Jorge Esquivias, Robert H. Bates, María José Rebollo-López, Verónica Sousa-Morcuende, Monica Cacho, Joaquín Rullas, Eva Maria Lopez-Roman, Cristina Rivero, Margaret Neu, and Leticia Huertas Valentín
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0301 basic medicine ,Stereochemistry ,Metabolite ,030106 microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,3-Oxoacyl-(Acyl-Carrier-Protein) Synthase ,Moiety ,Binding site ,chemistry.chemical_classification ,Indazole ,Aniline Compounds ,Binding Sites ,ATP synthase ,biology ,biology.organism_classification ,Anti-Bacterial Agents ,Sulfonamide ,030104 developmental biology ,Infectious Diseases ,chemistry ,biology.protein ,DNA Damage - Abstract
In the course of optimizing a novel indazole sulfonamide series that inhibits β-ketoacyl-ACP synthase (KasA) of Mycobacterium tuberculosis, a mutagenic aniline metabolite was identified. Further lead optimization efforts were therefore dedicated to eliminating this critical liability by removing the embedded aniline moiety or modifying its steric or electronic environment. While the narrow SAR space against the target ultimately rendered this goal unsuccessful, key structural knowledge around the binding site of this underexplored target for TB was generated to inform future discovery efforts.
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- 2020
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5. Stories about transition to higher education: Empirical narrative organization of freshman-year students from south Europe
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C Coelho, Catarina Faria, Verónica Sousa, Nuno Marques, and Luísa Soares
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Higher education ,business.industry ,Transition (fiction) ,Rehabilitation ,language.human_language ,Clinical Psychology ,Stress (linguistics) ,Pedagogy ,medicine ,language ,Narrative ,Sociology ,medicine.symptom ,Portuguese ,business ,Period (music) ,Confusion - Abstract
This study focuses on the transition to higher education experienced by Portuguese freshman-year students, displaced and nondisplaced from their parents homes, residents on a peripheral island located in the south of Europe called Madeira island. To understand better how students perceive this transition, we collected their narratives and analyzed them with three instruments of analysis of narratives: Structure, Process and Content narrative manuals. The results were an indicator of the narrative enrichment of the students in this transition period. The findings indicate that there is no significant differences between the two groups of students in terms of narrative elaboration. The two groups scored low on narrative richness: in terms of content, structure and narrative process. This might be explained by the changes and reorganizations that the transition to higher education system implies, causing stress and confusion on students, that evolve into an impoverishment of their narratives about that trans...
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- 2015
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6. Deambulação entre o crime e o consumo de drogas : uma intervenção juspsicológica
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Marques, Verónica Sousa and Poiares, Carlos Alberto, orient.
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PSYCHOLOGY ,MESTRADO EM PSICOLOGIA FORENSE E EXCLUSÃO SOCIAL ,FORENSIC PSYCHOLOGICAL INTERVENTIONS ,INTERVENÇÃO JUSPSICOLÓGICA ,CONSUMO DE DROGAS ,PSICOLOGIA ,CRIMES ,DRUGS CONSUMPTION - Abstract
Esta dissertação relaciona o consumo da droga e o crime, pois é importante perceber a evolução do fenómeno do consumo, incluindo as substâncias utilizadas e como as próprias substâncias têm vindo a ser alteradas e como a integração das novas drogas afeta a nível físico e psíquico, existindo um desejo ou a necessidade compulsiva de procurar e obter a substância quer pelos seus efeitos, quer para eliminar os sinais de abstinência. A maioria dos consumidores tem patologias associadas como VIH, tuberculose, sífilis entre outros ou psicopatologias, como esquizofrenia. Também a componente criminal em articulação com o uso de drogas deve ser objeto de análise. A segunda parte da dissertação corresponde a um programa de intervenção juspsicológica tendo como objetivo central descrever, analisar e compreender o percurso da passagem da exclusão social como toxicodependente, para uma vida socialmente reinserida. Os objetivos pretendem corresponder às necessidades e caraterísticas específicas da população em causa – toxicodependentes – de forma a promover a inclusão social., This thesis relates to drug use and crime, it is important to recognize how changes in land use and the substances themselves have been changed and as the integration of new drugs affect the physical and mental level and there is a desire or compulsive need to seek and obtain the substance, whether by its effects or to eliminate unpleasant psychic signs that arise with the deprivation of consumption. Most consumers have associated pathologies substances such as VIH, tuberculosis, syphilis among others and psychopathology, as schizophrenia. The concept of crime is also important to be noticed. Then there is talk of Social Reinsertion it is an essential process for anyone who wants to stabilize his life, beginning with the treatment. The second part of Dissertation corresponds to an intervention program with the central objective to describe, analyze and understand the route of the passage of social exclusion as a drug addict for a socially reinserted life. The objectives aim to meet the specific needs and characteristics of the population concerned - drug addicts - in order to promote social inclusion., Orientação: Carlos Alberto Poiares
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- 2016
7. A periodontite como indicador de risco para a peri-implantite
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Martins, Verónica Sousa and Noronha, Susana Canto de
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Doença periodontal ,Implantes endo-ósseos ,Peri-implantite ,Susceptibilidade ,Pacientes periodontalmente comprometidos ,Factor de risco - Abstract
Tese de Mestrado Integrado, Universidade de Lisboa, Faculdade de Medicina Dentária, 2011 Submitted by Maria Luisa Lima Pinheiro (luisa.pinheiro@fmd.ul.pt) on 2012-07-19T10:38:22Z No. of bitstreams: 1 Periodontite como indicador de risco para Peri-implantite.pdf: 954161 bytes, checksum: 624c1012d6e90344cb656d789e756817 (MD5) Made available in DSpace on 2012-07-19T10:46:45Z (GMT). No. of bitstreams: 1 Periodontite como indicador de risco para Peri-implantite.pdf: 954161 bytes, checksum: 624c1012d6e90344cb656d789e756817 (MD5) Previous issue date: 2011
- Published
- 2011
8. Determination of the Pharmacokinetics and Pharmacodynamics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in a Cross-Over Cynomolgus Macaque Model of Mycobacterium tuberculosis Infection
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Laura Sibley, Andrew D. White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro, Laura Alameda, Joaquin Rullas, Veronica Sousa, Marisa Martinez, Inigo Angulo-Barturen, Adolfo Garcia, Juan José Vaquero, Henry E. Pertinez, Geraint Davies, Mike Dennis, Ann Williams, and Sally Sharpe
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tuberculosis ,antibiotics ,pharmacokinetics ,pharmacodynamics ,primates ,Pharmacy and materia medica ,RS1-441 - Abstract
Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of Mycobacterium tuberculosis (M. tb). Although the design accounted for considerable variability between animals, the three regimens evaluated could not be distinguished using any of the alternative endpoints assessed. However, the degree of pathology achieved using H37Rv in the model during this study was less than expected. Based on these findings, a second experiment using a classical AB/BA design comparing HE with HRZ was conducted using the M. tb Erdman strain. More extensive pathology was observed, and differences in computerized tomography (CT) scores and bacteriology counts in the lungs were detected, although due to the small group sizes, clearer differences were not distinguished. Type 1 T helper (Th1) cell response profiles were characterized using the IFN-γ ELISPOT assay and revealed differences between drug treatments that corresponded to decreases in disease burden. Therefore, the studies performed support the utility of the NHP model for the determination of PK/PD of TB drugs, although further work is required to optimize the use of cross-over study designs.
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- 2022
- Full Text
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