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1.
Microorganisms ; 9(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809454

RESUMO

Loop-mediated isothermal amplification allows the rapid, sensitive and specific amplification of DNA without complex and expensive equipment. We compared the diagnostic performance of Loopamp™ Leishmania Detection Kit (Eiken Chemical Co., Ltd., Tokyo, Japan) with conventional and real-time polymerase chain reaction (PCR) for human cutaneous and visceral leishmaniasis caused by L. infantum. A total of 230 DNA samples from cutaneous (CL) and visceral (VL) leishmaniasis cases and controls from Spain, characterized by Leishmania nested PCR (LnPCR) were tested by: (i) the Loopamp™ Leishmania Detection Kit (Loopamp), run on Genie III real-time fluorimeter (OptiGene, UK); and (ii) real-time quantitative PCR (qPCR). The Loopamp test returned 98.8% (95% confidence interval-CI: 96.0-100.00) sensitivity and specificity of 97.7% (95% CI: 92.2-100) on VL samples, and 100% (95% CI: 99.1-100) sensitivity and 100.0% (95% CI: 98.8-100.0) specificity on CL samples. The Loopamp time-to-positivity (Tp) obtained by real-time fluorimetry showed excellent concordance (C = 97.91%) and strong correlation (r = 0.799) with qPCR's cycle threshold (Ct). The performance of Loopamp is comparable to that of LnPCR and qPCR in the diagnosis of cutaneous and visceral leishmaniasis due to L. infantum. The excellent correlation between the Tp and Ct should be further investigated to determine the accuracy of Loopamp to quantify parasite load in tissues.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33802185

RESUMO

The pandemic caused by COVID-19 has generated a transformation in students' competences and university education, especially in the use of digital tools. This study aims to analyze the use of digital tools and social networks of university students during the COVID-19 pandemic. For the collection of information, a validated Likert questionnaire (10-point scale) was adopted. The instrument consisted of a total of 66 items comprising a total of seven dimensions. The sample contained 581 students pursuing degrees in Childhood Education and Primary Education. The analysis of the available information was carried out in two different stages. First, we started by performing an exploratory factorial analysis (EFA) to determine the underlying structure of the Digital Competence of Higher Education Students (DCHES) scale factor. In the second phase, we used SEM (structural equation modeling), a statistical approach to test the relationships between observed and latent variables. More specifically, we estimated a multiple indicators multiple causes (MIMIC) model. The results showed the importance of two of the considered covariates in explaining the variability of the different dimensions of the scale analyzed (DCHES) considering the use of social networks and digital tools of university students. In this sense, both the degree to which virtual tools are used to develop teamwork and the degree of use of YouTube when communicating most fully explained the level of digital skills among the university students studied.

3.
Front Immunol ; 12: 651515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815412

RESUMO

Staphylococcus aureus is the predominant pathogen causing osteomyelitis. Unfortunately, no immunotherapy exists to treat these very challenging and costly infections despite decades of research, and numerous vaccine failures in clinical trials. This lack of success can partially be attributed to an overreliance on murine models where the immune correlates of protection often diverge from that of humans. Moreover, S. aureus secretes numerous immunotoxins with unique tropism to human leukocytes, which compromises the targeting of immune cells in murine models. To study the response of human immune cells during chronic S. aureus bone infections, we engrafted non-obese diabetic (NOD)-scid IL2Rγnull (NSG) mice with human hematopoietic stem cells (huNSG) and analyzed protection in an established model of implant-associated osteomyelitis. The results showed that huNSG mice have increases in weight loss, osteolysis, bacterial dissemination to internal organs, and numbers of Staphylococcal abscess communities (SACs), during the establishment of implant-associated MRSA osteomyelitis compared to NSG controls (p < 0.05). Flow cytometry and immunohistochemistry demonstrated greater human T cell numbers in infected versus uninfected huNSG mice (p < 0.05), and that T-bet+ human T cells clustered around the SACs, suggesting S. aureus-mediated activation and proliferation of human T cells in the infected bone. Collectively, these proof-of-concept studies underscore the utility of huNSG mice for studying an aggressive form of S. aureus osteomyelitis, which is more akin to that seen in humans. We have also established an experimental system to investigate the contribution of specific human T cells in controlling S. aureus infection and dissemination.

4.
Biol Psychol ; 161: 108081, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33757806

RESUMO

Affective and anxiety disorders are the most prevalent and incident psychiatric disorders worldwide. Therapeutic approaches to these disorders using non-invasive brain stimulation (NIBS) and analogous techniques have been extensively investigated. In this paper, we discuss the combination of NIBS and neurofeedback in closed-loop setups and its application for affective symptoms and disorders. For this, we first provide a rationale for this combination by presenting some of the main original findings of NIBS, with a primary focus on transcranial magnetic stimulation (TMS), and neurofeedback, including protocols based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Then, we provide a scope review of studies combining real-time neurofeedback with NIBS protocols in the so-called closed-loop brain state-dependent neuromodulation (BSDS). Finally, we discuss the concomitant use of TMS and real-time functional near-infrared spectroscopy (fNIRS) as a possible solution to the current limitations of BSDS-based protocols for affective and anxiety disorders.

5.
PLoS Negl Trop Dis ; 15(2): e0009126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33524030

RESUMO

The increasing use of immunosuppressants in areas where visceral leishmaniasis (VL) is endemic has increased the number of people susceptible to developing more severe forms of the disease. Few studies have examined the quality of the immune response in immunosuppressed patients or experimental animals with VL. The present work characterises the parasite load developed in, and immune response to, Leishmania infantum-induced VL in C57BL/6 mice that, prior to and during infection, received immunosuppressant treatment with methylprednisolone (MPDN), anti-tumour necrosis factor (anti-TNF) antibodies, or methotrexate (MTX). The latter two treatments induced a significant reduction in the number of CD4+ T lymphocytes over the infection period. The anti-TNF treatment was also associated with a higher parasite load in the liver and a lower parasite load in the spleen. This, plus a possibly treatment-induced reduction in the number of cytokine-producing Th1 cells in the spleen, indicates the development of more severe VL. Interestingly, the MPDN and (especially) MTX treatments provoked a greater presence of soluble Leishmania antigen-specific multi-cytokine-producing T cells in the spleen and a lower liver parasite load than in control animals. These results highlight the need to better understand how immunosuppressant treatments might influence the severity of VL in human patients.

6.
SN Compr Clin Med ; : 1-4, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33585796

RESUMO

In thoracic trauma, many cases may present with hemothorax, and, of those, a portion can complicate in empyema. These cases can reveal themselves to be of difficult management, particularly in peripheral hospitals with complicated access to thoracic surgery. Intrapleural fibrinolytic instillation can be of use and has been widely reported, mostly in the case of empyema. In the literature, the use of fibrinolytics in hemothorax mostly pertained to the older fibrinolytics, such as streptokinase and urokinase. Recent studies describe the use of alteplase in these patients but mostly in the first days after the trauma, when it becomes clear that the first chest tube is not being effective. We report a case of residual traumatic hemothorax that could not be evacuated after multiple chest tubes placements and was finally cleared after instillation of alteplase late in the course of the disease.

8.
Cell Host Microbe ; 29(2): 165-178.e8, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33340449

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) latently infects approximately one-fourth of the world's population. The immune mechanisms that govern progression from latent (LTBI) to active pulmonary TB (PTB) remain poorly defined. Experimentally Mtb-infected non-human primates (NHP) mirror the disease observed in humans and recapitulate both PTB and LTBI. We characterized the lung immune landscape in NHPs with LTBI and PTB using high-throughput technologies. Three defining features of PTB in macaque lungs include the influx of plasmacytoid dendritic cells (pDCs), an Interferon (IFN)-responsive macrophage population, and activated T cell responses. In contrast, a CD27+ Natural killer (NK) cell subset accumulated in the lungs of LTBI macaques. This NK cell population was also detected in the circulation of LTBI individuals. This comprehensive analysis of the lung immune landscape will improve the understanding of TB immunopathogenesis, providing potential targets for therapies and vaccines for TB control.

10.
New Phytol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33368298

RESUMO

Transcription factors (TFs) are key components of the transcriptional regulation machinery. In plants, they accompanied the evolution from unicellular aquatic algae to complex flowering plants that dominate the land environment. The adaptations of the body plan and physiological responses required changes in the biological functions of TFs. Some ancestral gene regulatory networks are highly conserved, while others evolved more recently and only exist in particular lineages. The recent emergence of novel model organisms provided the opportunity for comparative studies, producing new insights to infer these evolutionary trajectories. In this review, we comprehensively revisit the recent literature on TFs of nonseed plants and algae, focusing on the molecular mechanisms driving their functional evolution. We discuss the particular contribution of changes in DNA-binding specificity, protein-protein interactions and cis-regulatory elements to gene regulatory networks. Current advances have shown that these evolutionary processes were shaped by changes in TF expression pattern, not through great innovation in TF protein sequences. We propose that the role of TFs associated with environmental and developmental regulation was unevenly conserved during land plant evolution.

11.
Exp Parasitol ; 220: 108033, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166530

RESUMO

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

12.
J Infect Dis ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175145

RESUMO

BACKGROUND: At the COVID-19 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCW) from Hospital Clínic de Barcelona was 11.2%. METHODS: A follow-up survey one month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed till month 3. RESULTS: At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and the seroprevalence 14.5% (82/565). We found 25 (5%) new infections in participants without previous evidence of infection (501). IgM, IgG and IgA levels declined in 3 months (antibody decay rates 0.15 (95% CI, 0.11; 0.19), 0.66 (95% CI, 0.54; 0.82), 0.12 (95% CI, 0.09; 0.16), respectively), and 68.33% of HCW had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. CONCLUSIONS: Continuous and improved surveillance of SARS-CoV-2 infections in HCW remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels have implications for seroprevalence studies using these isotypes.

13.
J Am Soc Nephrol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148615

RESUMO

BACKGROUND: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS: We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS: We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS: These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.

16.
Front Immunol ; 11: 570661, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101290

RESUMO

Inducible Bronchus Associated Lymphoid Tissue (iBALT) is an ectopic lymphoid tissue associated with severe forms of chronic lung diseases, including chronic obstructive pulmonary disease, rheumatoid lung disease, hypersensitivity pneumonitis and asthma, suggesting that iBALT may exacerbate these clinical conditions. However, despite the link between pulmonary pathology and iBALT formation, the role of iBALT in pathogenesis remains unknown. Here we tested whether the presence of iBALT in the lung prior to sensitization and challenge with a pulmonary allergen altered the biological outcome of disease. We found that the presence of iBALT did not exacerbate Th2 responses to pulmonary sensitization with ovalbumin. Instead, we found that mice with iBALT exhibited delayed Th2 accumulation in the lung, reduced eosinophil recruitment, reduced goblet cell hyperplasia and reduced mucus production. The presence of iBALT did not alter Th2 priming, but instead delayed the accumulation of Th2 cells in the lung following challenge and altered the spatial distribution of T cells in the lung. These results suggest that the formation of iBALT and sequestration of effector T cells in the context of chronic pulmonary inflammation may be a mechanism by which the immune system attenuates pulmonary inflammation and prevents excessive pathology.

17.
Biochem Soc Trans ; 48(5): 1979-1993, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32964920

RESUMO

Synthetic gene circuits allow us to govern cell behavior in a programmable manner, which is central to almost any application aiming to harness engineered living cells for user-defined tasks. Transcription factors (TFs) constitute the 'classic' tool for synthetic circuit construction but some of their inherent constraints, such as insufficient modularity, orthogonality and programmability, limit progress in such forward-engineering endeavors. Here we review how CRISPR (clustered regularly interspaced short palindromic repeats) technology offers new and powerful possibilities for synthetic circuit design. CRISPR systems offer superior characteristics over TFs in many aspects relevant to a modular, predictable and standardized circuit design. Thus, the choice of CRISPR technology as a framework for synthetic circuit design constitutes a valid alternative to complement or replace TFs in synthetic circuits and promises the realization of more ambitious designs.

18.
PLoS Med ; 17(9): e1003282, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32903262

RESUMO

BACKGROUND: Endothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery. METHODS AND FINDINGS: From the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids [MUFAs], and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs [miRNAs] and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval [CI]: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/µl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses. CONCLUSIONS: Our results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937.


Assuntos
Doença das Coronárias/dietoterapia , Endotélio/metabolismo , Idoso , Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Gorduras , Dieta Mediterrânea , Gorduras na Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Azeite de Oliva , Estudos Prospectivos , Proteômica , Método Simples-Cego
19.
Phys Rev Lett ; 125(7): 076402, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32857556

RESUMO

A striking consequence of the Hohenberg-Kohn theorem of density functional theory is the existence of a bijection between the local density and the ground-state many-body wave function. Here we study the problem of constructing approximations to the Hohenberg-Kohn map using a statistical learning approach. Using supervised deep learning with synthetic data, we show that this map can be accurately constructed for a chain of one-dimensional interacting spinless fermions in different phases of this model including the charge ordered Mott insulator and metallic phases and the critical point separating them. However, we also find that the learning is less effective across quantum phase transitions, suggesting an intrinsic difficulty in efficiently learning nonsmooth functional relations. We further study the problem of directly reconstructing complex observables from simple local density measurements, proposing a scheme amenable to statistical learning from experimental data.

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