Publications by authors named "Carla Sousa"

158 Publications

Dissection of anterior mitral valve leaflet masking severe mitral regurgitation - an unusual case of infective endocarditis.

Acta Cardiol 2021 Jul 13:1-3. Epub 2021 Jul 13.

Serviço de Cardiologia, Centro Hospitalar Universitário de São João, Porto, Portugal.

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http://dx.doi.org/10.1080/00015385.2021.1950370DOI Listing
July 2021

Wide and increasing suitability for Aedes albopictus in Europe is congruent across distribution models.

Sci Rep 2021 May 10;11(1):9916. Epub 2021 May 10.

Centre for Geographical Studies, Institute of Geography and Spatial Planning, Universidade de Lisboa, Lisbon, Portugal.

The Asian tiger mosquito (Aedes albopictus), a vector of dengue, Zika and other diseases, was introduced in Europe in the 1970s, where it is still widening its range. Spurred by public health concerns, several studies have delivered predictions of the current and future distribution of the species for this region, often with differing results. We provide the first joint analysis of these predictions, to identify consensus hotspots of high and low suitability, as well as areas with high uncertainty. The analysis focused on current and future climate conditions and was carried out for the whole of Europe and for 65 major urban areas. High consensus on current suitability was found for the northwest of the Iberian Peninsula, southern France, Italy and the coastline between the western Balkans and Greece. Most models also agree on a substantial future expansion of suitable areas into northern and eastern Europe. About 83% of urban areas are expected to become suitable in the future, in contrast with ~ 49% nowadays. Our findings show that previous research is congruent in identifying wide suitable areas for Aedes albopictus across Europe and in the need to effectively account for climate change in managing and preventing its future spread.
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http://dx.doi.org/10.1038/s41598-021-89096-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110805PMC
May 2021

A Case for Systematic Quality Management in Mosquito Control Programmes in Europe.

Int J Environ Res Public Health 2021 03 27;18(7). Epub 2021 Mar 27.

Laboratory of Entomology and Agricultural Zoology, University of Thessaly, 38446 Volos, Greece.

The recent spread of invasive mosquito species, such as and the seasonal sporadic transmission of autochthonous cases of arboviral diseases (e.g., dengue, chikungunya, Zika) in temperate areas, such as Europe and North America, highlight the importance of effective mosquito-control interventions to reduce not only nuisance, but also major threats for public health. Local, regional, and even national mosquito control programs have been established in many countries and are executed on a seasonal basis by either public or private bodies. In order for these interventions to be worthwhile, funding authorities should ensure that mosquito control is (a) planned by competent scientific institutions addressing the local demands, (b) executed following the plan that is based on recommended and effective methods and strategies, (c) monitored regularly by checking the efficacy of the implemented actions, (d) evaluated against the set of targets, and (e) regularly improved according to the results of the monitoring. Adherence to these conditions can only be assured if a formal quality management system is adopted and enforced that ensures the transparency of effectiveness of the control operation. The current paper aims at defining the two components of this quality management system, quality assurance and quality control for mosquito control programs with special emphasis on Europe, but applicable over temperate areas.
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http://dx.doi.org/10.3390/ijerph18073478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037277PMC
March 2021

Passive Diffusion of Ciprofloxacin and its Metalloantibiotic: A Computational and Experimental study.

J Mol Biol 2021 04 4;433(9):166911. Epub 2021 Mar 4.

LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. Electronic address:

Fluoroquinolones (FQ) are antibiotics widely used in clinical practise, but the development of bacterial resistance to these drugs is currently a critical public health problem. In this context, ternary copper complexes of FQ (CuFQPhen) have been studied as a potential alternative. In this study, we compared the passive diffusion across the lipid bilayer of one of the most used FQ, ciprofloxacin (Cpx), and its ternary copper complex, CuCpxPhen, that has shown previous promising results regarding antibacterial activity and membrane partition. A combination of spectroscopic studies and molecular dynamics simulations were used and two different model membranes tested: one composed of anionic phospholipids, and the other composed of zwitterionic phospholipids. The obtained results showed a significantly higher membrane permeabilization activity, larger partition, and a more favourable free energy landscape for the permeation of CuCpxPhen across the membrane, when compared to Cpx. Furthermore, the computational results indicated a more favourable translocation of CuCpxPhen across the anionic membrane, when compared to the zwitterionic one, suggesting a higher specificity towards the former. These findings are important to decipher the influx mechanism of CuFQPhen in bacterial cells, which is crucial for the ultimate use of CuFQPhen complexes as an alternative to FQ to tackle multidrug-resistant bacteria.
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http://dx.doi.org/10.1016/j.jmb.2021.166911DOI Listing
April 2021

C-Glucosylation as a tool for the prevention of PAINS-induced membrane dipole potential alterations.

Sci Rep 2021 Feb 24;11(1):4443. Epub 2021 Feb 24.

Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016, Lisboa, Portugal.

The concept of Pan-Assay Interference Compounds (PAINS) is regarded as a threat to the recognition of the broad bioactivity of natural products. Based on the established relationship between altered membrane dipole potential and transmembrane protein conformation and function, we investigate here polyphenols' ability to induce changes in cell membrane dipole potential. Ultimately, we are interested in finding a tool to prevent polyphenol PAINS-type behavior and produce compounds less prone to untargeted and promiscuous interactions with the cell membrane. Di-8-ANEPPS fluorescence ratiometric measurements suggest that planar lipophilic polyphenols-phloretin, genistein and resveratrol-act by decreasing membrane dipole potential, especially in cholesterol-rich domains such as lipid rafts, which play a role in important cellular processes. These results provide a mechanism for their labelling as PAINS through their ability to disrupt cell membrane homeostasis. Aiming to explore the role of C-glucosylation in PAINS membrane-interfering behavior, we disclose herein the first synthesis of 4-glucosylresveratrol, starting from 5-hydroxymethylbenzene-1,3-diol, via C-glucosylation, oxidation and Horner-Wadsworth-Emmons olefination, and resynthesize phloretin and genistein C-glucosides. We show that C-glucosylation generates compounds which are no longer able to modify membrane dipole potential. Therefore, it can be devised as a strategy to generate bioactive natural product derivatives that no longer act as membrane dipole potential modifiers. Our results offer a new technology towards rescuing bioactive polyphenols from their PAINS danger label through C-C ligation of sugars.
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http://dx.doi.org/10.1038/s41598-021-83032-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904931PMC
February 2021

How Insertion of a Single Tryptophan in the N-Terminus of a Cecropin A-Melittin Hybrid Peptide Changes Its Antimicrobial and Biophysical Profile.

Membranes (Basel) 2021 Jan 12;11(1). Epub 2021 Jan 12.

Laboratório Associado para a Química Verde da Rede de Química e Tecnologia (LAQV-REQUIMTE), Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal.

In the era of antibiotic resistance, there is an urgent need for efficient antibiotic therapies to fight bacterial infections. Cationic antimicrobial peptides (CAMP) are promising lead compounds given their membrane-targeted mechanism of action, and high affinity towards the anionic composition of bacterial membranes. We present a new CAMP, W-BP100, derived from the highly active BP100, holding an additional tryptophan at the N-terminus. W-BP100 showed a broader antibacterial activity, demonstrating a potent activity against Gram-positive strains. Revealing a high partition constant towards anionic over zwitterionic large unilamellar vesicles and inducing membrane saturation at a high peptide/lipid ratio, W-BP100 has a preferential location for hydrophobic environments. Contrary to BP100, almost no aggregation of anionic vesicles is observed around saturation conditions and at higher concentrations no aggregation is observed. With these results, it is possible to state that with the incorporation of a single tryptophan to the N-terminus, a highly active peptide was obtained due to the π-electron system of tryptophan, resulting in negatively charged clouds, that participate in cation-π interactions with lysine residues. Furthermore, we propose that W-BP100 action can be achieved by electrostatic interactions followed by peptide translocation.
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http://dx.doi.org/10.3390/membranes11010048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826622PMC
January 2021

Fluoroquinolone Metalloantibiotics to Bypass Antimicrobial Resistance Mechanisms: Decreased Permeation through Porins.

Membranes (Basel) 2020 Dec 22;11(1). Epub 2020 Dec 22.

REQUIMTE-LAQV (Rede de Química e Tecnologia-Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica, da Faculdade de Ciências, da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal.

Fluoroquinolones (FQs) are broad-spectrum antibiotics largely used in the clinical practice against Gram-negative and some Gram-positive bacteria. Nevertheless, bacteria have developed several antimicrobial resistance mechanisms against such class of antibiotics. Ternary complexes of FQs, copper(II) and phenanthroline, known as metalloantibiotics, arise in an attempt to counteract an antibiotic resistance mechanism related to low membrane permeability. These metalloantibiotics seem to use an alternative influx route, independent of porins. The translocation pathways of five FQs and its metalloantibiotics were studied through biophysical experiments, allowing us to infer about the role of OmpF porin in the influx. The FQ-OmpF interaction was assessed in mimetic membrane systems differing on the lipidic composition, disclosing no interference of the lipidic composition. The drug-porin interaction revealed similar values for the association constants of FQs and metalloantibiotics with native OmpF. Therefore, OmpF mutants and specific quenchers were used to study the location-association relationship, comparing a free FQ and its metalloantibiotic. The free FQ revealed a specific association, with preference for residues on the centre of OmpF, while the metalloantibiotic showed a random interaction. Thereby, metalloantibiotics may be an alternative to pure FQs, being able to overcome some antimicrobial resistance mechanism of Gram-negative bacteria related to decreased membrane permeability.
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http://dx.doi.org/10.3390/membranes11010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822003PMC
December 2020

Left ventricular pacing with a temporary pacemaker: Case report.

Rev Port Cardiol (Engl Ed) 2021 Feb 26;40(2):141.e1-141.e4. Epub 2020 Dec 26.

Department of Cardiology, Centro Hospitalar São João, EPE, Porto, Portugal.

We report a case of temporary pacemaker lead malposition in the left ventricle crossing the interventricular septum (IVS). The majority of described cases occur due to a patent foramen ovale and are frequently incidental findings. A course across the IVS is rarely found and this complication with temporary leads is not even reported in the literature. This very rare location entails a risk of dangerous complications associated with left-to-right flow after lead removal. Echocardiography was an essential tool to diagnose the lead's course inside the heart and enabled secure removal of the lead with cardiac surgery backup.
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http://dx.doi.org/10.1016/j.repc.2020.12.006DOI Listing
February 2021

Pacman heart: An unexpected finding.

Rev Port Cardiol (Engl Ed) 2020 Nov 2;39(11):674-675. Epub 2020 Nov 2.

Serviço de Cardiologia, Centro Hospitalar Universitário de São João, Porto, Portugal.

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http://dx.doi.org/10.1016/j.repc.2019.10.010DOI Listing
November 2020

[Thoughts about the Impact Factor].

Acta Med Port 2020 Oct 1;33(10):633-634. Epub 2020 Oct 1.

Acta Médica Portuguesa. Ordem dos Médicos. Lisboa. Portugal.

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http://dx.doi.org/10.20344/amp.14773DOI Listing
October 2020

Simulation models of dengue transmission in Funchal, Madeira Island: Influence of seasonality.

PLoS Negl Trop Dis 2020 10 5;14(10):e0008679. Epub 2020 Oct 5.

Florida Medical Entomology Laboratory, Institute of Food and Agricultural Sciences, University of Florida, Vero Beach, Florida, United States of America.

The recent emergence and established presence of Aedes aegypti in the Autonomous Region of Madeira, Portugal, was responsible for the first autochthonous outbreak of dengue in Europe. The island has not reported any dengue cases since the outbreak in 2012. However, there is a high risk that an introduction of the virus would result in another autochthonous outbreak given the presence of the vector and permissive environmental conditions. Understanding the dynamics of a potential epidemic is critical for targeted local control strategies. Here, we adopt a deterministic model for the transmission of dengue in Aedes aegypti mosquitoes. The model integrates empirical and mechanistic parameters for virus transmission, under seasonally varying temperatures for Funchal, Madeira Island. We examine the epidemic dynamics as triggered by the arrival date of an infectious individual; the influence of seasonal temperature mean and variation on the epidemic dynamics; and performed a sensitivity analysis on the following quantities of interest: the epidemic peak size, time to peak, and the final epidemic size. Our results demonstrate the potential for summer and autumn season transmission of dengue, with the arrival date significantly affecting the distribution of the timing and peak size of the epidemic. Late-summer arrivals were more likely to produce large epidemics within a short peak time. Epidemics within this favorable period had an average of 11% of the susceptible population infected at the peak, at an average peak time of 95 days. We also demonstrated that seasonal temperature variation dramatically affects the epidemic dynamics, with warmer starting temperatures producing large epidemics with a short peak time and vice versa. Overall, our quantities of interest were most sensitive to variance in the date of arrival, seasonal temperature, transmission rates, mortality rate, and the mosquito population; the magnitude of sensitivity differs across quantities. Our model could serve as a useful guide in the development of effective local control and mitigation strategies for dengue fever in Madeira Island.
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http://dx.doi.org/10.1371/journal.pntd.0008679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561266PMC
October 2020

A Case of Acute Myocardial Infarction and Pericarditis Unmasking Metastatic Involvement of the Heart.

Arq Bras Cardiol 2020 04;115(1 suppl 1):22-24

Centro Hospitalar Universitário de São João, Porto - Portugal.

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http://dx.doi.org/10.36660/abc.20190534DOI Listing
April 2020

Biophysical Analysis of Lipid Domains in Mammalian and Yeast Membranes by Fluorescence Spectroscopy.

Methods Mol Biol 2021 ;2187:247-269

Centro de Química e Bioquímica, Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.

The use of steady-state and time-resolved fluorescence spectroscopy to study sterol and sphingolipid-enriched lipid domains as diverse as the ones found in mammalian and fungal membranes is herein described. We first address how to prepare liposomes that mimic raft-containing membranes of mammalian cells and how to use fluorescence spectroscopy to characterize the biophysical properties of these membrane model systems. We further illustrate the application of Förster resonance energy transfer (FRET) to study nanodomain reorganization upon interaction with small bioactive molecules, phenolic acids, an important group of phytochemical compounds. This methodology overcomes the resolution limits of conventional fluorescence microscopy allowing for the identification and characterization of lipid domains at the nanoscale.We continue by showing how to use fluorescence spectroscopy in the biophysical analysis of more complex biological systems, namely the plasma membrane of Saccharomyces cerevisiae yeast cells and the necessary adaptations to the filamentous fungus Neurospora crassa , evaluating the global order of the membrane, sphingolipid-enriched domains rigidity and abundance, and ergosterol-dependent properties.
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http://dx.doi.org/10.1007/978-1-0716-0814-2_14DOI Listing
March 2021

Predicting dengue importation into Europe, using machine learning and model-agnostic methods.

Sci Rep 2020 06 16;10(1):9689. Epub 2020 Jun 16.

Centro de Estudos Geográficos, Instituto de Geografia e Ordenamento do Território - IGOT, Universidade de Lisboa, 1600-276, Lisboa, Portugal.

The geographical spread of dengue is a global public health concern. This is largely mediated by the importation of dengue from endemic to non-endemic areas via the increasing connectivity of the global air transport network. The dynamic nature and intrinsic heterogeneity of the air transport network make it challenging to predict dengue importation. Here, we explore the capabilities of state-of-the-art machine learning algorithms to predict dengue importation. We trained four machine learning classifiers algorithms, using a 6-year historical dengue importation data for 21 countries in Europe and connectivity indices mediating importation and air transport network centrality measures. Predictive performance for the classifiers was evaluated using the area under the receiving operating characteristic curve, sensitivity, and specificity measures. Finally, we applied practical model-agnostic methods, to provide an in-depth explanation of our optimal model's predictions on a global and local scale. Our best performing model achieved high predictive accuracy, with an area under the receiver operating characteristic score of 0.94 and a maximized sensitivity score of 0.88. The predictor variables identified as most important were the source country's dengue incidence rate, population size, and volume of air passengers. Network centrality measures, describing the positioning of European countries within the air travel network, were also influential to the predictions. We demonstrated the high predictive performance of a machine learning model in predicting dengue importation and the utility of the model-agnostic methods to offer a comprehensive understanding of the reasons behind the predictions. Similar approaches can be utilized in the development of an operational early warning surveillance system for dengue importation.
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http://dx.doi.org/10.1038/s41598-020-66650-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298036PMC
June 2020

Caseous calcification of the mitral annulus in a cardiac arrest survivor.

Rev Port Cardiol (Engl Ed) 2020 May 10;39(5):295-297. Epub 2020 Jun 10.

Serviço de Cardiologia, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

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http://dx.doi.org/10.1016/j.repc.2019.09.012DOI Listing
May 2020

[How Acta Médica Portuguesa Adjusted to Pandemic Times].

Acta Med Port 2020 06 31;33(6):357-358. Epub 2020 May 31.

Acta Médica Portuguesa. Ordem dos Médicos. Lisboa. Portugal.

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http://dx.doi.org/10.20344/amp.14080DOI Listing
June 2020

Echocardiographic appearance of a rare condition - tracheobronchomegaly.

Rev Port Cardiol (Engl Ed) 2020 Apr 20;39(4):229-230. Epub 2020 May 20.

Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal.

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http://dx.doi.org/10.1016/j.repc.2019.03.010DOI Listing
April 2020

The V410L knockdown resistance mutation occurs in island and continental populations of Aedes aegypti in West and Central Africa.

PLoS Negl Trop Dis 2020 05 8;14(5):e0008216. Epub 2020 May 8.

Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisbon, Portugal.

The extensive use of insecticides for vector control has led to the development of insecticide resistance in Aedes aegypti populations on a global scale, which has significantly compromised control actions. Insecticide resistance, and its underlying mechanisms, has been investigated in several countries, mostly in South American and Asian countries. In Africa, however, studies reporting insecticide resistance are rare and data on resistance mechanisms, notably knockdown resistance (kdr) mutations, is scarce. In this study, the recently described V410L kdr mutation is reported for the first time in old world Ae. aegypti populations, namely from Angola and Madeira island. Two additional kdr mutations, V1016I and F1534C, are also reported for the first time in populations from Angola and Cape Verde. Significant associations with the resistance phenotype were found for both V410L and V1016I individually as well as for tri-locus genotypes in the Angolan population. However, no association was found in Madeira island, probably due to the presence of a complex pattern of multiple insecticide resistance mechanisms in the local Ae. aegypti population. These results suggest that populations carrying the same kdr mutations may respond differently to the same insecticide, stressing the need for complementary studies when assessing the impact of kdr resistance mechanisms in the outcome of insecticide-based control strategies.
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http://dx.doi.org/10.1371/journal.pntd.0008216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304628PMC
May 2020

Fluoroquinolone Metalloantibiotics: A Promising Approach against Methicillin-Resistant .

Int J Environ Res Public Health 2020 04 30;17(9). Epub 2020 Apr 30.

REQUIMTE-LAQV (Rede de Química e Tecnologia - Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal.

Fluoroquinolones (FQs) are antibiotics commonly used in clinical practice, although nowadays they are becoming ineffective due to the emergence of several mechanisms of resistance in most bacteria. The complexation of FQs with divalent metal ions and phenanthroline (phen) is a possible approach to circumvent antimicrobial resistance, since it forms very stable complexes known as metalloantibiotics. This work is aimed at determining the antimicrobial activity of metalloantibiotics of Cu(II)FQphen against a panel of multidrug‑resistant (MDR) clinical isolates and to clarify their mechanism of action. Minimum inhibitory concentrations (MICs) were determined against MDR isolates of and methicillin-resistant (MRSA). Metalloantibiotics showed improved antimicrobial activity against several clinical isolates, especially MRSA. Synergistic activity was evaluated in combination with ciprofloxacin and ampicillin by the disk diffusion and checkerboard methods. Synergistic and additive effects were shown against MRSA isolates. The mechanism of action was studied though enzymatic assays and atomic force microscopy (AFM) experiments. The results indicate a similar mechanism of action for FQs and metalloantibiotics. In summary, metalloantibiotics seem to be an effective alternative to pure FQs against MRSA. The results obtained in this work open the way to the screening of metalloantibiotics against other Gram‑positive bacteria.
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http://dx.doi.org/10.3390/ijerph17093127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246690PMC
April 2020

Practical management plan for invasive mosquito species in Europe: I. Asian tiger mosquito (Aedes albopictus).

Travel Med Infect Dis 2020 May - Jun;35:101691. Epub 2020 Apr 22.

Department of Plant and Environment Protection, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia.

Aedes albopictus, also known as the "Asian Tiger Mosquito", is an invasive mosquito species to Europe causing high concern in public health due to its severe nuisance and its vectorial capacity for pathogens such as dengue, chikungunya, yellow fever and Zika. Consequently, the responsible authorities implement management activities to reduce its population density, possibly to below noxious and epidemiological thresholds. In urban areas, these aims are difficult to achieve because of the species' ability to develop in a wide range of artificial breeding sites, mainly private properties. This document (Management Plan) has been structured to serve as a comprehensive practical and technical guide for stakeholders in organizing the vector control activities in the best possible way. The current plan includes coordinated actions such as standardized control measures and quality control activities, monitoring protocols, activities for stakeholders and local communities, and an emergency vector control plan to reduce the risk of an epidemic.
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http://dx.doi.org/10.1016/j.tmaid.2020.101691DOI Listing
June 2021

Comprehensive Periprocedural Transesophageal Echocardiography Is a Key to Success in Transcatheter Mitral Valve Repair.

JACC Case Rep 2020 Apr 15;2(4):555-558. Epub 2020 Apr 15.

Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York.

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http://dx.doi.org/10.1016/j.jaccas.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298787PMC
April 2020

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease.

Sci Rep 2020 03 24;10(1):5306. Epub 2020 Mar 24.

Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.

Mayaro virus (MAYV) is endemic in South American countries where it is responsible for sporadic outbreaks of acute febrile illness. The hallmark of MAYV infection is a highly debilitating and chronic arthralgia. Although MAYV emergence is a potential threat, there are no specific therapies or licensed vaccine. In this study, we developed a murine model of MAYV infection that emulates many of the most relevant clinical features of the infection in humans and tested a live-attenuated MAYV vaccine candidate (MAYV/IRES). Intraplantar inoculation of a WT strain of MAYV into immunocompetent mice induced persistent hypernociception, transient viral replication in target organs, systemic production of inflammatory cytokines, chemokines and specific humoral IgM and IgG responses. Inoculation of MAYV/IRES in BALB/c mice induced strong specific cellular and humoral responses. Moreover, MAYV/IRES vaccination of immunocompetent and interferon receptor-defective mice resulted in protection from disease induced by the virulent wt MAYV strain. Thus, this study describes a novel model of MAYV infection in immunocompetent mice and highlights the potential role of a live-attenuated MAYV vaccine candidate in host's protection from disease induced by a virulent MAYV strain.
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http://dx.doi.org/10.1038/s41598-020-62084-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093544PMC
March 2020

Dengue importation into Europe: A network connectivity-based approach.

PLoS One 2020 12;15(3):e0230274. Epub 2020 Mar 12.

Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Lisbon, Portugal.

The spread of dengue through global human mobility is a major public health concern. A key challenge is understanding the transmission pathways and mediating factors that characterized the patterns of dengue importation into non-endemic areas. Utilizing a network connectivity-based approach, we analyze the importation patterns of dengue fever into European countries. Seven connectivity indices were developed to characterize the role of the air passenger traffic, seasonality, incidence rate, geographical proximity, epidemic vulnerability, and wealth of a source country, in facilitating the transport and importation of dengue fever. We used generalized linear mixed models (GLMMs) to examine the relationship between dengue importation and the connectivity indices while accounting for the air transport network structure. We also incorporated network autocorrelation within a GLMM framework to investigate the propensity of a European country to receive an imported case, by virtue of its position within the air transport network. The connectivity indices and dynamical processes of the air transport network were strong predictors of dengue importation in Europe. With more than 70% of the variation in dengue importation patterns explained. We found that transportation potential was higher for source countries with seasonal dengue activity, high passenger traffic, high incidence rates, high epidemic vulnerability, and in geographical proximity to a destination country in Europe. We also found that position of a European country within the air transport network was a strong predictor of the country's propensity to receive an imported case. Our findings provide evidence that the importation patterns of dengue into Europe can be largely explained by appropriately characterizing the heterogeneities of the source, and topology of the air transport network. This contributes to the foundational framework for building integrated predictive models for bio-surveillance of dengue importation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230274PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067432PMC
July 2020

What happens when we modify mosquitoes for disease prevention? A systematic review.

Emerg Microbes Infect 2020 11;9(1):348-365. Epub 2020 Feb 11.

UEI Parasitologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal.

The release of modified mosquitoes to suppress/replace vectors constitutes a promising tool for vector control and disease prevention. Evidence regarding these innovative modification techniques is scarce and disperse. This work conducted a systematic review, gathering and analysing research articles from PubMed and Biblioteca Virtual em Saúde databases whose results report efficacy and non-target effects of using modified insects for disease prevention, until 2016. More than 1500 publications were screened and 349 were analysed. Only 12/3.4% articles reported field-based evidence and 41/11.7% covered modification strategies' post-release efficacy. Variability in the effective results (90/25.7%) questioned its reproducibility in different settings. We also found publications reporting reversal outcomes 38/10.9%, (e.g. post-release increase of vector population). Ecological effects were also reported, such as horizontal transfer events (54/15.5%), and worsening pathogenesis induced by natural (10/2.9%). Present work revealed promising outcomes of modifying strategies. However, it also revealed a need for field-based evidence mainly regarding epidemiologic and long-term impact. It pointed out some eventual irreversible and important effects that must not be ignored when considering open-field releases, and that may constitute constraints to generate the missing field evidence. Present work constitutes a baseline of knowledge, offering also a methodological approach that may facilitate future updates.
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http://dx.doi.org/10.1080/22221751.2020.1722035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034073PMC
February 2020

[I Submitted a Paper to Acta Médica Portugal. What Happens Now?]

Acta Med Port 2020 Feb 3;33(2):88-89. Epub 2020 Feb 3.

Acta Médica Portuguesa. Ordem dos Médicos. Lisboa. Portugal.

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http://dx.doi.org/10.20344/amp.13373DOI Listing
February 2020

Infective endocarditis: When an image surprises the echocardiographer.

Rev Port Cardiol (Engl Ed) 2019 Nov 6;38(11):831-832. Epub 2020 Feb 6.

Cardiology Department, Centro Hospitalar São João, Porto, Portugal; Faculty of Medicine, Porto University, Porto, Portugal.

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http://dx.doi.org/10.1016/j.repc.2019.01.009DOI Listing
November 2019

Assessment of diastolic function: How much more evidence do we need?

Authors:
Carla Sousa

Rev Port Cardiol (Engl Ed) 2019 Nov 22;38(11):805-807. Epub 2020 Jan 22.

Serviço de Cardiologia, Centro Hospitalar de S. João, EPE, Porto, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.repc.2020.01.003DOI Listing
November 2019

Insect-specific flaviviruses and densoviruses, suggested to have been transmitted vertically, found in mosquitoes collected in Angola: Genome detection and phylogenetic characterization of viral sequences.

Infect Genet Evol 2020 06 10;80:104191. Epub 2020 Jan 10.

Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal; Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal. Electronic address:

This report describes a survey of RNA and DNA viruses carried out in adult mosquitoes from Angola, raised under laboratory conditions from field-collected immature forms. This viral genomic survey was performed using different sets of primers targeting groups of arboviruses with a considerable impact on human health, including flaviviruses, alphaviruses, and phleboviruses. Furthermore, the viral survey that was performed also included detection of densoviruses. The obtained results did not reveal the presence of recognizable pathogenic arboviruses but allowed the identification of insect-specific flaviviruses from two genetic lineages and a single lineage of brevidensoviruses. These viruses, collectivelly detected in Anopheles sp. and Culex pipiens s.l. mosquitoes, were most probably transmitted vertically.
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http://dx.doi.org/10.1016/j.meegid.2020.104191DOI Listing
June 2020

Interaction of polyphenols with model membranes: Putative implications to mouthfeel perception.

Biochim Biophys Acta Biomembr 2020 02 28;1862(2):183133. Epub 2019 Nov 28.

REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.

Food polyphenols in fruits juices, tea, coffee, wine and beer confer sensory properties such as colour, astringency and bitterness. The development of functional healthy drinks without the unpleasant sensory feeling is boosting research for a clearer understanding on the interactions of polyphenols within the oral mucosa. In this study we investigated the interaction of astringent polyphenols, namely ECG, EGCG, procyanidin B4 and PGG, with lipids in model membranes by spectroscopic techniques. The membrane model was built varying the cholesterol content to mimic mouth regions and experiments were conducted at pH 5 to mimic the pH drop at the moment of beverage (e.g. green tea, red wine) intake. Fluorescence quenching results conducted on LUVs with cholesterol molar fractions ranging between 0.34 < χ < 0.74 and similar size distributions (122.9 ± 3.7 nm) showed that interaction of polyphenols is structure- and concentration-dependent. Also, the decrease of partition constants (K) with increasing cholesterol content (χchol) suggest that the affinity of polyphenols is weaker in cholesterol-rich liposomes. STD results revealed that the interaction of EGCG and PGG with membrane lipids involved mainly galloyl residues. Overall, spectroscopic data show that polyphenols interact to higher extent with more polar regions found in buccal, flour of the mouth and gingiva regions than with more hydrophobic regions located in the palate and tongue supporting that lipid microenvironments play a role in oral sensory perception.
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http://dx.doi.org/10.1016/j.bbamem.2019.183133DOI Listing
February 2020

Zika virus threshold determines transmission by European mosquitoes.

Emerg Microbes Infect 2019 ;8(1):1668-1678

Institut Pasteur, Department of Virology, Arboviruses and Insect Vectors, Paris, France.

Since its emergence in Yap Island in 2007, Zika virus (ZIKV) has affected all continents except Europe. Despite the hundreds of cases imported to European countries from ZIKV-infested regions, no local cases have been reported in localities where the ZIKV-competent mosquito is well established. Here we analysed the vector competence of European ( and ) mosquitoes to different genotypes of ZIKV. We demonstrate that from France was less susceptible to the Asian ZIKV than to the African ZIKV. Critically we show that effective crossing of anatomical barriers (midgut and salivary glands) after an infectious blood meal depends on a viral load threshold to trigger: (i) viral dissemination from the midgut to infect mosquito internal organs and (ii) viral transmission from the saliva to infect a vertebrate host. A viral load in body ≥4800 viral copies triggered dissemination and ≥12,000 viral copies set out transmission. Only 27.3% and 18.2% of Montpellier mosquitoes meet respectively these two criteria. Collectively, these compelling results stress the poor ability of to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.
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http://dx.doi.org/10.1080/22221751.2019.1689797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882490PMC
December 2019
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