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OBJECTIVES: Analyze the diagnostic and prognostic value of the sFlt-1/PlGF ratio in pregnant women with at least one sign/symptom of suspected/diagnosed pre-eclampsia. METHODS: This retrospective observational study included 170 pregnant women with at least one sign/symptom of pre-eclampsia, who had sFlt-1/PlGF ratio values. The following information was evaluated: pregnant women's demographic data and clinical history; laboratory data (urine protein/creatinine ratio; sFlt-1/PlGF ratio); signs and symptoms presented; clinical outcome; fetal complications; data related to childbirth. Statistical analysis was performed by R Software Version 3.5.2. RESULTS: Among the 170 patients, 78 presented pre-eclampsia. The median sFlt-1/PlGF ratio was significantly higher [143.1 (2.2-2,927.1)] for women who presented pre-eclampsia than for women without pre-eclampsia [33.5 (0.8-400.2)]. The negative predictive value of sFlt-1/PlGF ratio <38 was 83.9â¯% (95â¯% CI, 71.7-92.4â¯%) and the positive predictive value of sFlt-1/PlGF ratio >85 or 110 (for late onset pre-eclampsia) was 76.4â¯% (95â¯% CI, 66.2-84.8â¯%). sFlt-1/PlGF >85 or 110 was associated with pre-eclampsia clinical development, fetal complications, shorter gestational age at birth, higher number of caesarean deliveries and lower birth weight. CONCLUSIONS: The sFlt-1/PlGF ratio, together with the standard diagnostic criteria, can be used to rule out pre-eclampsia, identify high-risk patients and predict the occurrence of adverse outcomes.
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Pré-Eclâmpsia , Feminino , Humanos , Recém-Nascido , Gravidez , Biomarcadores/metabolismo , Obstetrícia , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Receptor 1 de Fatores de Crescimento do Endotélio VascularRESUMO
INTRODUCTION AND HYPOTHESIS: Vaginal pessaries are used as a conservative treatment for POP in women who do not want or are not candidates for surgery, or as a preliminary step to surgery. Our goals are: evaluate the evolution of patients with advanced POP and repeated expulsion of the pessary, who underwent perineal suture to try to maintain the device. Describe the epidemiological characteristics of patients treated with pessaries in our environment, with or without perineal closure. METHODS: Observational, descriptive and prospective study (October 2016-March 2021) that includes 352 women with advanced-stage POP treated with a pessary, of which 55, after repeated expulsion of the pessary, were treated with a pessary and perineal suture. RESULTS: After pessary insertion associated with perineal closure, 26 patients (47.2%) expelled the pessary and underwent surgery, and 29 (52.8%) kept the device, avoiding surgery. Regarding the women who required perineal suture: The mean age was higher than in the group of patients who did not need this intervention (75.3 vs. 68.3 years), 94.5% had POP ≥ grade III and 100% had a perineal width > 2.5 cm. CONCLUSIONS: Treatment with pessary and perineal closure avoids surgery in women with advanced age and repeated expulsion. Although age should not be an independent factor that limits surgical treatment or the type of intervention, it would be useful to have scales to quantify the frailty of patients, being able to standardize perineal closure in elderly and/or frail women, and in those who do not want or have contraindications for surgery.
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Prolapso de Órgão Pélvico , Pessários , Humanos , Feminino , Idoso , Estudos Prospectivos , Prolapso de Órgão Pélvico/cirurgia , Tratamento Conservador , Suturas , Resultado do TratamentoRESUMO
Introduction: The emergence or persistence of symptoms after acute SARS-CoV-2 infection has made it necessary to develop tools to detect them and assess their impact on patients' quality of life. One of these tools is the COVID-19 Yorkshire Rehabilitation Screening (C19-YRS) scale. We present the results of this tool in a cohort of first pandemic wave patients. Methods: A cross-sectional study of patients with confirmed SARS-CoV-2 infection from March to May 2020 in Lugo (northwestern Spain). C19-YRS was administered via phone 10 months after the acute infection to both former inpatients and outpatients. Electronic medical records were reviewed and relevant data from the acute episode were collected. The main outcome was the presence of impairment in different areas measured by the C19-YRS scale. Results: The answer rate was 63.2%. The mean age was 54 ± 16 years, 38.4% were male and 190 (42.9%) had some comorbidity. Eighty-seven patients (19.6%) required hospitalization and 10 (2.3%) required intensive care unit admission. Ten (3.5%) patients lost their job due to the pandemic. Two hundred seventy-six patients (62.3%) related any symptoms; fatigue (37.2%) and exertional dyspnea (33.4%) were the most common with significant worsening in both cases compared with the situation before the infection. Subgroup analysis showed that more symptom domains were impaired in women than men. Older patients, those with comorbidity and those who needed hospital admission, demanded more health resources after the acute infection. Discussion: C19-YRS is useful for the detection and quantification of symptoms after COVID-19 and provides relevant social, health, and occupational information.
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COVID-19 , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , Pandemias , Espanha , Qualidade de Vida , Estudos TransversaisRESUMO
BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients. METHODS: A prospective cohort study was conducted during two consecutive Influenza seasons (December 2016-March 2017 and December 2017-April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 and May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p < 0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher's test p > 0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient's stratification during seasonal Influenza epidemics.
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Influenza Humana , Linfopenia , Insuficiência Respiratória , Adulto , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/complicações , Linfopenia/complicações , Lactato DesidrogenasesRESUMO
OBJECTIVES: Maternal and fetal complications can occur in pregnant kidney transplant recipients. Since these are high-risk pregnancies, they require a multidisciplinary follow-up to prematurely detect adverse events. Identifying factors that would affect fetal, maternal and graft outcomes is essential to further stratify the risk of pregnant kidney transplant recipients. METHODS: All pregnancies in kidney transplant recipients followed in a single center for 30 years were included. Data included previous transplant information and blood and urine tests performed before pregnancy. Impact of graft function on fetal, maternal and graft outcomes was evaluated. RESULTS: There were 41 pregnancies among 34 patients. Mean gestational age of 35 ± 3 weeks. Caesarean section was performed in 69.4% of patients. Five pregnancies were unsuccessful (12.2%). Four patients suffered an acute graft dysfunction (9.8%) and 12 (29.3%) had a serious maternal hypertensive disorder (preeclampsia, eclampsia or HELLP syndrome). Graft function before pregnancy showed significant correlation with adverse outcomes. CONCLUSIONS: A proteinuria >669 mg/g, serum creatinine >1.75 mg/dL and glomerular filtration rate <36.2 mL/min/1.73 m2 before pregnancy were correlated to graft dysfunction during pregnancy. Similar values of proteinuria were also associated with a risk of maternal hypertensive disorders and pregnancy failure. Therefore, in patients with proteinuria and graft dysfunction, follow-up should be stricter to quickly detect complications.
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Transplante de Rim , Pré-Eclâmpsia , Complicações na Gravidez , Cesárea/efeitos adversos , Creatinina , Feminino , Humanos , Lactente , Rim , Transplante de Rim/efeitos adversos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Resultado da Gravidez/epidemiologiaRESUMO
BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; Pâ =â .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; Pâ =â .003) and lower complicated bacteremia (16.2% vs 32.1%; Pâ =â .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (Pâ =â .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.
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Bacteriemia , Daptomicina , Endocardite , Fosfomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Daptomicina/uso terapêutico , Endocardite/tratamento farmacológico , Fosfomicina/uso terapêutico , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.
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Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Desbridamento , Feminino , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Physiological and biochemical changes occur in pregnancy to nurture the developing fetus. Pregnancy-related experience is unique to every woman. Pregnancy symptoms and complications can range from mild to severe. Many women can lower their risk by performing different therapies. In this context, the present study targets to evaluate the efficacy of integrated yoga consisting of (asanas and pranayama) on pregnancy to reduce the risk of complications. This study is a prospective randomized controlled single-blinded trial with parallel arms: the intervention arm received specific integrated yoga therapy; the control arm received routine standard care from 18 to 22 weeks of gestation until delivery. The incidence of preeclampsia and preterm delivery was lower in the intervention arm. Women in the intervention arm delivered at higher gestational age. Apgar scores and birth weights of neonates were significantly higher in the intervention arm. The findings suggest that yoga is a safe and effective intervention during pregnancy to reduce or prevent pregnancy-related complications. However, further randomized controlled trials are needed to provide firmer evidence regarding the utility and validity of yoga intervention during pregnancy.
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Terapia por Exercício/normas , Resultado do Tratamento , Yoga , Adulto , Terapia por Exercício/métodos , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Resultado da Gravidez/epidemiologia , Estudos ProspectivosRESUMO
Increased life expectancy coupled with decreased birth rates has led to a notable aging of the population. In the social care sector, resources for the older persons should be allocated by means of objective instruments that ensure an appropriate fit between older people's needs and the characteristics of the services. This paper analyzes the appropriacy of actual assignments of resources in a sample of 632 older users of social services, evaluating the degree of fit between these assignments and those made by a Decision Making Model (DMM) which is strictly based on an objective assessment of user's needs and characteristics. The results indicate that biopsychosocial variables included as predictors in the DMM are appropriate for ensuring that the needs of the older persons are met and resources are optimized. However, the current assignments of users to services cannot be explained by relying solely on these variables, suggesting that the allocation of users to services may be conditioned by factors that are different from those covered by the DMM.
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Geriatria/normas , Necessidades e Demandas de Serviços de Saúde/tendências , Expectativa de Vida/tendências , Apoio Social , Serviço Social/tendências , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , HumanosRESUMO
BACKGROUND: Phlomis plants are a source of biological active substances with potential applications in the control of phytopathogens. Phlomis purpurea (Lamiaceae) is autochthonous of southern Iberian Peninsula and Morocco and was found to be resistant to Phytophthora cinnamomi. Phlomis purpurea has revealed antagonistic effect in the rhizosphere of Quercus suber and Q. ilex against P. cinnamomi. Phlomis purpurea roots produce bioactive compounds exhibiting antitumor and anti-Phytophthora activities with potential to protect susceptible plants. Although these important capacities of P. purpurea have been demonstrated, there is no transcriptomic or genomic information available in public databases that could bring insights on the genes underlying this anti-oomycete activity. RESULTS: Using Illumina technology we obtained a de novo assembly of P. purpurea transcriptome and differential transcript abundance to identify putative defence related genes in challenged versus non-challenged plants. A total of 1,272,600,000 reads from 18 cDNA libraries were merged and assembled into 215,739 transcript contigs. BLASTX alignment to Nr NCBI database identified 124,386 unique annotated transcripts (57.7%) with significant hits. Functional annotation identified 83,550 out of 124,386 unique transcripts, which were mapped to 141 pathways. 39% of unigenes were assigned GO terms. Their functions cover biological processes, cellular component and molecular functions. Genes associated with response to stimuli, cellular and primary metabolic processes, catalytic and transporter functions were among those identified. Differential transcript abundance analysis using DESeq revealed significant differences among libraries depending on post-challenge times. Comparative cyto-histological studies of P. purpurea roots challenged with P. cinnamomi zoospores and controls revealed specific morphological features (exodermal strips and epi-cuticular layer), that may provide a constitutive efficient barrier against pathogen penetration. Genes involved in cutin biosynthesis and in exodermal Casparian strips formation were up-regulated. CONCLUSIONS: The de novo assembly of transcriptome using short reads for a non-model plant, P. purpurea, revealed many unique transcripts useful for further gene expression, biological function, genomics and functional genomics studies. The data presented suggest a combination of a constitutive resistance and an increased transcriptional response from P. purpurea when challenged with the pathogen. This knowledge opens new perspectives for the understanding of defence responses underlying pathogenic oomycete/plant interaction upon challenge with P. cinnamomi.
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Perfilação da Expressão Gênica , Genômica , Phlomis/genética , Phlomis/microbiologia , Phytophthora/fisiologia , Ontologia Genética , Anotação de Sequência MolecularRESUMO
An increased knowledge on the real impacts of ectomycorrhizal symbiosis in forest species is needed to optimize forest sustainable productivity and thus to improve forest services and their capacity to act as carbon sinks. In this study, we investigated the response of an oak species to ectomycorrhizae formation using a proteomics approach complemented by biochemical analysis of carbohydrate levels. Comparative proteome analysis between mycorrhizal and nonmycorrhizal cork oak plants revealed no differences at the foliar level. However, the protein profile of 34 unique oak proteins was altered in the roots. Consistent with the results of the biochemical analysis, the proteome analysis of the mycorrhizal roots suggests a decreasing utilization of sucrose for the metabolic activity of mycorrhizal roots which is consistent with an increased allocation of carbohydrates from the plant to the fungus in order to sustain the symbiosis. In addition, a promotion of protein unfolding mechanisms, attenuation of defense reactions, increased nutrient mobilization from the plant-fungus interface (N and P), as well as cytoskeleton rearrangements and induction of plant cell wall loosening for fungal root accommodation in colonized roots are also suggested by the results. The suggested improvement in root capacity to take up nutrients accompanied by an increase of root biomass without apparent changes in aboveground biomass strongly re-enforces the potential of mycorrhizal inoculation to improve cork oak forest resistance capacity to cope with coming climate change.
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Basidiomycota/fisiologia , Micorrizas/fisiologia , Proteínas de Plantas/metabolismo , Raízes de Plantas/microbiologia , Quercus/metabolismo , Quercus/microbiologia , Biomassa , Citoesqueleto/genética , Citoesqueleto/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Metabolismo dos Lipídeos/fisiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , Estresse Fisiológico , SimbioseRESUMO
OBJECTIVES AND DESIGN: Here we evaluated whether allergic rhinitis to Dermatophagoides pteronyssinus induces alterations on circulating B cell subsets. MATERIALS AND METHODS: Circulating B cell subsets and isotype expression on antigen-experienced B cells from allergic patients under conventional pharmacological treatment (NO-SIT, n = 15) and under subcutaneous immunotherapy (SCIT, n = 33), and non-allergic subjects (NC, n = 25) were analyzed by flow cytometry. RESULTS: In allergic patients, we found a significant decrease in IgM(+) and IgG(+) memory B cells and an increase in IgA(+) memory B cells. Additionally, the numbers of circulating IgA(+) plasmablasts in allergic patients were also increased, while those cells expressing IgM were reduced. CONCLUSIONS: Allergic patients have a disturbed B cell subsets distribution which seems to underlie rhinitis pathogenesis and remain unchanged after SCIT.
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Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Adulto , Animais , Estudos de Casos e Controles , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunoterapia , Masculino , Rinite Alérgica/terapiaRESUMO
BACKGROUND: Cork oak (Quercus suber) is one of the rare trees with the ability to produce cork, a material widely used to make wine bottle stoppers, flooring and insulation materials, among many other uses. The molecular mechanisms of cork formation are still poorly understood, in great part due to the difficulty in studying a species with a long life-cycle and for which there is scarce molecular/genomic information. Cork oak forests are of great ecological importance and represent a major economic and social resource in Southern Europe and Northern Africa. However, global warming is threatening the cork oak forests by imposing thermal, hydric and many types of novel biotic stresses. Despite the economic and social value of the Q. suber species, few genomic resources have been developed, useful for biotechnological applications and improved forest management. RESULTS: We generated in excess of 7 million sequence reads, by pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber tissues and organs, developmental stages and physiological conditions. We deployed a stringent sequence processing and assembly pipeline that resulted in the identification of ~159,000 unigenes. These were annotated according to their similarity to known plant genes, to known Interpro domains, GO classes and E.C. numbers. The phylogenetic extent of this ESTs set was investigated, and we found that cork oak revealed a significant new gene space that is not covered by other model species or EST sequencing projects. The raw data, as well as the full annotated assembly, are now available to the community in a dedicated web portal at http://www.corkoakdb.org. CONCLUSIONS: This genomic resource represents the first trancriptome study in a cork producing species. It can be explored to develop new tools and approaches to understand stress responses and developmental processes in forest trees, as well as the molecular cascades underlying cork differentiation and disease response.
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Etiquetas de Sequências Expressas , Quercus/genética , Transcriptoma , DNA de Plantas/análise , Biblioteca Gênica , Filogenia , Quercus/crescimento & desenvolvimento , Análise de Sequência de DNARESUMO
OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.
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Infecções do Sistema Nervoso Central , Infecções Estreptocócicas , Streptococcus bovis , Adulto , Humanos , Sistema Nervoso Central , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/patologia , Infecção Focal/microbiologia , Infecção Focal/patologia , Enteropatias/microbiologia , Enteropatias/patologia , Meningite/microbiologia , Meningite/patologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Streptococcus bovis/fisiologiaRESUMO
BACKGROUND: Chronic urticaria is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, Th17 and Tc17 have been implicated in autoimmune diseases; however, their role in urticaria is not clear yet. METHODS: For the study we recruited 20 patients [10 of them had autoreactive chronic spontaneous urticaria (positive autologous intradermal serum test response, ASST+), and the other 10 were nonautoreactive chronic spontaneous urticaria patients (ASST-)] and 17 healthy age- and gender-matched controls (HG). The frequency and functional activity of Th17/Tc17 and Th1/Tc1 cells were evaluated by flow cytometry and type 2 cytokine mRNA by real-time PCR. RESULTS: Our results demonstrated a significant decrease in Th17 frequency in both chronic urticaria groups compared to HG; regarding the amount of IL-17, at the single cell level, it was reduced in ASST- compared to HG. Concerning the Th1 and Th17 cells producing IFN-γ, IL-2, and TNF-α, a lower frequency was noted in chronic urticaria patients compared to HG. In contrast, a significantly increased frequency of Tc1 cells producing these cytokines was noted in ASST+ compared to HG and ASST-. Also, the frequency of Tc17 cells producing TNF-α was increased in ASST+ compared to HG; however, with respect to the amount of TNF-α, at the single cell level, we found a decrease in ASST+ compared to HG. Regarding type 2 cytokine mRNA, a higher expression was verified in ASST+ compared to HG. CONCLUSION: Our data suggest a probable involvement of cytotoxic T cells, mainly the Tc1 and Tc17 subsets, in chronic urticaria, particularly in the ASST+ group.
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Linfócitos T Citotóxicos/imunologia , Células Th1/imunologia , Células Th17/imunologia , Urticária/imunologia , Adulto , Citocinas/genética , Citocinas/imunologia , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T Citotóxicos/citologia , Células Th1/citologia , Células Th17/citologia , Urticária/sangueRESUMO
UNLABELLED: With the discovery of Th17 cells, it became unclear whether rheumatoid arthritis (RA) is a Th1-mediated and/or a Th17-mediated disease. OBJECTIVE: The aim of this study was to identify and characterize the pro-inflammatory function of IL-17-producing T cell subsets (Th(c)17) in RA. Flow cytometry analysis was performed on peripheral blood from RA patients with inactive or low disease activity (LDA, n = 19) and moderate to high disease activity (HDA, n = 13) to analyze the number and functional activity of Th(c)17 and Th(c)1 cell subsets according to the frequency of IL-2-, TNF-α- and IFN-γ-producers cells, as well as, their cytokine amount. Additionally, 13 age-matched healthy volunteers were added to the study. Our data point to a slight increase in Tc17 frequency in RA patients, more evident in HDA, and a higher ability of Th17 to produce IL-17, whereas a lower production of TNF-α was noted either in Th17 or Tc17 cells, particularly from HDA. A similar decrease was observed in Th(c)1 for almost all studied pro-inflammatory cytokines, with the exception of IL-2, which was increased in Tc1 from LDA patients. Analysing the proportion of pro-inflammatory cytokines-producing cells, a polarization to a Tc1 phenotype seemed to occur in CD8 T cells, while CD4 T cells appear to be decreased in their frequency of IFN-γ-producing cells. Taken together, the functional plasticity features of Th17 and Tc17 cells suggest a particular contribution to the local cytokine production, pointing an underestimated role, namely of Tc1 and Tc17 cells, in the RA pathophysiology.
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Artrite Reumatoide/sangue , Subpopulações de Linfócitos T/patologia , Células Th1/patologia , Células Th17/patologia , Adulto , Artrite Reumatoide/patologia , Contagem de Células , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Phlomis purpurea grows spontaneously in the southern Iberian Peninsula, namely in cork oak (Quercus suber) forests. In a previous transcriptome analysis, we reported on its immunity against Phytophthora cinnamomi. However, little is known about the involvement of secondary metabolites in the P. purpurea defense response. It is known, though, that root exudates are toxic to this pathogen. To understand the involvement of secondary metabolites in the defense of P. purpurea, a metabolome analysis was performed using the leaves and roots of plants challenged with the pathogen for over 72 h. The putatively identified compounds were constitutively produced. Alkaloids, fatty acids, flavonoids, glucosinolates, polyketides, prenol lipids, phenylpropanoids, sterols, and terpenoids were differentially produced in these leaves and roots along the experiment timescale. It must be emphasized that the constitutive production of taurine in leaves and its increase soon after challenging suggests its role in P. purpurea immunity against the stress imposed by the oomycete. The rapid increase in secondary metabolite production by this plant species accounts for a concerted action of multiple compounds and genes on the innate protection of Phlomis purpurea against Phytophthora cinnamomi. The combination of the metabolome with the transcriptome data previously disclosed confirms the mentioned innate immunity of this plant against a devastating pathogen. It suggests its potential as an antagonist in phytopathogens' biological control. Its application in green forestry/agriculture is therefore possible.
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Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.
RESUMO
Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .
Assuntos
Bacteriemia , Fosfomicina , Infecções Estafilocócicas , Adulto , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cloxacilina/efeitos adversos , Fosfomicina/uso terapêutico , Meticilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Resultado do Tratamento , Quimioterapia Combinada/efeitos adversosRESUMO
One of the most remarkable pollination strategy in orchids biology is pollination by sexual deception, in which the modified petal labellum lures pollinators by mimicking the chemical (e.g. sex pheromones), visual (e.g. colour and shape/size) and tactile (e.g. labellum trichomes) cues of the receptive female insect species. The present study aimed to characterize the transcriptional changes occurring after pollination in the labellum of a sexually deceptive orchid (Ophrys fusca Link) in order to identify genes involved on signals responsible for pollinator attraction, the major goal of floral tissues. Novel information on alterations in the orchid petal labellum gene expression occurring after pollination demonstrates a reduction in the expression of alkene biosynthetic genes using O. fusca Link as the species under study. Petal labellum transcriptional analysis revealed downregulation of transcripts involved in both pigment machinery and scent compounds, acting as visual and olfactory cues, respectively, important in sexual mimicry. Regulation of petal labellum senescence was revealed by transcripts related to macromolecules breakdown, protein synthesis and remobilization of nutrients.