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1.
Nat Commun ; 14(1): 3026, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37230979

ABSTRACT

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing a role for an accessory protein in this context.


Subject(s)
COVID-19 , SARS-CoV-2 , Cricetinae , Animals , Humans , Mice , SARS-CoV-2/genetics , Animals, Newborn , Ferrets , Disease Models, Animal , Mesocricetus
2.
bioRxiv ; 2023 Mar 24.
Article in English | MEDLINE | ID: mdl-36238716

ABSTRACT

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets 1, 2 . Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2 3 . Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein in this context.

3.
Nat Commun ; 13(1): 5926, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36319618

ABSTRACT

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.


Subject(s)
Bacteremia , COVID-19 , Coinfection , Gastrointestinal Microbiome , Mice , Animals , Dysbiosis/microbiology , Anti-Bacterial Agents , SARS-CoV-2 , Bacteria
4.
bioRxiv ; 2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35262080

ABSTRACT

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.

5.
Res Sq ; 2021 Jul 27.
Article in English | MEDLINE | ID: mdl-34341786

ABSTRACT

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 that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 97 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 suggest that bacteria 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.

6.
Microorganisms ; 9(7)2021 Jun 27.
Article in English | MEDLINE | ID: mdl-34198973

ABSTRACT

SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale, causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses' structural and functional characteristics, delineating their distinct strategies for efficient spread.

7.
Rev Esp Salud Publica ; 952021 Jun 08.
Article in Spanish | MEDLINE | ID: mdl-34099615

ABSTRACT

Una de las limitaciones para el uso de los Cuestionarios de Calidad de Vida Relacionada con la Salud y de los resultados reportados por pacientes es la dificultad de interpretar los valores obtenidos. La diferencia mínima clínica importante es una medida que ayuda a comprender los resultados de estos cuestionarios y valorar la relevancia clínica del efecto conseguido por la intervención realizada. En este trabajo revisamos el concepto de diferencia mínima clínica importante, describimos los métodos utilizados para su obtención y exponemos sus dificultades, limitaciones y aplicabilidad. Dentro de los resultados reportados por pacientes y, particularmente, en los de calidad de vida, la diferencia mínima clínica importante es una herramienta que ayuda a los clínicos a utilizar correctamente las escalas de medida e interpretar el efecto de las intervenciones. Con este artículo esperamos facilitar la implantación y uso de la diferencia mínima clínica importante y los Cuestionarios de Calidad de Vida Relacionada con la Salud en la práctica habitual con nuestros pacientes.


One of the limitations for the use of Health-related Quality of Life Questionnaires and the results reported by patients is the difficulty of interpreting the values obtained. The minimal important clinical difference is a measure that helps to understand the results of these questionnaires and assess the clinical relevance of the effect achieved by the intervention performed. In this paper, we review the concept of minimal important clinical difference, describe the methods used to obtain it, and expose its difficulties, limitations, and applicability. Within the results reported by patients, and particularly in quality of life, the minimal important clinical difference is a tool that helps clinicians to correctly use the measurement scales and interpret the effect of the interventions. With this article, we hope to facilitate the implementation and use of the minimal important clinical difference and the Health-related Quality of Life Questionnaires in routine practice with our patients.


Subject(s)
Quality of Life , Surveys and Questionnaires , Humans , Spain
8.
J Virol ; 95(7)2021 03 10.
Article in English | MEDLINE | ID: mdl-33622961

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2 cells and validates PF-00835231's early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231's efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549+ACE2 cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-human in vitro models.Importance:The arsenal of SARS-CoV-2 specific antiviral drugs is extremely limited. Only one direct-acting antiviral drug is currently approved, the viral polymerase inhibitor remdesivir, and it has limited efficacy. Thus, there is a substantial need to develop additional antiviral compounds with minimal side effects and alternate viral targets. One such alternate target is its main protease, 3CLpro (Mpro), an essential component of the SARS-CoV-2 life cycle processing the viral polyprotein into the components of the viral polymerase complex. In this study, we characterize a novel antiviral drug, PF-00835231, which is the active component of the first-in-class 3CLpro-targeting regimen in clinical trials. Using 3D in vitro models of the human airway epithelium, we demonstrate the antiviral potential of PF-00835231 for inhibition of SARS-CoV-2.

9.
Scand J Clin Lab Invest ; 81(3): 187-193, 2021 05.
Article in English | MEDLINE | ID: mdl-33591234

ABSTRACT

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.


Subject(s)
COVID-19/diagnosis , Emergency Service, Hospital , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Young Adult
10.
bioRxiv ; 2021 Feb 19.
Article in English | MEDLINE | ID: mdl-32869028

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2 cells and validates PF-00835231's early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231's efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549+ACE2 cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-human in vitro models.

11.
J Virol ; 94(23)2020 11 09.
Article in English | MEDLINE | ID: mdl-32938761

ABSTRACT

SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. In this report, we evaluate type I interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero E6 and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, whereas SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures, we observe the absence of IFN-I stimulation by SARS-CoV-2 alone but detect the failure to counteract STAT1 phosphorylation upon IFN-I pretreatment, resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment postinfection and found that SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame 3b (ORF3b) and genetic differences versus ORF6 suggest that the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development.IMPORTANCE With the ongoing outbreak of COVID-19, differences between SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Interferon Type I/pharmacology , Interferon-alpha/pharmacology , Severe acute respiratory syndrome-related coronavirus/drug effects , Animals , Antiviral Agents/antagonists & inhibitors , Antiviral Agents/metabolism , Betacoronavirus/immunology , Betacoronavirus/physiology , Cell Line , Cell Line, Tumor , Chlorocebus aethiops , Humans , Interferon Type I/antagonists & inhibitors , Interferon Type I/immunology , Interferon Type I/metabolism , Interferon-alpha/antagonists & inhibitors , Interferon-alpha/immunology , Interferon-alpha/metabolism , Phosphorylation , Recombinant Proteins/pharmacology , Severe acute respiratory syndrome-related coronavirus/immunology , Severe acute respiratory syndrome-related coronavirus/physiology , SARS-CoV-2 , STAT1 Transcription Factor/metabolism , Signal Transduction , Vero Cells , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication/drug effects
12.
bioRxiv ; 2020 Jul 13.
Article in English | MEDLINE | ID: mdl-32511335

ABSTRACT

SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. In this report, we evaluate type-I interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, while SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures (HAEC), we observe the absence of IFN-I stimulation by SARS-CoV-2 alone, but detect failure to counteract STAT1 phosphorylation upon IFN-I pretreatment resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment post infection and found SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame (ORF) 3b and changes to ORF6 suggest the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development.

13.
Angew Chem Int Ed Engl ; 59(38): 16770-16776, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32441451

ABSTRACT

The production of hydrogen via water electrolysis is feasible only if effective and stable catalysts for the oxygen evolution reaction (OER) are available. Intermetallic compounds with well-defined crystal and electronic structures as well as particular chemical bonding features are suggested here to act as precursors for new composite materials with attractive catalytic properties. Al2 Pt combines a characteristic inorganic crystal structure (anti-fluorite type) and a strongly polar chemical bonding with the advantage of elemental platinum in terms of stability against dissolution under OER conditions. We describe here the unforeseen performance of a surface nanocomposite architecture resulting from the self-organized transformation of the bulk intermetallic precursor Al2 Pt in OER.

14.
J Clin Psychol ; 76(3): 549-558, 2020 03.
Article in English | MEDLINE | ID: mdl-31714615

ABSTRACT

OBJECTIVE: The purpose of this article was to study the relationship of self-focused attention and dissociation with the dialogical relationship persons diagnosed with psychosis have with their voices. METHOD: The DAIMON Scale was applied to 62 persons diagnosed with psychosis to measure the dialogical relationship with their voices, and the Cambridge depersonalization scale, the Tellegen absorption scale, and the self-focused attention scale. RESULTS: The results showed that the dialogical relationship with the voices was associated with high levels of self-focused attention (private and public), depersonalization, and absorption. It was also found that absorption mediated significantly between public self-focused attention and the dialogical relationship with the voices. CONCLUSIONS: The role of dissociation and self-focused attention in forming the dialogical relationship a person with psychosis has with the voices is discussed and approaches to treatment are suggested.


Subject(s)
Attention , Dissociative Disorders/psychology , Hallucinations/psychology , Psychotic Disorders/epidemiology , Adult , Depersonalization/psychology , Female , Humans , Male , Mediation Analysis , Middle Aged
15.
PLoS Pathog ; 15(11): e1007634, 2019 11.
Article in English | MEDLINE | ID: mdl-31682641

ABSTRACT

Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.


Subject(s)
Antiviral Agents/pharmacology , Gene Expression Regulation/drug effects , Influenza A virus/immunology , Interferon Type I/pharmacology , Nuclear Proteins/metabolism , Orthomyxoviridae Infections/immunology , Transcription Factors/metabolism , Virus Replication/immunology , A549 Cells , Animals , Female , Humans , Immunity, Innate , Influenza A virus/drug effects , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/metabolism , Nuclear Proteins/genetics , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Phosphorylation , STAT1 Transcription Factor , Signal Transduction , Transcription Factors/genetics , Virus Replication/drug effects
16.
Front Plant Sci ; 10: 604, 2019.
Article in English | MEDLINE | ID: mdl-31156674

ABSTRACT

Arbuscular mycorrhizal fungi increase fitness of their host plants under Cu deficient and toxic conditions. In this study, we have characterized two Cu transporters of the CTR family (RiCTR1 and RiCTR2) and a CTR-like protein (RiCTR3A) of Rhizophagus irregularis. Functional analyses in yeast revealed that RiCTR1 encodes a plasma membrane Cu transporter, RiCTR2 a vacuolar Cu transporter and RiCTR3A a plasma membrane protein involved in Cu tolerance. RiCTR1 was more highly expressed in the extraradical mycelia (ERM) and RiCTR2 in the intraradical mycelia (IRM). In the ERM, RiCTR1 expression was up-regulated by Cu deficiency and down-regulated by Cu toxicity. RiCTR2 expression increased only in the ERM grown under severe Cu-deficient conditions. These data suggest that RiCTR1 is involved in Cu uptake by the ERM and RiCTR2 in mobilization of vacuolar Cu stores. Cu deficiency decreased mycorrhizal colonization and arbuscule frequency, but increased RiCTR1 and RiCTR2 expression in the IRM, which suggest that the IRM has a high Cu demand. The two alternatively spliced products of RiCTR3, RiCTR3A and RiCTR3B, were more highly expressed in the ERM. Up-regulation of RiCTR3A by Cu toxicity and the yeast complementation assays suggest that RiCTR3A might function as a Cu receptor involved in Cu tolerance.

17.
Food Chem ; 244: 120-127, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29120759

ABSTRACT

The agronomic production systems may affect the levels of food metabolites. Metabolomics approaches have been applied as useful tool for the characterization of fruit metabolome. In this study, metabolomics techniques were used to assess the differences in phytochemical composition between goldenberry samples produced by organic and conventional systems. To verify that the organic samples were free of pesticides, individual pesticides were analyzed. Principal component analysis showed a clear separation of goldenberry samples from two different farming systems. Via targeted metabolomics assays, whereby carotenoids and ascorbic acid were analyzed, not statistical differences between both crops were found. Conversely, untargeted metabolomics allowed us to identify two withanolides and one fatty acyl glycoside as tentative metabolites to differentiate goldenberry fruits, recording organic fruits higher amounts of these compounds than conventional samples. Hence, untargeted metabolomics technology could be suitable to research differences on phytochemicals under different agricultural management practices and to authenticate organic products.


Subject(s)
Fruit/chemistry , Glycosides/analysis , Metabolomics/methods , Organic Agriculture , Physalis/growth & development , Withanolides/analysis , Agriculture/methods , Ascorbic Acid/analysis , Carotenoids/analysis , Crops, Agricultural/chemistry , Crops, Agricultural/growth & development , Fatty Acids/analysis , Fruit/growth & development , Metabolome , Physalis/chemistry , Phytochemicals/analysis , Principal Component Analysis
18.
Rev. electron ; 40(9)sept. 2015. graf, tab
Article in Spanish | CUMED | ID: cum-65847

ABSTRACT

Fundamento: la Medicina Natural y Tradicional ha ganado un lugar relevante en la terapéutica de múltiples afecciones estomatológicas, siendo los apifármacos, como la tintura de propóleo, ejemplo fehaciente de estos logros.Objetivo: evaluar la efectividad de la tintura de propóleo al 5 por ciento en el tratamiento de la gingivitis descamativa crónica, en pacientes atendidos en la Clínica Estomatológica Docente 3 de Octubre.Métodos: se realizó un estudio cuasi-experimental con pacientes atendidos en la referida clínica estomatológica, en el período de tiempo comprendido entre noviembre de 2012 a noviembre de 2014. El universo estuvo conformado por los 120 pacientes que acudieron a consulta con esta afección, la muestra por 60 pacientes con la enfermedad en su estado activo (agudo), se excluyeron aquellos pacientes que estuvieran recibiendo otro tratamiento. Se evaluaron las variables: tiempo de remisión de las lesiones y la desaparición del dolor, que se evaluó a las 24 horas, 72 horas y a los siete días; curación y efectividad.Resultados: el tiempo de inicio y remisión de los síntomas y signos con el uso del apifármaco fue a las 72 horas. A las 24 horas el 96,6 por ciento clasificó como curados. El tratamiento resultó efectivo para el total de la muestra en estudio. No se reportaron efectos adversos relacionados con el tratamiento.Conclusiones: la tintura de propóleo al 5 por ciento resultó efectiva para el tratamiento de la gingivitis descamativa crónica (AU)


Background: Natural and Traditional Medicine (NTM) has obtained an outstanding place in the therapeutics of multiple stomatology conditions, being the beekeeping drugs, as propolis tincture, a clear example of these achievements.Objective: to evaluate the effectiveness of propolis tincture at 5 percent for the treatment of chronic desquamative gingivitis in patients treated at "3 de octubre" teaching dental clinic.Methods: a quasi-experimental study was carried out with patients treated at the dental clinic mentioned above from November, 2012 to November, 2014. The universe consisted of the 120 patients who came to the clinic suffering from this condition and the sample comprised 60 patients in the acute or active stage of the disease; those patients who were receiving another treatment were excluded. The following variables were assessed: time to remission of the lesions and the disappearance of pain, which was assessed at 24 hours, at 72 hours and at 7 days; healing and effectiveness.Results: the start time and remission of symptoms and signs with the use of beekeeping drugs was at 72 hours. After 24 hours, the 96,6 percent was cured. The treatment was effective for the total study sample. No adverse effects related to the treatment were reported.Conclusions: propolis tincture at 5 percent was effective for the treatment of chronic desquamative gingivitis (AU)


Subject(s)
Humans , Medicine, Traditional , Gingivitis , Propolis
19.
Span. j. psychol ; 17: e20.1-e20.8, ene.-dic. 2014. tab
Article in English | IBECS | ID: ibc-130529

ABSTRACT

The purpose of this work was to study the relationship between self-focused attention and mindfulness in participants prone to hallucinations and others who were not. A sample of 318 healthy participants, students at the universities of Sevilla and Almería, was given the Launay-Slade Hallucinations Scale-revised (LSHS-R, Bentall & Slade, 1985). Based on this sample, two groups were formed: participants with high (n = 55) and low proneness (n = 28) to hallucinations. Participants with a score higher than a standard deviation from the mean in the LSHS-R were included in the high proneness group, participants with a score lower than a standard deviation from the mean in the LSHR-R were included in the second one. All participants were also given the Self-Absorption Scale (SAS, McKenzie & Hoyle, 2008) and the Southampton Mindfulness Questionnaire (SMQ, Chadwick et al., 2008). The results showed that participants with high hallucination proneness had significantly higher levels of public (t(80) = 6.81, p < .001) and private (t(77) = 7.39, p < .001) self-focused attention and lower levels of mindfulness (t(81) = -4.56, p < .001) than participants in the group with low hallucination proneness. A correlational analysis showed a negative association between self-focused attention (private and public) and mindfulness (r = -0.23, p < .001; r = -0.38, p < .001 respectively). Finally, mindfulness was found to partly mediate between self-focused attention and hallucination proneness. The importance of self-focused attention and mindfulness in understanding the etiology of hallucinations discussed and suggest some approaches to their treatment (AU)


No disponible


Subject(s)
Humans , Male , Female , Hallucinations/psychology , Nervous System Diseases/psychology , Psychiatric Status Rating Scales/statistics & numerical data , Psychiatric Status Rating Scales/standards , Mental Disorders/epidemiology , Mental Disorders/prevention & control , Perceptual Disorders/psychology , Surveys and Questionnaires , Psychometrics/methods , Psychometrics/standards , Psychometrics/trends , Data Analysis/methods
20.
Rev. neurol. (Ed. impr.) ; 59(9): 385-391, 1 nov., 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-128863

ABSTRACT

Introducción. Los pacientes con migraña crónica (MC) y abuso de medicación son difíciles de tratar y tienen peor calidad de vida que otros pacientes con migrañas. Objetivo. Valorar si la presencia de abuso de fármacos disminuye la efectividad del topiramato. Pacientes y métodos. Una serie de pacientes con MC fueron agrupados según presentasen criterios de abuso o no abuso de fármacos. Se les aconsejo la supresión del fármaco del cual abusaban. Se ajustó el tratamiento de sus crisis y se inició tratamiento preventivo desde el principio con topiramato. Se valoró el número días con cefalea y migrañas intensas en el mes previo y al cuarto mes de tratamiento. Resultados. Fueron seleccionados 262 pacientes con criterios de MC, y de ellos 167 (63,7%) cumplieron criterios de abuso. En ambos grupos hubo una reducción significativa del número de días con cefalea/mes y numero de crisis de migraña/mes al cuarto mes de tratamiento con topiramato. Porcentaje de reducción de días con cefalea/mes en MC sin abuso, 59,3} 36,1%; y con abuso, 48,7} 41,7% (p = 0,0574). Porcentaje de reducción de migrañas intensas/mes en MC sin abuso, 61,2%; y con abuso, 50% (p = 0,0224). Tasa de respondedores según numero de días con cefalea/mes en MC sin abuso, 69%; y con abuso, 57%. Tasa de respondedores según numero de migrañas intensas/mes en MC sin abuso, 76,8%; y en MC con abuso, 61% (p = 0,0097). Conclusiones. El topiramato fue efectivo en pacientes con MC sin y con abuso de fármacos, aunque con menor efectividad en estos últimos (AU)


Introduction: Patients with chronic migraine (CM) and medication abuse are difficult to treat, and have a greater tendency towards chronification and a poorer quality of life than those with other types of headache. Aim: To evaluate whether the presence of medication abuse lowers the effectiveness of topiramate. Patients and methods: A series of patients with CM were grouped according to whether they met abuse criteria or not. They were advised to stop taking the drug that they were abusing. Treatment was adjusted to match their crises and preventive treatment with topiramate was established from the beginning. The number of days with headache and intense migraine in the previous month and at four months of treatment was evaluated. Results. In all, 262 patients with CM criteria were selected and 167 (63.7%) of them fulfilled abuse criteria. In both groups there was a significant reduction in the number of days with headache/month and number of migraine attacks/month at the fourth month of treatment with topiramate. The percentage of reduction in the number of days with headache/ month in CM without abuse was 59.3} 36.1%, and with abuse, 48.7} 41.7% (p = 0.0574). The percentage of reduction in the number of days with intense migraine/month in CM without abuse was 61.2%, and with abuse, 50% (p = 0.0224). Response rate according to the number of days with headache/month in CM without abuse was 69%, and with abuse, 57%. Response rate according to the number of intense migraines/month in CM without abuse was 76.8%, and in CM with abuse, 61% (p = 0.0097). Conclusions. Topiramate was effective in patients with CM with and without medication abuse, although effectiveness is lower in the latter case (AU)


Subject(s)
Humans , Migraine Disorders/drug therapy , Substance-Related Disorders/complications , Anticonvulsants/therapeutic use , Headache Disorders, Secondary/drug therapy , Premedication , Headache Disorders/drug therapy , Risk Factors
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