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1.
Proc Natl Acad Sci U S A ; 120(28): e2301338120, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37399374

RESUMO

Recent fossil discoveries in Western Amazonia revealed that two distinct anthropoid primate clades of African origin colonized South America near the Eocene/Oligocene transition (ca. 34 Ma). Here, we describe a diminutive fossil primate from Brazilian Amazonia and suggest that, surprisingly, a third clade of anthropoids was involved in the Paleogene colonization of South America by primates. This new taxon, Ashaninkacebus simpsoni gen. et sp. nov., has strong dental affinities with Asian African stem anthropoids: the Eosimiiformes. Morphology-based phylogenetic analyses of early Old World anthropoids and extinct and extant New World monkeys (platyrrhines) support relationships of both Ashaninkacebus and Amamria (late middle Eocene, North Africa) to the South Asian Eosimiidae. Afro-Arabia, then a mega island, played the role of a biogeographic stopover between South Asia and South America for anthropoid primates and hystricognathous rodents. The earliest primates from South America bear little adaptive resemblance to later Oligocene-early Miocene platyrrhine monkeys, and the scarcity of available paleontological data precludes elucidating firmly their affinities with or within Platyrrhini. Nonetheless, these data shed light on some of their life history traits, revealing a particularly small body size and a diet consisting primarily of insects and possibly fruit, which would have increased their chances of survival on a natural floating island during this extraordinary over-water trip to South America from Africa. Divergence-time estimates between Old and New World taxa indicate that the transatlantic dispersal(s) could source in the intense flooding events associated with the late middle Eocene climatic optimum (ca. 40.5 Ma) in Western Africa.


Assuntos
Cebidae , Platirrinos , Animais , Filogenia , Brasil , Haplorrinos , Fósseis , Roedores , Evolução Biológica
2.
Am J Med Genet A ; 194(7): e63576, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38407483

RESUMO

Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient's family in which the siblings inherited three different RET 634 genotypes: wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband's deceased mother's paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.


Assuntos
Mutação em Linhagem Germinativa , Mosaicismo , Neoplasia Endócrina Múltipla Tipo 2a , Linhagem , Proteínas Proto-Oncogênicas c-ret , Humanos , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Mutação em Linhagem Germinativa/genética , Feminino , Masculino , Adulto , Substituição de Aminoácidos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Genótipo , Sequenciamento do Exoma
3.
Epilepsy Behav ; 157: 109872, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38870866

RESUMO

PURPOSE: Chronotype, which captures a person's daily preferences for activity and sleep, is still a poorly researched area in epilepsy research. Finding common chronotype characteristics in people with epilepsy (PWE) and explaining possible effects on seizure management are the main goals. METHODS: Eleven large-scale investigations from 2010 to 2023 were examined in this scoping review. These studies included 1.167 PWE and 4.657 control subjects. RESULTS: PWE had intermediate chronotypes more often than not. Adult patients were more morning-oriented overall, while pediatric cohorts were variable. Relationships between chronotype and seizure control were limited since only two studies in adults reported this and those results conflicted. An evening-type chronotype was found to be more common in generalized epilepsy than focal. The relationship of chronotype and specific antiseizure medication (ASM) therapy was not investigated. CONCLUSIONS: The majority of PWE displayed an intermediate chronotype, but analyses based on age showed more nuanced trends, with children displaying variable patterns, adults generally tending toward morningness, and generalized epilepsy being associated with eveningness. This review underscores the importance of more research on the complex connections between epilepsy outcomes and chronotype. It emphasizes the need to study larger samples of PWE with carefully documented seizure control and ASM therapy, including dose and timing of administration to better understand the role of chronotype on epilepsy outcomes.

4.
J Toxicol Environ Health A ; : 1-12, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984907

RESUMO

Dental caries is a highly prevalent oral disease affecting billions of individuals globally. The disease occurs chemically as a result of breakdown of the tooth surface attributed to metabolic activity in colonizing biofilm. Biofilms, composed of exopolysaccharides and proteins, protect bacteria like Streptococcus mutans, which is notable for its role in tooth decay due to its acid-producing abilities. While various antimicrobial agents may prevent biofilm formation, these drugs often produce side effects including enamel erosion and taste disturbances. This study aimed to examine utilization of the Mentha piperita essential oil as a potential antibiofilm activity agent against S. mutans. M. piperita oil significantly (1) reduced bacterial biofilm, (2) exhibited a synergistic effect when combined with chlorhexidine, and (3) did not induce cell toxicity. Chemical analysis identified the essential oil with 99.99% certainty, revealing menthol and menthone as the primary components, constituting approximately 42% and 26%, respectively. Further, M. piperita oil eradicated preformed biofilms and inhibited biofilm formation at sub-inhibitory concentrations. M. piperita oil also interfered with bacterial quorum sensing communication and did not produce any apparent cell toxicity in immortalized human keratinocytes (HaCaT). M. piperita represented an alternative substance for combating S. mutans and biofilm formation and a potential combination option with chlorhexidine to minimize side effects. An in-situ performance assessment requires further studies.

5.
BMC Health Serv Res ; 24(1): 290, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448876

RESUMO

BACKGROUND: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System (BUHS). We describe the implementation of the "Patients with Surgical Indication" (PSI) in a Brazilian public tertiary hospital, the impact on waiting time, and its use in rationing oncological surgeries during the COVID-19 Pandemic. METHODS: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. RESULTS: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (p < 0.01). The same occurred with the backlog that ranged from 6,884 in 2016 to 844 in 2022 (p < 001). During the Pandemic, there was a reduction in the number of non-oncological surgeries per month (95% confidence interval) of -10.9(-18.0;-3.8) during Phase I (January 2019-March 2020), maintenance in Phase II (April 2020-August 2021) 0.1(-10.0;10.4) and increment in Phase III (September 2021-December 2022) of 23.0(15.3;30.8). In the oncological conditions, these numbers were 0.6(-2.1;3.3) for Phase I, an increase of 3.2(0.7;5.6) in Phase II and 3.9(1,4;6,4) in Phase III. CONCLUSION: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.


Assuntos
Pandemias , Listas de Espera , Humanos , Brasil/epidemiologia , Procedimentos Cirúrgicos Eletivos , Hospitais Públicos , Estudos Retrospectivos
6.
World J Microbiol Biotechnol ; 40(8): 248, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904740

RESUMO

This manuscript presents a new report on the in vitro antimicrobial photo-inactivation of foodborne microorganisms (Salmonella spp. and Listeria monocytogenes) using tetra-cationic porphyrins. Isomeric tetra-cationic porphyrins (3MeTPyP, 4MeTPyP, 3PtTPyP, and 4PtTPyP) were tested, and antimicrobial activity assays were performed at specific photosensitizer concentrations under dark and white-light LED irradiation conditions. Among the tested bacterial strains, 4MeTPyP exhibited the highest efficiency, inhibiting bacterial growth within just 60 min at low concentrations (17.5 µM). The minimal inhibitory concentration of 4MeTPyP increased when reactive oxygen species scavengers were present, indicating the significant involvement of singlet oxygen species in the photooxidation mechanism. Furthermore, the checkerboard assay testing the association of 4MeTPyP showed an indifferent effect. Atomic force microscopy analyses and dynamic simulations were conducted to enhance our understanding of the interaction between this porphyrin and the strain's membrane.


Assuntos
Biofilmes , Listeria monocytogenes , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Fármacos Fotossensibilizantes , Porfirinas , Porfirinas/farmacologia , Porfirinas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Biofilmes/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Microbiologia de Alimentos , Antibacterianos/farmacologia , Antibacterianos/química , Microscopia de Força Atômica , Espécies Reativas de Oxigênio/metabolismo , Luz , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química
7.
IEEE Trans Eng Manag ; 71: 6540-6552, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665304

RESUMO

In this article, we extend the innovation literature by examining how firms respond to crisis, specifically exogenous crises. At their early onset, crises may represent a window of opportunity for innovation, but it is not equally allocated across firms. We created a unique database of 636 biopharmaceutical firms, from 24 countries and territories, developing innovative treatments during the early outbreak of the COVID-19 crisis to study this phenomenon. We found that firms acted strategically to the shifting external environment and attempted to capitalize on the opportunity by pursuing different but complementary innovation strategies (i.e., radical versus repurposed). The successful outcome of a chosen strategy was highly dependent upon a firm's accumulated knowledge resources, which varied in degree of diversity (i.e., homogeneous versus heterogeneous). We found that firms with more focused R&D (i.e., homogeneous knowledge) developed more radical innovations, whereas firms with more diverse R&D (i.e., heterogeneous knowledge) repurposed innovations. We controlled for firm size (small versus large), firm age (startup versus mature), and country classification (developing versus emerging). We also controlled for a firm's prior knowledge and expertise in coronavirus research and found that it did not influence innovation. Our results suggest that this unique period of environmental uncertainty and crisis created a window of opportunity and a level playing field for innovation.

8.
Bioinformatics ; 38(4): 1133-1135, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34791062

RESUMO

SUMMARY: minoTour offers a Laboratory Informations Management System (LIMS) system for Oxford Nanopore Technology sequencers, with real-time metrics and analysis available permanently for review. Integration of unique real-time automated analysis can reduce the time required to answer biological questions, including mapping and classification of sequence while a run is in progress. Real-time sequence data require new methods of analysis which do not wait for the completion of a run and minoTour provides a framework to allow users to exploit these features. AVAILABILITY AND IMPLEMENTATION: Source code and documentation are available at https://github.com/LooseLab/minotourcli and https://github.com/LooseLab/minotourapp. Docker images are available from https://hub.docker.com/r/adoni5/, and can be installed using a preconfigured docker-compose script at https://github.com/LooseLab/minotour-docker. An example server is available at http://137.44.59.170. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Nanoporos , Software
9.
Microb Pathog ; 174: 105859, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36403712

RESUMO

Biofilms are responsible for up to 80% of antimicrobial-resistant nosocomial infections. Most of these infections are associated with medical devices such as urinary catheters, and in this context, it is estimated that 90-100% of patients who undergo long-term catheterization develop infections. Proteus mirabilis, the most prevalent microorganism, is responsible for 20-45% of these infections. Thus, this study aimed to evaluate, for the first time, the antimicrobial and antibiofilm effects of cationic porphyrins on P. mirabilis. Neutral porphyrins 3-H2TPyP and 4-H2TpyP and tetra-cationic derivatives 3-cis-PtTPyP and 4-cis-PtTPyP were evaluated in broth microdilution tests to determine the minimum inhibitory and bactericidal concentrations. Time-kill curves, checkerboard test, reactive oxygen species (ROS) scavenger assays, conventional biofilm formation, and biofilm assay with catheters were also performed. The microdilution tests showed greater efficacy against P. mirabilis when 3-cis-PtTPyP was exposed to white-light conditions; this also occurred when the microbial time-kill curve was performed at 0, 2, 6, and 12 h. The radical superoxide species was possibly responsible for photoinactivation in the ROS scavenger assays. In biofilm assays (conventional and catheter), 3-cis-PtTPyP obtained better results when irradiated with a white-light source. In the checkerboard assay, the same compound showed no differences when tested in association with ciprofloxacin hydrochloride. Our findings lead us to conclude that antimicrobial photodynamic therapy and cationic porphyrins obtained positive results and are promising alternatives to treat P. mirabilis biofilms.


Assuntos
Fotoquimioterapia , Porfirinas , Humanos , Proteus mirabilis , Cisplatino/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Antibacterianos/farmacologia , Biofilmes , Porfirinas/farmacologia
10.
Epidemiol Infect ; 151: e63, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37009915

RESUMO

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2-17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0-22.0) in May 2021 to 54.1% (95% CrI 46.7-61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12-17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.


Assuntos
COVID-19 , Humanos , Adolescente , Criança , Pré-Escolar , COVID-19/epidemiologia , North Carolina/epidemiologia , Estudos Prospectivos , SARS-CoV-2 , Estudos Soroepidemiológicos , Anticorpos , Anticorpos Antivirais
11.
J Neuroradiol ; 50(2): 241-252, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36641134

RESUMO

Syphilis is an infectious disease caused by the spirochete Treponema pallidum, subspecies pallidum. Although its incidence has declined after the widespread availability of penicillin, it has recently re-emerged, especially in men who have sex with men and in people living with human immunodeficiency virus (HIV). The neurological manifestations of syphilis, generally known as neurosyphilis, may appear at any time during the infection, including the initial years after the primary infection. Neurosyphilis can be asymptomatic, only with cerebrospinal fluid abnormalities, or symptomatic, characterized by several different clinical syndromes, such as meningitis, gumma, meningovascular, brain parenchyma involvement, meningomyelitis, tabes dorsalis, and peripheral nervous system involvement. However, these syndromes may simulate several other diseases, making the diagnosis often a challenge. In addition, syphilis can also be vertically transmitted from mother to child during pregnancy, leading to neurological manifestations. Neuroimaging is essential to demonstrate abnormal brain or spinal cord findings in patients with neurosyphilis, aiding in the diagnosis, treatment, and follow-up of these patients. This article aims to review the imaging features of neurosyphilis, including the early and late stages of the infection.


Assuntos
Neurossífilis , Minorias Sexuais e de Gênero , Sífilis , Masculino , Criança , Humanos , Feminino , Homossexualidade Masculina , Síndrome , Transmissão Vertical de Doenças Infecciosas , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico
12.
Gen Dent ; 71(2): 65-69, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825976

RESUMO

Plasma preparations originating from the centrifugation of blood samples, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), have proven useful for the treatment of gingival recession due to their rich concentration of cells and cytokines fundamental in the mechanisms of both soft tissue and hard tissue repair. Depending on the preparation method used to generate PRP and PRF, different concentrations of plasma elements and physicochemical characteristics can be obtained. This study sought to perform an integrative literature review to compile the available data on different protocols for generating plasma preparations and their indications, benefits, and results. A descriptive research method was adopted for assessing the literature on processes for obtaining PRF, and articles indexed in the MEDLINE database were searched. The literature review showed that changes in the PRF protocols for obtaining blood concentrates have led to better isolation of cells and growth factors and more promising results in tissue repair. The evolution in protocols has resulted in various forms of PRF with different components: (1) a membrane that aggregates platelets and leukocytes (L-PRF); (2) a PRF rich in growth factors and cytokines, known as advanced PRF (A-PRF); (3) a liquid phase called injectable PRF (I-PRF) that shows greater cell accumulation than L-PRF; (4) A-PRF plus (A-PDF+), which improved the release of growth factors for a period of 10 days; and (5) concentrated PRF (C-PRF) obtained by progressive pipetting, which has the greatest cell accumulation among all of the types of platelet aggregates. Subsequently, the observation that the speed of centrifugation influenced the acquisition of specific cells resulted in the development of the low-speed centrifugation concept. Then, it was determined that reduction of the relative centrifugation forces significantly increased the number of platelets, leukocytes, and growth factors. Recently, evaluation of the centrifugation angle revealed greater entrapment of large cells, such as red blood cells, when centrifugation was changed from a fixed to a horizontal angle. Tissue bioengineering studies are allowing for significant advances in the process of obtaining blood components and enabling their use for tissue repair with greater predictability and less morbidity.


Assuntos
Fibrina Rica em Plaquetas , Plasma Rico em Plaquetas , Humanos , Fibrina Rica em Plaquetas/metabolismo , Leucócitos/metabolismo , Plaquetas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Citocinas/metabolismo
13.
Curr Psychol ; : 1-11, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37359574

RESUMO

The COVID-19 pandemic led to increased mental health concerns among parents. Emerging studies have shown links between COVID-19 vaccine hesitancy and psychological distress, including among parents. The primary aim of this study was to extend these emerging findings by examining the role of COVID-19 vaccine hesitancy in mental health functioning in a national sample of U.S. parents, accounting for the effects of COVID-19 vaccination status and underlying medical conditions increasing COVID-19 risk. A nationally representative sample of U.S. parents (N = 796) completed a cross-sectional survey between February-April 2021, including measures of depressive, anxiety, and COVID-19 acute stress symptoms; COVID-19 vaccination status; underlying medical conditions increasing COVID-19 risk; and COVID-19 vaccine hesitancy. The sample consisted of 51.8% fathers, Mage=38.87 years, 60.3% Non-Hispanic white, 18.1% Hispanic/Latinx, 13.2% Non-Hispanic Black/African American, 5.7% Asian, and 2.8% Other Race. Hierarchical regression models adjusted for demographic covariates revealed that greater COVID-19 vaccination hesitancy and presence of an underlying medical condition were consistently associated with higher levels of depressive, anxiety, and COVID-19 acute stress symptoms among parents. Having had at least one COVID-19 vaccination dose was associated with greater levels of COVID-19 acute stress, but was not associated with depressive or anxiety symptoms. Results add new evidence from the U.S. in support of the link between COVID-19 vaccine hesitancy and psychological distress, point to the potential utility of behavioral health care workers in helping reduce vaccine hesitancy, and provide tentative data suggesting that COVID-19 vaccination for parents alone may not have provided mental health relief.

14.
Exp Parasitol ; 241: 108345, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35985513

RESUMO

Haemonchus contortus is a highly pathogenic and prevalent helminth that causes many deaths in sheep herds. Anthelmintics are usually employed to overcome this issue; however, they do not guarantee immediate and lasting efficacy because of the occurrence of drug-resistant parasites. Among substances that are used in scientific studies for parasitic control, essential oils are known to have different pharmacological properties. However, they demonstrate instability owing to several factors, and therefore, nanoemulsification is considered an alternative to control the instability and degradability of these compounds. The objective of this study was to evaluate the cytotoxicity of nanoemulsions containing essential oil of Eucalyptus globulus against the blood of healthy sheep and to verify their activity against the parasite H. contortus in sheep. The results presented adequate nanotechnological characteristics (diameter 72 nm, PDI 0.2, zeta -11 mV, and acidic pH) and adequate morphology. Further, the corona effect and cytotoxic profiles of the free oil and nanoemulsion against blood cells from healthy sheep were evaluated. The tests results did not present a toxicity profile. For evaluating efficacy, we observed an important anthelmintic action of the nanoemulsion containing oil in comparison to the free oil; the results demonstrate a potential role of the nanoemulsion in the inhibition of egg hatchability and the development of larvae L1 to L3 (infective stage). Based on these results, we developed an important and potential anthelmintic alternative for the control of the parasite H. contortus.


Assuntos
Anti-Helmínticos , Hemoncose , Haemonchus , Óleos Voláteis , Doenças dos Ovinos , Animais , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/toxicidade , Óleo de Eucalipto/farmacologia , Hemoncose/tratamento farmacológico , Hemoncose/parasitologia , Hemoncose/veterinária , Larva , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia
15.
J Med Internet Res ; 24(12): e40035, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36322788

RESUMO

BACKGROUND: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. OBJECTIVE: We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). METHODS: A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis. RESULTS: A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. CONCLUSIONS: CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Reino Unido/epidemiologia
16.
Biofouling ; 37(5): 555-571, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225503

RESUMO

Microbial infections caused by sessile microorganisms are known to be a more challenging issue than infections caused by the same microorganisms in the planktonic state. Pseudomonas aeruginosa is an opportunistic pathogen and biofilm-forming agent. This species presents intense cellular communication mediated by signaling molecules. This process is known as quorum sensing (QS) and induces the transcription of specific genes that favors cell density growth and three-dimensional bacterial grouping. In this context, the discovery of compounds capable of inhibiting the action of the QS signaling molecules seems to be a promising strategy against biofilms. This work aimed to evaluate the anti-biofilm action and the in vitro safety profile of a sulfamethoxazole-Ag complex. The results obtained indicate potential anti-biofilm activity through QS inhibition. In silico tests showed that the compound acts on the las and pqs systems, which are the main regulators of biofilm formation in P. aeruginosa. Additionally, the molecule proved to be safe for human peripheral blood mononuclear cells.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Antibacterianos/farmacologia , Biofilmes , Humanos , Leucócitos Mononucleares , Simulação de Acoplamento Molecular , Prata/farmacologia , Sulfonamidas/farmacologia , Fatores de Virulência
17.
Proc Natl Acad Sci U S A ; 115(15): 3788-3793, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29581293

RESUMO

Heinrich Stadials significantly affected tropical precipitation through changes in the interhemispheric temperature gradient as a result of abrupt cooling in the North Atlantic. Here, we focus on changes in South American monsoon precipitation during Heinrich Stadials using a suite of speleothem records covering the last 85 ky B.P. from eastern South America. We document the response of South American monsoon precipitation to episodes of extensive iceberg discharge, which is distinct from the response to the cooling episodes that precede the main phase of ice-rafted detritus deposition. Our results demonstrate that iceberg discharge in the western subtropical North Atlantic led to an abrupt increase in monsoon precipitation over eastern South America. Our findings of an enhanced Southern Hemisphere monsoon, coeval with the iceberg discharge into the North Atlantic, are consistent with the observed abrupt increase in atmospheric methane concentrations during Heinrich Stadials.


Assuntos
Tempestades Ciclônicas , Camada de Gelo/química , Clima , Isótopos de Oxigênio/análise , Água do Mar/química , América do Sul , Temperatura
18.
J Biol Chem ; 294(25): 9722-9733, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31068415

RESUMO

Bone is a highly metabolic organ that undergoes continuous remodeling to maintain its structural integrity. During development, bones, in particular osteoblasts, rely on glucose uptake. However, the role of glucose metabolism in osteocytes is unknown. Osteocytes are terminally differentiated osteoblasts orchestrating bone modeling and remodeling. In these cells, parathyroid hormone (PTH) suppresses Sost/sclerostin expression (a potent inhibitor of bone formation) by promoting nuclear translocation of class IIa histone deacetylase (HDAC) 4 and 5 and the repression of myocyte enhancer factor 2 (MEF2) type C. Recently, Scriptaid, an HDAC complex co-repressor inhibitor, has been shown to induce MEF2 activation and exercise-like adaptation in mice. In muscles, Scriptaid disrupts the HDAC4/5 co-repressor complex, increases MEF2C function, and promotes cell respiration. We hypothesized that Scriptaid, by affecting HDAC4/5 localization and MEF2C activation, might affect osteocyte functions. Treatment of the osteocytic Ocy454-12H cells with Scriptaid increased metabolic gene expression, cell respiration, and glucose uptake. Similar effects were also seen upon treatment with PTH, suggesting that both Scriptaid and PTH can promote osteocyte metabolism. Similar to PTH, Scriptaid potently suppressed Sost expression. Silencing of HDAC5 in Ocy454-12H cells abolished Sost suppression but not glucose transporter type 4 (Glut4) up-regulation induced by Scriptaid. These results demonstrate that Scriptaid increases osteocyte respiration and glucose uptake by mechanisms independent of HDAC complex inhibition. In osteocytes, Scriptaid, similar to PTH, increases binding of HDAC5 to Mef2c with suppression of Sost but only partially increases receptor activator of NF-κB ligand (Rankl) expression, suggesting a potential bone anabolic effect.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Hidroxilaminas/farmacologia , Osteócitos/metabolismo , Hormônio Paratireóideo/farmacologia , Quinolinas/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Hormônios e Agentes Reguladores de Cálcio/farmacologia , Células Cultivadas , Feminino , Transportador de Glucose Tipo 4/genética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteócitos/citologia , Osteócitos/efeitos dos fármacos
19.
Anal Chem ; 92(8): 5682-5687, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32207608

RESUMO

A simple, rapid, low-cost method was proposed for the imaging of Pseudomonas aeruginosa biofilms on metallic surfaces using an infrared camera. Stainless steel coupons were cooled to generate a thermal gradient in relation to biofilm for active thermography (AT). Both cooling and image acquisition times were optimized and the images obtained with AT were compared with those from scanning electron microscopy. A free software (Thermofilm) was developed for image processing and the results were compared with the software ImageJ, with good agreement (from 87.7 to 103.8%). Images of coupons treated with sanitizer (peracetic acid) were obtained to show the applicability of the proposed method for biofilm studies. All analytical steps could be performed in 3 min in a noncontact, nondestructive, low-cost, portable, and easy-to-use way.


Assuntos
Aço Inoxidável/química , Termografia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Ácido Peracético/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Propriedades de Superfície
20.
Microb Pathog ; 147: 104261, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32422333

RESUMO

Glycerol monolaurate (GML) is composed of lauric acid and glycerol. Research has shown that such organic acids can minimize negative effects caused by mycotoxins. Therefore, the objective of this study was to determine whether adding GML (free or encapsulated) to chick feed minimizes the effects of natural contamination by fumonisin (Fusarium verticillioides), evaluating parameters such as biochemistry, antioxidant properties, histological analysis and chick growth. Were weighed 84 chicks of the Cobb 500 strain and randomly distributed them into six groups of two replicates each (n = 14). The F group consumed feed containing fumonisin (levels 400 ppb), with no performance enhancer; F + ZB- feed with fumonisin (levels 400 ppb) + zinc bacitracin; F + GLM100 - feed with fumonisin (levels 400 ppb) + 100 mg of GML/kg of feed; F + NGLM4 - feed with fumonisin (levels 400 ppb) + 4 mg GML/kg in nanocapsules added to the feed; F + NGLM8 - fumonisin feed (levels 400 ppb) + 8 mg GML/kg in nanocapsules in the feed; and F0 - fumonisin-free feed (negative control) + zinc bacitracin. The body weights of birds fed with feed fumonisin-contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) were significantly lower (P < 0.05) than those of the negative control (F0), despite the use of GML (free and nanoencapsulated). Serum levels of triglycerides, globulins and cholesterol were significantly lower in the F0 group than in the other groups (P < 0.05), except for the F + NGLM8 group. Significantly greater levels of lipid peroxidation were observed in livers in the groups that consumed fumonisin than in the control group (F0) (P < 0.05). Serum levels of reactive oxygen species were significantly lower in groups F + NGLM8 and F0 than in the other treatments (P < 0.05). Superoxide dismutase activity was significantly greater in groups F + NGLM8 and F0 than in groups F, F + ZB and F + NGLM4. Hepatic catalase activity was significantly lower in birds that consumed contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) than in the control group (F0). Greater hepatic glutathione S-transferase activity was observed in the F + NGLM8 group than in the F0 group. Despite changes in cellular lesions in the liver, no histological changes were observed in the liver or intestines, even though visually there was yellowing of the liver. Taken together, the data suggest that free or nano-encapsulated GML did not minimize oxidative stress caused by fumonisin, and consequently, these birds had less weight gain.


Assuntos
Fumonisinas , Ração Animal/análise , Animais , Galinhas , Dieta , Fumonisinas/toxicidade , Fusarium , Lauratos , Fígado , Monoglicerídeos
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