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1.
PLoS Biol ; 20(9): e3001754, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36099266

RESUMO

Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19). Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchoalveolar lavage fluid (BALF) from critically ill COVID-19 patients was associated with reduced intensive care unit (ICU) and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19 , Humanos , Peptidil Dipeptidase A/metabolismo , Receptores Virais , SARS-CoV-2
2.
Am J Epidemiol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38576166

RESUMO

Good adherence to antipsychotic therapy helps prevent relapses in First Episode Psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts to emulate a target trial comparing antipsychotics with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from EUFEST, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone (95% CI) were: 61.5% (52.5-70.6), 73.5% (60.5-84.9), 76.8% (67.2-85.3), 58.4% (40.4-77.4), 76.5% (62.1-88.5), and 74.4% (67.0-81.2) respectively. Compared with aripiprazole, the 12-month risk differences (95% CI) were -15.3% (-30.0, 0.0) for olanzapine, -12.8% (-25.7, -1.0) for risperidone, and 3.0% (-21.5, 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration data sufficed to approximately remove confounding for these clinical questions.

3.
J Exp Bot ; 71(22): 7103-7117, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32856699

RESUMO

To disentangle the role of polygalacturonase (PG) genes in strawberry softening, the two PG genes most expressed in ripe receptacles, FaPG1 and FaPG2, were down-regulated. Transgenic ripe fruits were firmer than those of the wild type when PG genes were silenced individually. Simultaneous silencing of both PG genes by transgene stacking did not result in an additional increase in firmness. Cell walls from ripe fruits were characterized by a carbohydrate microarray. Higher signals of homogalacturonan and rhamnogalacturonan I pectin epitopes in polysaccharide fractions tightly bound to the cell wall were observed in the transgenic genotypes, suggesting a lower pectin solubilization. At the transcriptomic level, the suppression of FaPG1 or FaPG2 alone induced few transcriptomic changes in the ripe receptacle, but the amount of differentially expressed genes increased notably when both genes were silenced. Many genes encoding cell wall-modifying enzymes were down-regulated. The expression of a putative high affinity potassium transporter was induced in all transgenic genotypes, indicating that cell wall weakening and loss of cell turgor could be linked. These results suggest that, besides the disassembly of pectins tightly linked to the cell wall, PGs could play other roles in strawberry softening, such as the release of oligogalacturonides exerting a positive feedback in softening.


Assuntos
Fragaria , Parede Celular/metabolismo , Fragaria/genética , Fragaria/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Pectinas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Poligalacturonase/genética , Poligalacturonase/metabolismo
4.
BMC Cancer ; 19(1): 367, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014287

RESUMO

BACKGROUND: Cervical Cancer is still a major public health challenge in low and middle-income countries. HPV testing has been an innovative approach, which was introduced in Argentina for women aged 30+ through the Jujuy Demonstration Project (JDP) carried out between 2012 and 2014. After a positive HPV-test, cytology is used as triage method. Under this protocol, the group of women with HPV+ and normal cytology are recommended to repeat the test within 12-18 months. Studies have shown that this group has increased risk of CIN2+, however, assuring high levels of repeating test among these women is difficult to achieve. We analyze those factors associated with lower re-test attendance among HPV+/ cytology negative women at a programmatic level in low-middle income settings. METHODS: We used data of women aged 30+ HPV-tested in the JDP and followed until 2018 (n = 49,565). We performed a set of different adjusted logistic regression models. Primary outcomes were re-test attendance and re-test attendance within recommended timeframe. We assessed as covariates age, health insurance status, year of HPV-testing, Pap testing in the past 3 years, HPV-testing modality (clinician-collected (CC) tests/self-collected (SC) tests), and span between HPV-test collection and report of results. RESULTS: Forty nine thousand five hundred sixty five women were HPV-tested and 6742 had a positive HPV-test. Among HPV+ women, a total of 4522 were HPV+/Cytology negative (67.1%). In total, 3172 HPV+/Cytology negative women (70.1%) had a record of a second HPV test as of March 2018. Only 1196 women (26%) completed the second test within the timeframe. Women with no record of a previous Pap (OR: 0.46, 95% CI: 0.4-0.53, p < 0.001), aged 64+ (OR: 0.46, 95% CI: 0.31-0.68, p < 0.001) were less likely to be retested; while women with clinician-collected samples had higher odds of being re-tested (OR: 1.42, 95% CI: 1.06-1.91, p < 0.001). CONCLUSIONS: Low re-test rates were found in HPV +/ normal cytology women. Tailored interventions are needed to increase the effectiveness of the screening in this group, especially for those women with characteristics associated to lower attendance.


Assuntos
Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/psicologia , Infecções por Papillomavirus/complicações , Cooperação do Paciente/estatística & dados numéricos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Argentina/epidemiologia , Citodiagnóstico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Cooperação do Paciente/psicologia , Pobreza , Prognóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologia
5.
J Med Syst ; 42(10): 181, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30155797

RESUMO

Flowcharts used for hospital protocols have a series of ambiguities and limitations in order to express some types of information. In this article, a notation proposal for flowcharts that partially avoids these problems is presented. This new notation is an adaptation of BPMNE2, an extension of the Business Process Model and Notation (BPMN), which allows direct modelling of procedures that follow the Hazard Analysis and Critical Control Points (HACCP) model. The new notation has been validated in the hospital context, specifically in the field of hazardous drugs (HDs). To measure usability from the perspective of the health staff and auditors, the System Usability Scale (SUS) was used. A total of 47 experts took part in the assessment, resulting in a SUS score of 71, that corresponds to an acceptable level of usability. The feedback provided by these participants allows us to discover benefits and drawbacks of the proposal. Also, it is noteworthy that 76.6% of professionals prefer to migrate to the new notation from the ISO 5807:1985 notation, the most commonly used model. In addition to the direct benefits of this notation from the human point of view, its machine-understandable nature provides the required support for its integration into software tools for intelligent monitoring and auditing.


Assuntos
Protocolos Clínicos , Software , Fluxo de Trabalho , Hospitais , Humanos
6.
J Exp Bot ; 67(3): 619-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26585222

RESUMO

Strawberry softening is characterized by an increase in the solubilization and depolymerization of pectins from cell walls. Galactose release from pectin side chains by ß-galactosidase enzymes has been proposed as one reason for the increase in soluble pectins. A putative ß-galactosidase gene, FaßGal4, has been identified using a custom-made oligonucleotide-based strawberry microarray platform. FaßGal4 was expressed mainly in the receptacle during fruit ripening, and was positively regulated by abscisic acid and negatively regulated by auxins. To ascertain the role of FaßGal4 in strawberry softening, transgenic plants containing an antisense sequence of this gene under the control of the CaMV35S promoter were generated. Phenotypic analyses were carried out in transgenic plants during three consecutive growing seasons, using non-transformed plants as control. Two out of nine independent transgenic lines yielded fruits that were 30% firmer than control at the ripe stage. FaßGal4 mRNA levels were reduced by 70% in ripe fruits from these selected transgenic lines, but they also showed significant silencing of FaßGal1, although the genes did not share significant similarity. These two transgenic lines also showed an increase in pectin covalently bound to the cell wall, extracted using Na2CO3. The amount of galactose in cell walls from transgenic fruits was 30% higher than in control; notably, the galactose increase was larger in the 1 M KOH fraction, which is enriched in hemicellulose. These results suggest that FaßGal4 participates in the solubilization of covalently bound pectins during ripening, reducing strawberry fruit firmness.


Assuntos
Parede Celular/metabolismo , Regulação para Baixo , Fragaria/enzimologia , Fragaria/genética , Frutas/enzimologia , Galactose/metabolismo , RNA Antissenso/metabolismo , beta-Galactosidase/genética , Carboidratos/análise , Parede Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Fragaria/efeitos dos fármacos , Frutas/efeitos dos fármacos , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Fenótipo , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Análise de Sequência de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Urônicos/metabolismo , beta-Galactosidase/metabolismo
7.
Crit Rev Food Sci Nutr ; 56(6): 973-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26047907

RESUMO

QR codes opens up the possibility to develop simple-to-use, cost-effective-cost, and functional systems based on the optical recognition of inexpensive tags attached to physical objects. These systems, combined with Web platforms, can provide us with advanced services that are already currently broadly used on many contexts of the common life. Due to its philosophy, based on the automatic recognition of messages embedded on simple graphics by means of common devices such as mobile phones, QR codes are very convenient for the average user. Regretfully, its potential has not yet been fully exploited in the domains of food science and nutrition. This paper points out some applications to make the most of this technology for these domains in a straightforward manner. For its characteristics, we are addressing systems with low barriers to entry and high scalability for its deployment. Therefore, its launching among professional and final users is quite simple. The paper also provides high-level indications for the evaluation of the technological frame required to implement the identified possibilities of use.


Assuntos
Telefone Celular , Computadores de Mão , Processamento Eletrônico de Dados/instrumentação , Rotulagem de Alimentos/métodos , Armazenamento e Recuperação da Informação/métodos , Processamento Eletrônico de Dados/métodos , Humanos , Telecomunicações
8.
Sensors (Basel) ; 16(9)2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27657081

RESUMO

Over recent years, we have witnessed the development of mobile and wearable technologies to collect data from human vital signs and activities. Nowadays, wrist wearables including sensors (e.g., heart rate, accelerometer, pedometer) that provide valuable data are common in market. We are working on the analytic exploitation of this kind of data towards the support of learners and teachers in educational contexts. More precisely, sleep and stress indicators are defined to assist teachers and learners on the regulation of their activities. During this development, we have identified interoperability challenges related to the collection and processing of data from wearable devices. Different vendors adopt specific approaches about the way data can be collected from wearables into third-party systems. This hinders such developments as the one that we are carrying out. This paper contributes to identifying key interoperability issues in this kind of scenario and proposes guidelines to solve them. Taking into account these topics, this work is situated in the context of the standardization activities being carried out in the Internet of Things and Machine to Machine domains.

9.
J Med Syst ; 40(10): 225, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27624494

RESUMO

Procedures from the healthcare domain involve highly critical actions as they may pose a risk for patients' life. Therefore, a large effort is devoted to the standardization in clinical praxis and to the control of quality for these protocols in order to minimize hazards. In this line, this work is compelled to provide an ICT-based support to carry out these controls in a simple and effective manner. Using a methodology based on HACCP and taking advantage of Semantic tools, a holistic platform of services for traceability and control of processes has been designed and implemented. The applied paradigm is based on the use of Control Points as singular points to generate traces using observations and measures relevant for the processes considered. Based on those, it is possible to offer services for advanced querying and knowledge inference. The local deployment just requires regular mobile phones or tablets making this solution cost-effective and easily replicable.


Assuntos
Telefone Celular/instrumentação , Armazenamento e Recuperação da Informação/métodos , Monitorização Fisiológica/instrumentação , Humanos , Telemedicina
10.
Syst Appl Microbiol ; 47(2-3): 126506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38640749

RESUMO

Groundwater offers an intriguing blend of distinctive physical and chemical conditions, constituting a challenge for microbial life. In Mallorca, the largest island of Balearic archipelago, harbours a variety of thermal anomalies (i.e., geothermal manifestation where surface aquifers exhibiting temperatures exceeding the regional average). The metagenomes of two aquifers in the centre and southern of the island showed Pseudomonadota to be the most represented phylum when using extracted 16S rRNA gene sequences. However, the microbial structures within and between aquifers were remarkably diverse but similar in their metabolic profiles as revealed by the metagenome-assembled genomes (MAGs) pointing to a prevalence of aerobic chemolithoautotrophic and heterotrophic metabolisms, especially in the Llucmajor aquifer. Also, some evidences of anaerobic lifestyles were detected, which would indicate that these environments either could suffer episodes of oxygen depletion or the anaerobes had been transported from deeper waters. We believe that the local environmental factors (temperature, external inputs or chemistry) seem to be more relevant than the connection and, eventually, transport of microbial cells within the aquifer in determining the highly divergent structures. Notably, most of the reconstructed genomes belonged to undescribed bacterial lineages and from them two high-quality MAGs could be classified as novel taxa named following the rules of the Code for Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). Accordingly, we propose the new species and genus Costitxia debesea gen. nov., sp. nov., affiliated with the novel family Costitxiaceae fam. nov., order Costitxiales ord. nov. and class Costitxiia class. nov.; and the new new species and genus Lloretia debesea gen. nov. sp. nov. affiliated with the novel family Lloretiaceae fam. nov.


Assuntos
Bactérias , Água Subterrânea , Metagenômica , Filogenia , RNA Ribossômico 16S , RNA Ribossômico 16S/genética , Água Subterrânea/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , Ilhas , Análise de Sequência de DNA , Espanha , Metagenoma , Genoma Bacteriano/genética , Temperatura
11.
mBio ; : e0166724, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037272

RESUMO

Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2- patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2- patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence. IMPORTANCE: The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus, there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection.

12.
Interact J Med Res ; 12: e44135, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37074766

RESUMO

BACKGROUND: Low adherence to healthy habits, which is associated with a higher risk of disease and death, among citizens of Organization for Economic Co-operation and Development countries is a serious concern. The World Health Organization (WHO) and the physical activity (PA) guidelines for Americans provide recommendations on PA and healthy diets. To promote these habits, we suggest using a blockchain-based platform, using the PA Messaging Framework to deliver messages and rewards to users. Blockchain is a decentralized secure platform for data management, which can be used for value-added controls and services such as smart contracts (SCs), oracles, and decentralized applications (dApps). Of note, there is a substantial penetration of blockchain technologies in the field of PA, but there is a need for more implementations of dApps to take advantage of features such as nonfungible tokens. OBJECTIVE: This study aimed to create a comprehensive platform for promoting healthy habits, using scientific evidence and blockchain technology. The platform will use gamification to encourage healthy PA and eating habits; in addition, it will monitor the activities through noninvasive means, evaluate them using open-source software, and follow up through blockchain messages. METHODS: A literature search was conducted on the use of blockchain technology in the field of PA and healthy eating. On the basis of the results of this search, it is possible to define an innovative platform for promoting and monitoring healthy habits through health-related challenges on a dApp. Contact with the user will be maintained through messages following a proposed model in the literature to improve adherence to the challenges. RESULTS: The proposed strategy is based on a dApp that relies on blockchain technology. The challenges include PA and healthy eating habits based on the recommendations of the WHO and the Food and Agriculture Organization. The system is constituted of a blockchain network where challenge-related achievements are stored and verified using SCs. The user interacts with the system through a dApp that runs on their local device, monitors the challenge, and self-authenticates by providing their public and private keys. The SC verifies challenge fulfillment and generates messages, and the information stored in the network can be used to encourage competition among participants. The ultimate goal is to create a habit of healthy activities through rewards and peer competition. CONCLUSIONS: The use of blockchain technology has the potential to improve people's quality of life through the development of relevant services. In this work, strategies using gamification and blockchain are proposed for monitoring healthy activities, with a focus on transparency and reward allocation. The results are promising, but compliance with the General Data Protection Regulation is still a concern. Personal data are stored on personal devices, whereas challenge data are recorded on the blockchain.

13.
Syst Appl Microbiol ; 46(3): 126416, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36965279

RESUMO

Current -omics methods allow the collection of a large amount of information that helps in describing the microbial diversity in nature. Here, and as a result of a culturomic approach that rendered the collection of thousands of isolates from 5 different hypersaline sites (in Spain, USA and New Zealand), we obtained 21 strains that represent two new Salinibacter species. For these species we propose the names Salinibacter pepae sp. nov. and Salinibacter grassmerensis sp. nov. (showing average nucleotide identity (ANI) values < 95.09% and 87.08% with Sal. ruber M31T, respectively). Metabolomics revealed species-specific discriminative profiles. Sal. ruber strains were distinguished by a higher percentage of polyunsaturated fatty acids and specific N-functionalized fatty acids; and Sal. altiplanensis was distinguished by an increased number of glycosylated molecules. Based on sequence characteristics and inferred phenotype of metagenome-assembled genomes (MAGs), we describe two new members of the genus Salinibacter. These species dominated in different sites and always coexisted with Sal. ruber and Sal. pepae. Based on the MAGs from three Argentinian lakes in the Pampa region of Argentina and the MAG of the Romanian lake Fara Fund, we describe the species Salinibacter pampae sp. nov. and Salinibacter abyssi sp. nov. respectively (showing ANI values 90.94% and 91.48% with Sal. ruber M31T, respectively). Sal. grassmerensis sp. nov. name was formed according to the rules of the International Code for Nomenclature of Prokaryotes (ICNP), and Sal. pepae, Sal. pampae sp. nov. and Sal. abyssi sp. nov. are proposed following the rules of the newly published Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). This work constitutes an example on how classification under ICNP and SeqCode can coexist, and how the official naming a cultivated organism for which the deposit in public repositories is difficult finds an intermediate solution.


Assuntos
Bacteroidetes , Ácidos Graxos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Filogenia , Ácidos Graxos/análise , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
14.
Antimicrob Agents Chemother ; 56(12): 6349-57, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23045355

RESUMO

Recent reports have revealed the existence of widespread extensively drug-resistant (XDR) P. aeruginosa high-risk clones in health care settings, but there is still scarce information on their specific chromosomal (mutational) and acquired resistance mechanisms. Up to 20 (10.5%) of 190 bloodstream isolates collected from 10 Spanish hospitals met the XDR criteria. A representative number (15 per group) of isolates classified as multidrug-resistant (MDR) (22.6%), resistant to 1 to 2 classes (moderately resistant [modR]) (23.7%), or susceptible to all antibiotics (multiS) (43.2%) were investigated in parallel. Multilocus sequence typing (MLST) analysis revealed that all XDR isolates belonged to sequence type 175 (ST175) (n = 19) or ST111 (n = 1), both recognized as international high-risk clones. Clonal diversity was higher among the 15 MDR isolates (4 ST175, 2 ST111, and 8 additional STs) and especially high among the 15 modR (13 different STs) and multiS (14 STs) isolates. The XDR/MDR pattern in ST111 isolates correlated with the production of VIM-2, but none of the ST175 isolates produced acquired ß-lactamases. In contrast, the analysis of resistance markers in 12 representative isolates (from 7 hospitals) of ST175 revealed that the XDR pattern was driven by the combination of AmpC hyperproduction, OprD inactivation (Q142X), 3 mutations conferring high-level fluoroquinolone resistance (GyrA T83I and D87N and ParC S87W), a G195E mutation in MexZ (involved in MexXY-OprM overexpression), and the production of a class 1 integron harboring the aadB gene (gentamicin and tobramycin resistance). Of particular interest, in nearly all the ST175 isolates, AmpC hyperproduction was driven by a novel AmpR-activating mutation (G154R), as demonstrated by complementation studies using an ampR mutant of PAO1. This work is the first to describe the specific resistance markers of widespread P. aeruginosa XDR high-risk clones producing invasive infections.


Assuntos
Farmacorresistência Bacteriana/genética , Marcadores Genéticos/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Células Clonais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Eletroforese em Gel de Campo Pulsado , Teste de Complementação Genética , Testes de Sensibilidade Microbiana , Mutação/genética , Reação em Cadeia da Polimerase , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Espanha/epidemiologia
15.
ISME J ; 16(5): 1222-1234, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34887548

RESUMO

Metagenomic surveys have revealed that natural microbial communities are predominantly composed of sequence-discrete, species-like populations but the genetic and/or ecological processes that maintain such populations remain speculative, limiting our understanding of population speciation and adaptation to perturbations. To address this knowledge gap, we sequenced 112 Salinibacter ruber isolates and 12 companion metagenomes from four adjacent saltern ponds in Mallorca, Spain that were experimentally manipulated to dramatically alter salinity and light intensity, the two major drivers of this ecosystem. Our analyses showed that the pangenome of the local Sal. ruber population is open and similar in size (~15,000 genes) to that of randomly sampled Escherichia coli genomes. While most of the accessory (noncore) genes were isolate-specific and showed low in situ abundances based on the metagenomes compared to the core genes, indicating that they were functionally unimportant and/or transient, 3.5% of them became abundant when salinity (but not light) conditions changed and encoded for functions related to osmoregulation. Nonetheless, the ecological advantage of these genes, while significant, was apparently not strong enough to purge diversity within the population. Collectively, our results provide an explanation for how this immense intrapopulation gene diversity is maintained, which has implications for the prokaryotic species concept.


Assuntos
Genoma Bacteriano , Microbiota , Bactérias/genética , Metagenoma , Metagenômica
16.
Artigo em Inglês | MEDLINE | ID: mdl-35805788

RESUMO

Blockchain technology provides a distributed support for information storage and traceability. Recently, it has been booming in a wide variety of domains: finance, food, energy, and health. In the field of physical activity, physical exercise, sport, and active ageing, this technology could also originate some interesting services introducing support for reliable repository of results, for gamification, or for secure data interchange. This systematic review explores the use of blockchain in this context. The objective is to determine to which extent this technology has fulfilled the potential of blockchain to bring these new added-value services. The authors explored 5 repositories in search of papers describing solutions applied to the above-mentioned frame. 17 papers were selected for full-text analysis, and they displayed diverse applications of blockchain, such as Fitness and healthcare, Sport, and Active ageing. A detailed analysis shows that the solutions found do not leverage all the possibilities of blockchain technology. Most of the solutions analyzed use blockchain for managing, sharing, and controlling access to data and do not exploit the possibilities of Smart Contracts or oracles. Additionally, the advantages of the blockchain model have not been fully exploited to engage users using approaches such as gamification.


Assuntos
Blockchain , Registros Eletrônicos de Saúde , Exercício Físico , Tecnologia
17.
Open Forum Infect Dis ; 9(6): ofac083, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35607701

RESUMO

Background: The epidemiology of nosocomial bloodstream infections (NBSIs) in patients with coronavirus disease 2019 (COVID-19) is poorly understood, due in part to substantial disease heterogeneity resulting from multiple potential pathogens. Methods: We identified risk factors for NBSIs and examined the association between NBSIs and mortality in a retrospective cohort of patients hospitalized with COVID-19 in 2 New York City hospitals during the height of the pandemic. We adjusted for the potential effects of factors likely to confound that association, including age, race, illness severity upon admission, and underlying health status. Results: Between January 1 and October 1, 2020, 1403 patients had a positive blood culture, and 79 and 101 met the stringent criteria for NBSI among non-COVID-19 and COVID-19 patients, respectively. NBSIs occurred almost exclusively among patients who were severely ill with COVID-19 at hospital admission. NBSIs were associated with elevated mortality, even after adjusting for baseline differences in COVID-19 illness (55% cases vs 45% controls; P = .13). Mortality was concentrated in patients with early-onset pneumonia caused by S. aureus and gram-negative bacteria. Less virulent Candida (49%) and Enterococcus (12%) species were the predominant cause of NBSI in the latter stages of hospitalization, after antibiotic treatment and COVID-19 treatments that attenuate immune response. Most Enterococcus and Candida infections did not have an identifiable source and were not associated with common risk factors for infection by these organisms. Conclusions: Pathogen species and mortality exhibited temporal differences. Early recognition of risk factors among COVID-19 patients could potentially decrease NBSI-associated mortality through early COVID-19 and antimicrobial treatment.

18.
bioRxiv ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35262080

RESUMO

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

19.
Nat Commun ; 13(1): 5926, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319618

RESUMO

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.


Assuntos
Bacteriemia , COVID-19 , Coinfecção , Microbioma Gastrointestinal , Camundongos , Animais , Disbiose/microbiologia , Antibacterianos , SARS-CoV-2 , Bactérias
20.
Syst Appl Microbiol ; 44(4): 126226, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34171620

RESUMO

In the course of a bioprospective study of marine prokaryotes for cosmetic purposes, four strains, MD_567T, MD_652T, MD_674 and PS_109T, were isolated that 16S rRNA gene affiliation indicated could represent three new species within the family Alteromonadaceae. A thorough phylogenetic, genomic and phenotypic taxonomic study confirmed that the isolates could be classified as three new taxa for which we propose the names Alteromonas antoniana sp. nov., Alteromonas lipotrueae sp. nov. and Alteromonas lipotrueiana sp. nov. In addition, the consistent monophyletic nature of the members of the genera Alteromonas and Salinimonas showed that both taxa should be unified, and therefore we also propose the reclassification of the genus Salinimonas within Alteromonas, as well as new combinations for the species of the former. As the specific epithets profundi and sediminis are already used for Alteromonas species, we created the nomina nova "Alteromonas alteriprofundi" nom. nov. and Alteromonas alterisediminis nom. nov. to accommodate the new names for "Salinimonas profundi" and Salinimonas sediminis. Whole genome comparisons also allowed us to detect the unexpected codification of aromatic hydrocarbon biodegradative compounds, such as benzoate and catechol, whose activity was then demonstrated phenotypically. Finally, the high genomic identity between the type strains of Alteromonas stellipolaris and Alteromonas addita indicated that the latter is a junior heterotypic synonym of Alteromonas stellipolaris.


Assuntos
Alteromonas , Filogenia , Água do Mar/microbiologia , Alteromonadaceae , Alteromonas/classificação , Alteromonas/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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