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1.
J Autoimmun ; 135: 102990, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36621176

RESUMO

OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Inflamação , Citocinas
2.
Exp Appl Acarol ; 89(3-4): 433-445, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37029855

RESUMO

The tick Rhipicephalus microplus is a vector of infectious agents that causes great economic loss in the productivity of cattle herds. Several studies have sought natural compounds with acaricidal activity to control ticks, without allowing the development of resistance, without causing environmental damage, and without presenting toxicity to the hosts. The activity of ozone on the natural biomolecules of living beings has been studied as an alternative to control arthropods and acaricidal effects were shown on ticks. The aim of the present study was to assess the acaricidal effect on larvae and engorged females of R. microplus according to ozone dose. Larvae (n = 377) were distributed in 10 groups and engorged females (n = 284) were distributed in 14 groups. One group was used as control (not exposed to ozone) and the other groups were exposed to ozone gas for 5-105 min. Ozone had a dose-dependent acaricidal effect on both larvae and engorged females. Dosages between 355 and 2130 mg/L min had a delayed acaricidal effect (12-180 h), leading to the death of all engorged females before laying eggs, whereas doses between 3195 and 7455 mg/L min showed immediate acaricidal effect (5 min to 4 h). Doses between 1775 and 6390 mg/L min had an immediate (up to 5 min) acaricidal effect on the larvae of this species. Further studies should consider longer follow-up times during the assessment of the acaricidal activity against ticks.


Assuntos
Acaricidas , Rhipicephalus , Feminino , Animais , Bovinos , Acaricidas/farmacologia , Larva
3.
Nutr Neurosci ; 25(8): 1680-1696, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33650943

RESUMO

BACKGROUND: Noncommunicable diseases (NCDs) lead to drastic metabolic alterations with associated energy balance and body weight changes, two related physiological processes regulated by the brain. Polyphenol-based treatments for NCDs have emerged as a promising therapy, which seems to involve the energy balance modulation. However, it remains unclear what the most effective polyphenols-based treatment is to attenuate adverse effects in the energy balance of NCDs. OBJECTIVES: This systematic review aimed to evaluate the literature on the metabolic and neurological effects of polyphenols-based treatment in rodent models of NCDs. METHODS: Literature search was carried out in the following databases: CINAHL, Medline/PubMed, SCOPUS, and Web of Science. For title and abstract screening, original papers with polyphenols exposure in rodents were selected. For full-text screening, studies with models of NCDs that reported metabolic and neurological outcomes when treated with polyphenols were selected for inclusion in this review. RESULTS: 23 articles, using individual compound (11 articles) or polyphenols extracts (12 articles), were included in this review: 5 articles using tea polyphenols, 12 articles using grape-derived polyphenols, 3 articles using the polyphenol quercetin, and 3 articles using other polyphenol sources. Most results agree on the beneficial effect of polyphenols in attenuating alterations in energy balance and body weight. Such effects were associated with neuroprotective responses in different brain areas including hippocampus and hypothalamus. CONCLUSION: In conclusion, this review shows that the treatment with polyphenols, especially resveratrol or quercetin, attenuates the adverse effects of NCDs on energy balance and are associated with neuroprotective effects.


Assuntos
Doenças não Transmissíveis , Polifenóis , Animais , Peso Corporal , Polifenóis/farmacologia , Quercetina , Roedores
4.
Climacteric ; 25(4): 407-412, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35440244

RESUMO

OBJECTIVE: This study aimed to verify the presence of polymorphism rs2165241 of the lysyl oxidase-like 1 (Loxl1) gene and its association with pelvic organ prolapse (POP) in Brazilian women and determine risk factors for POP development. METHODS: The study was previously approved by the local research and ethics board. Postmenopausal women were included and divided into POP (stages III and IV) and control (stages 0 and I) groups. Peripheral blood samples were collected, and the DNA sequence of interest was analyzed by real-time reverse-transcriptase polymerase chain reaction. We used logistic regression and considered a recessive model of inheritance for the analysis, with p < 0.05 for significance. RESULTS: A total of 836 women were assessed: 426 POP cases and 410 controls. The frequencies of CC, CT and TT genotypes were similar in both groups. Age (odds ratio [OR] = 1.1, 95% confidence interval [CI] = 1.07; 1.14), number of vaginal births (OR = 17.06, 95% CI = 5.94; 48.97), family history (OR = 2.87, 95% CI = 1.57; 5.22) and weight of largest newborn (OR = 1.001, 95% CI = 1.0003; 1.001) were independent risk factors for POP, while multiple cesarean sections (two or more) was protective (OR = 0.17, 95% CI = 0.07; 0.42). CONCLUSION: No association was detected between rs2165241 of the Loxl1 gene and POP.


Assuntos
Prolapso de Órgão Pélvico , Pós-Menopausa , Aminoácido Oxirredutases/genética , Feminino , Humanos , Recém-Nascido , Prolapso de Órgão Pélvico/genética , Polimorfismo Genético , Pós-Menopausa/genética , Gravidez , Vagina
5.
Med Mycol ; 59(8): 749-762, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-33550415

RESUMO

Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of ß-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a ß-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of ß-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy. LAY SUMMARY: We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice.


Assuntos
Paracoccidioides/imunologia , Paracoccidioidomicose/tratamento farmacológico , Fagócitos/efeitos dos fármacos , Zimosan/farmacologia , Animais , Camundongos , Paracoccidioides/patogenicidade , Paracoccidioidomicose/imunologia , Fagócitos/imunologia , Virulência , Zimosan/uso terapêutico
6.
Epidemiol Infect ; 149: e60, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629938

RESUMO

The objective of this study was to analyse the dynamics of spatial dispersion of the coronavirus disease 2019 (COVID-19) in Brazil by correlating them to socioeconomic indicators. This is an ecological study of COVID-19 cases and deaths between 26 February and 31 July 2020. All Brazilian counties were used as units of analysis. The incidence, mortality, Bayesian incidence and mortality rates, global and local Moran indices were calculated. A geographic weighted regression analysis was conducted to assess the relationship between incidence and mortality due to COVID-19 and socioeconomic indicators (independent variables). There were confirmed 2 662 485 cases of COVID-19 reported in Brazil from February to July 2020 with higher rates of incidence in the north and northeast. The Moran global index of incidence rate (0.50, P = 0.01) and mortality (0.45 with P = 0.01) indicate a positive spatial autocorrelation with high standards in the north, northeast and in the largest urban centres between cities in the southeast region. In the same period, there were 92 475 deaths from COVID-19, with higher mortality rates in the northern states of Brazil, mainly Amazonas, Pará and Amapá. The results show that there is a geospatial correlation of COVID-19 in large urban centres and regions with the lowest human development index in the country. In the geographic weighted regression, it was possible to identify that the percentage of people living in residences with density higher than 2 per dormitory, the municipality human development index (MHDI) and the social vulnerability index were the indicators that most contributed to explaining incidence, social development index and the municipality human development index contributed the most to the mortality model. We hope that the findings will contribute to reorienting public health responses to combat COVID-19 in Brazil, the new epicentre of the disease in South America, as well as in other countries that have similar epidemiological and health characteristics to those in Brazil.


Assuntos
COVID-19/diagnóstico , Pandemias/estatística & dados numéricos , Teorema de Bayes , Brasil/epidemiologia , COVID-19/epidemiologia , Cidades/epidemiologia , Humanos , Incidência , Modelos Lineares , Pandemias/prevenção & controle , Fatores de Risco , Fatores Socioeconômicos , Análise Espacial
7.
J Eur Acad Dermatol Venereol ; 35(11): 2128-2142, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34263958

RESUMO

Keloids (K) and hypertrophic scars (HS) are abnormal responses to wound healing that occur as the result of dermal inflammation. Despite the advances on their treatment, many patients still suffer from the negative effects of excessive scarring; its approach is impaired by the lack of objective data on different treatments and the large genetic variability among patients and the difficulties in producing multicentre studies. Their incidence among the Brazilian population is high, as the result of an admixture of Amerindians, Europeans and Africans ancestral roots. With the aim of producing multicentre studies on K and HS, a panel of senior Brazilian dermatologists focused on their treatment was invited to contribute with the K and HS Treatment Brazilian Guidelines. In the first part of this study, different treatment modalities for keloids and HS are fully reviewed by the panel. The second part of the study presents a consensus recommendation of treatment for different types of lesions. More than a literature review, this article aims to show the pitfalls and pearls of each therapeutic option, as well as a therapeutic approach by the Panel of Experts on keloids and Scars on a highly mixed population, providing simple guidelines.


Assuntos
Cicatriz Hipertrófica , Queloide , Brasil , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/terapia , Humanos , Queloide/genética , Queloide/patologia , Queloide/terapia
8.
Ann Oncol ; 31(12): 1734-1745, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32976938

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. PATIENTS AND METHODS: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. RESULTS: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73-1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1-4.2), compared with 3.4 (2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8-19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74-1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. CONCLUSION: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.


Assuntos
Mesotelioma Maligno , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia
9.
J Sex Med ; 17(8): 1495-1508, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32622766

RESUMO

BACKGROUND: Approximately 43% of Spanish men report experiencing premature ejaculation (PE) at some point in their lives and 12.1% suffer from erectile dysfunction (ED), of whom only 16.5% have seen a doctor. Despite this, ED and PE remain undiagnosed among a supposedly healthy segment of the population. AIM: To assess the general knowledge of a representative population of healthy Spanish males of the symptoms, treatment, and expectations related to ED and PE. METHODS: This was a descriptive study based on an online questionnaire in which 2,515 males aged 25-75 years with no history of ED and/or PE presented their perception of aspects related to symptoms, diagnosis, treatment, and expectations in ED and PE. MAIN OUTCOME MEASURES: The study provided an evaluation of the knowledge, attitude, and underdiagnosis of ED and/or PE in healthy males and the approach taken by urology specialists and other disciplines. RESULTS: The survey was completed by 2,515 healthy males, including over 80% of those who had completed secondary or higher education. 60% of the sample had never seen a urologist and 59% and 62% of the participating men responded correctly to the statements about PE and ED, respectively. Their lack of knowledge of the therapeutic alternatives was clear (74% and 76% of the panel were unaware of the existence of effective treatments for ED and PE, respectively). Despite the initiative shown by some participants in seeking information about each condition (10.3% for ED; 16.7% for PE), only 4.7% of them had been questioned about ED by a medical practitioner (1.9% for PE). The underdiagnosis rate stood at 3.5% for ED (5.6% participants >65 years) and at about 10% for PE. CLINICAL IMPLICATIONS: These results will represent a point of departure for establishing some recommendations to improve the detection and treatment of these disorders. STRENGTHS & LIMITATIONS: This is the first study of its kind in Spain to analyze the underdiagnosis of ED and/or PE inferred from data reported by a population of healthy males. Screening for ED was performed with a validated questionnaire. However, the rest of the research was conducted using adaptations of validated questionnaires or a self-designed questionnaire based on and in consultation with a group of experienced andrologists. CONCLUSION: People need to have greater knowledge of both the conditions and the related false myths to make sure that they are familiar with the existence of drug treatments and socio-sanitary interventions. Primary care physicians and urologists should also be more proactive in routine visits in order to achieve better management of ED and PE. Prieto-Castro R, Puigvert-Martínez AM, Artigas-Feliu R, et al. Opinions, Attitudes, and Perceptions in Relation to Erectile Dysfunction and Premature Ejaculation in the Undiagnosed Spanish Male Population. Results of the PANDORA Project. J Sex Med 2020;17:1495-1508.


Assuntos
Disfunção Erétil , Ejaculação Precoce , Adulto , Idoso , Atitude , Ejaculação , Disfunção Erétil/diagnóstico , Disfunção Erétil/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Ejaculação Precoce/diagnóstico , Ejaculação Precoce/epidemiologia , Espanha/epidemiologia , Inquéritos e Questionários
10.
Med Mycol ; 58(2): 227-239, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095342

RESUMO

Current antifungal drugs present poor effectiveness and there is no available vaccine for fungal infections. Thus, novel strategies to treat or prevent invasive mycosis, such as cryptococcosis, are highly desirable. One strategy is the use of immunomodulators of polysaccharide nature isolated from mushrooms. The purpose of the present work was to evaluate the immunostimulatory activity of ß-(1,3)-glucan-containing exopolysaccharides (EPS) from the edible mushrooms Auricularia auricula in phagocytes and mice infected with Cryptococcus neoformans. EPS triggered macrophages and dendritic cell activation upon binding to Dectin-1, a pattern recognition receptor of the C-type lectin receptor family. Engagement of Dectin-1 culminated in pro-inflammatory cytokine production and cell maturation via its canonical Syk-dependent pathway signaling. Furthermore, upon EPS treatment, M2-like phenotype macrophages, known to support intracellular survival and replication of C. neoformans, repolarize to M1 macrophage pattern associated with enhanced production of the microbicidal molecule nitric oxide that results in efficient killing of C. neoformans. Treatment with EPS also upregulated transcript levels of genes encoding products associated with host protection against C. neoformans and Dectin-1 mediated signaling in macrophages. Finally, orally administrated ß-glucan-containing EPS from A. auricular enhanced the survival of mice infected with C. neoformans. In conclusion, the results demonstrate that EPS from A. auricula exert immunostimulatory activity in phagocytes and induce host protection against C. neoformans, suggesting that polysaccharides from this mushroom may be promising as an adjuvant for vaccines or antifungal therapy.


Assuntos
Agaricales/química , Criptococose/prevenção & controle , Polissacarídeos Fúngicos/imunologia , Fagócitos/efeitos dos fármacos , Fagócitos/imunologia , beta-Glucanas/imunologia , Animais , Criptococose/imunologia , Cryptococcus neoformans/imunologia , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Fatores Imunológicos/farmacologia , Lectinas Tipo C/imunologia , Pneumopatias Fúngicas , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Fagócitos/microbiologia , Transdução de Sinais , beta-Glucanas/farmacologia
11.
BMC Infect Dis ; 20(1): 186, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111168

RESUMO

BACKGROUND: The presentation of clinical leptospirosis has been historically associated with animal workers, slaughterhouse workers and medical veterinarians. This association has shifted to be related to flooding events and outdoor activities; few cases are related to high-risk factors found in immunosuppressed patients. Scarcely a handful of cases have serological evidence of immune response against Leptospira serovar Bratislava representing serogroup Australis, a serovar associated with poor reproductive performance in swine and horses, and recently with cats. CASE PRESENTATION: Herein, we describe a rare clinical presentation of disseminated Leptospira infection in an immunosuppressed 65-year-old woman. She was admitted to the emergency room with fever, bacteraemia, bilateral uveitis and pulmonary involvement. The patient denied outdoor activities; she only had wide exposure to faeces and urine from cats living in her home. Her medical history included idiopathic thrombocytopenic purpura (ITP) diagnosed at the age of 18. She did not respond to medical treatment, and a splenectomy was performed. At age 60, she was diagnosed with Chronic Myeloid Leukemia (CML), and was treated with a tyrosine kinase inhibitor (TKI) -Imatinib. The patient voluntarily discontinued the treatment for the last 6 months. After extensive workup, no microorganisms were identified by the commonly used stains in microbiology. The diagnosis was performed through dark-field microscopy, microagglutination test (MAT), Leptospira genus-specific PCR, the IS1500 PCR for identification of pathogenic species, and 16S based sequencing for the genus identification. CONCLUSION: Immunosuppressed patients may acquire uncommon infections from ubiquitous microorganisms. In this case, serology evidence of exposure to Leptospira serovar Bratislava by MAT and the presence of the Leptospira genus were identified. It should be on mind for the diagnosis in otherwise healthy patients, and thoroughly search on splenectomised patients exposed to animals. Additionally, this report highlights the usefulness of PCR for diagnosis of this potentially life-threatening illness.


Assuntos
Bacteriemia/diagnóstico , Leptospirose/diagnóstico , Idoso , Bacteriemia/microbiologia , DNA Bacteriano/metabolismo , Feminino , Humanos , Hospedeiro Imunocomprometido , Leptospira/genética , Leptospira/isolamento & purificação , Leptospirose/microbiologia , Pneumonia por Mycoplasma/diagnóstico , Insuficiência Respiratória/diagnóstico , Esplenectomia , Tórax/diagnóstico por imagem , Uveíte/diagnóstico
12.
J Appl Microbiol ; 129(5): 1297-1308, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32463948

RESUMO

AIMS: To evaluate the ability of the haloarchaeon Haloferax volcanii to produce Ag and Au nanoparticles (NPs) and to characterize the obtained material in order to find relevant properties for future potential applications. METHODS AND RESULTS: Nanoparticles were produced by incubating H. volcanii cells with the corresponding metal salt. In the presence of precursor salts, cultures evidenced a colour change associated to the formation of metallic nanostructures with plasmonic bands located in the visible range of the spectrum. X-ray fluorescence analysis confirmed the presence of Ag and Au in the NPs which were spherical, with average sizes of 25 nmol l-1 (Ag) and 10 nmol l-1 (Au), as determined by electronic microscopy. Fourier transformed infrared spectroscopy indicated that both types of NPs showed a stable protein capping. Ag NPs evidenced antibacterial activity and Au NPs improved the specificity of polymerase chain reaction reactions. Au and Ag NPs were able to reduce 4-nitrophenol when incubated with NaBH4 . CONCLUSIONS: Haloferax volcanii is able to synthesize metallic NPs with interesting properties for technological applications. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data demonstrate the ability of H. volcanii to synthesize metal NPs and constitutes a solid starting point to deepen the study and explore novel applications.


Assuntos
Ouro/metabolismo , Haloferax volcanii/metabolismo , Nanopartículas Metálicas/microbiologia , Prata/metabolismo , Antibacterianos/biossíntese , Antibacterianos/química , Antibacterianos/farmacologia , Boroidretos/metabolismo , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Nitrofenóis/metabolismo , Tamanho da Partícula , Prata/química , Prata/farmacologia
13.
J Eur Acad Dermatol Venereol ; 34(5): 1080-1091, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31587379

RESUMO

BACKGROUND: Perineural invasion (PNI) is a feature of poor prognosis in cutaneous squamous cell carcinoma (CSCC). The benefit of postoperative radiotherapy (PORT) in the management of CSCC with PNI is still not well established. OBJECTIVES: We aimed to evaluate the usefulness of PORT in the treatment of CSCC with PNI so as to determine which patients would best benefit from this type of treatment. METHODS: A retrospective multicenter cohort of 110 CSCCs with PNI was evaluated. Eighteen recurrent cases were excluded for subsequent analysis. We searched for the types of PNI associated with poor outcome and analysed the effectiveness of PORT on different groups of CSCC with PNI. We also assessed for the usefulness of PORT depending on the surgical margin status (either clear or positive). RESULTS: Postoperative radiotherapy showed clear benefit over observation in CSCC with PNI and positive margins after surgery, where the management by observation increased the risk of poor outcome events 2.43 times (P = 0.025), and especially in those with positive margins and PNI ≥0.1 mm, where the risk of poor prognosis is eight times greater following a management by observation (P = 0.0065). Multivariate competing risk analysis preserved statistical significance. CONCLUSIONS: The use of PORT on patients with CSCC with PNI and positive margins after surgery, especially in PNI ≥0.1 mm, significantly improves long-term outcome. The benefit of PORT in cases with clear margins is not as evident, especially in those with PNI of small-calibre nerves. Clinical trials are imperative.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Humanos , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia
14.
J Dairy Sci ; 103(5): 4100-4108, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32197850

RESUMO

Staphylococcus aureus is one of the main causative agents of food poisoning. This bacterium is an important component of cheese microbiota and plays an important role in foodborne diseases. Another important component of the microbiota is the lactic acid bacterium, which actively participates in processes that define the physicochemical, sensorial, and microbiological features of cheese. Of the various microbiological interactions in cheese, the interaction between lactic acid bacteria and Staph. aureus is most relevant. To this end, we evaluated the viability of Staph. aureus strains and the expression of their enterotoxins in cheeses produced experimentally, using Weissella paramesenteroides GIR16L4 or Lactobacillus rhamnosus D1 or both as starter cultures. Over 7 d, we observed that the presence of lactic acid bacteria did not impair Staph. aureus growth. However, via qPCR we observed a change in the gene expression of staphylococcal enterotoxins, suggesting that molecular communication exists between Staph. aureus strains and lactic acid bacteria in cheese.


Assuntos
Toxinas Bacterianas/metabolismo , Queijo/microbiologia , Enterotoxinas/metabolismo , Lacticaseibacillus rhamnosus/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Superantígenos/metabolismo , Weissella/crescimento & desenvolvimento , Animais , Toxinas Bacterianas/genética , Queijo/análise , Enterotoxinas/genética , Microbiologia de Alimentos , Lactobacillales/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Leite , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Superantígenos/genética , Transcriptoma , Weissella/metabolismo
15.
J Dairy Sci ; 103(3): 2098-2110, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31980224

RESUMO

Staphylococcus aureus is one of the main pathogens found in cheeses produced with raw milk, including Minas artisanal cheese from Brazil. However, information about S. aureus isolated from artisanal cheeses and its sources of production in small-scale dairies is very limited. We aimed to characterize the virulence factors of S. aureus isolated from raw milk, endogenous starter culture, Minas artisanal cheese, and cheese handlers from the region of Campo das Vertentes, Minas Gerais, Brazil. We identified the staphylococcal isolates by MALDI-TOF mass spectrometry. We evaluated biofilm production on Congo red agar and polystyrene plates. We used PCR to detect icaA, icaB, icaC, sea, seb, sec, sed, see, tsst-1, agr, and mecA. We evaluated the expression of staphylococcal toxin genes in PCR-positive staphylococcal isolates using quantitative reverse-transcription PCR, and we evaluated the production of these toxins and their hemolytic activity in vitro. We also evaluated the antimicrobial resistance profile of the staphylococcal isolates. For statistical analysis, we used cluster analysis, χ2 tests, and correspondence tests. We analyzed 76 staphylococcal isolates. According to PCR, 18.42, 18.42, 2.63, and 77.63% were positive for sea, tsst-1, sec, and agr, respectively. We found low expression of staphylococcal toxin genes according to quantitative reverse-transcription PCR, and only 2 staphylococcal isolates produced toxic shock syndrome toxins. A total of 43 staphylococcal isolates (56.58%) had hemolytic activity; 53 were biofilm-forming on Congo red agar (69.73%), and 62 on polystyrene plates (81.58%). None of the staphylococcal isolates expressed the mecA gene, and none presented a multi-drug resistance pattern. The highest resistance was observed for penicillin G (67.11%) in 51 isolates and for tetracycline (27.63%) in 21 isolates. The staphylococcal isolates we evaluated had toxigenic potential, with a higher prevalence of sea and tsst-1. Biofilm production was the main virulence factor of the studied bacteria. Six clusters were formed whose distribution frequencies differed for hemolytic activity, biofilm formation (qualitative and quantitative analyses), and resistance to penicillin, tetracycline, and erythromycin. These findings emphasize the need for effective measures to prevent staphylococcal food poisoning by limiting S. aureus growth and enterotoxin formation throughout the food production chain and the final product.


Assuntos
Biofilmes/crescimento & desenvolvimento , Queijo/microbiologia , Farmacorresistência Bacteriana , Choque Séptico/microbiologia , Intoxicação Alimentar Estafilocócica/microbiologia , Staphylococcus aureus/genética , Fatores de Virulência , Animais , Antibacterianos/farmacologia , Toxinas Bacterianas/genética , Brasil , Enterotoxinas/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Superantígenos/genética
16.
Arch Gynecol Obstet ; 301(4): 869-874, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32200420

RESUMO

PURPOSE: We investigated whether pregnancy/birth anxiety is associated with shorter gestation while maternal chronic stress and depressive symptoms are associated with lower birth weight; we also examined whether experiencing daily uplifts prenatally may contribute to a more favorable birth outcome. METHODS: Thirty-four healthy second trimester pregnant women responded to questions regarding their experience of pregnancy/birth anxiety, chronic stress, depressive symptoms, and daily uplifts. Information on birth outcome was obtained from medical records. RESULTS: Maternal pregnancy/birth anxiety, depression, and stress were unrelated to birth outcomes. Daily uplifts were associated with gestational age at birth (B = 2.0, p = 0.01), neonatal weight (B = 46.9, p = 0.00), and size (B = 10.6, p = 0.01). Our results suggest that pregnancy/birth anxiety is not associated with shorter gestation as well as depression and stress seem to not predict lower birth weight. CONCLUSION: We expand the literature by showing that experiencing daily uplifts during mid-gestation may further fetal development.


Assuntos
Idade Gestacional , Segundo Trimestre da Gravidez/psicologia , Gestantes/psicologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Estudos Prospectivos
17.
HIV Med ; 20(10): 691-698, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31532902

RESUMO

OBJECTIVES: Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open-label trial comparing ritonavir-boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)-naïve HIV-positive adults. METHODS: A cross-sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. RESULTS: The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV-1 RNA load was 4.7 log10 HIV-1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/µL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV-1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/µL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. CONCLUSIONS: Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV , Telômero , Adulto , Idoso , Estudos Transversais , Darunavir/uso terapêutico , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Raltegravir Potássico/uso terapêutico , Ritonavir/uso terapêutico , Tenofovir/uso terapêutico
18.
Nanotechnology ; 30(5): 055301, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30521490

RESUMO

Metamaterials and metasurfaces provide unprecedented opportunities for designing light-matter interactions. Optical properties of hyperbolic metamaterials with meta-atoms based on plasmonic nanorods, important in nonlinear optics, sensing and spontaneous emission control, can be tuned by varying geometrical sizes and arrangement of the meta-atoms. At the same time the role of the shape of the meta-atoms forming the array has not been studied. We present the fabrication and optical characterization of metamaterials based on arrays of plasmonic nanocones closely packed at the subwavelength scale. The plasmonic mode structure of the individual nanocones and pronounced coupling effects between them provide multiple degrees of freedom to engineer both the field enhancement and the optical properties of the resulting metamaterials. The metamaterials are fabricated using a scalable manufacturing procedure, allowing mass-production at the centimeter scale. The ultra-sharp cone apex ([Formula: see text]2 nm) and the associated field enhancement provide an extremely high density of electromagnetic hot-spots (∼1010 cm-2). These properties of nanocone-based metamaterials are important for the development of gradient-index metamaterials and in numerous applications in fluorescence enhancement, surface enhanced Raman spectroscopy as well as hot-carrier plasmonics and photocatalysis.

19.
J Appl Microbiol ; 126(3): 796-810, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30472814

RESUMO

AIMS: To examine the antioxidant activity of Bacterioruberin (Bctr)-rich extracts isolated from a hyperpigmented, genetically modified Haloferax volcanii strain (HVLON3) and to investigate the effect on cold-sensitive ram sperm cells. METHODS AND RESULTS: The strain HVLON3 produces higher Bctr amounts than most haloarchaea (220 ± 13 mg g-1 DW). HVLON3-Bctr extract has higher antioxidant activity than ß-carotene (threefold) as evaluated using 2,2 diphenyl-1-picrylhydrazyl combined with Electron Paramagnetic Resonance analysis (EC50 4·5 × 10-5  mol l-1 vs 13·9 × 10-5  mol l-1 respectively). Different concentrations of HVLON3-Bctr extracts were assayed on ram sperm after freezing/thawing and physiologically relevant parameters were examined. Extracts containing 7 and 20 µmol l-1 Bctr significantly improved cell viability (P < 0·0001), total and progressive motility (P < 0·0001) and sperm velocities (P = 0·0172 for curvilinear velocity VCL, P = 0·0268 for average path velocity VAP and P = 0·0181 for straight line velocity VSL) and did not affect other parameters evaluated. CONCLUSIONS: HVLON3 is an excellent source of natural microbial C50 carotenoids with applicability in Biotechnology, Biomedical and Veterinary fields. HVLON3 Bctr extract improves the quality of cryopreserved ram sperm cells and could be applied to increase insemination yields. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an insight on the bioactive properties of a bioproduct derived from haloarchaea (carotenoids) which are so far underexploited.


Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Haloferax volcanii/química , Espermatozoides/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Carotenoides/metabolismo , Criopreservação , Haloferax volcanii/genética , Haloferax volcanii/metabolismo , Masculino , Ovinos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/citologia
20.
J Appl Microbiol ; 126(5): 1618-1630, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803104

RESUMO

AIMS: The purpose of this study was to apply cDNA approach for the characterization of active prokaryotic community to understand microbial scenarios and performance of an AnSBR digester fed with acid hydrolysates of Agave tequilana var. azul bagasse (ATAB). METHODS AND RESULTS: The digester was implemented for methane production under organic loading rate (OLR) disturbances to correlate physicochemical variables with changes in abundance, diversity and population dynamics of active Bacteria and Archaea by principal components analysis (PCA). Results indicated that methane yield increased as well as active syntrophic relationships for interspecies hydrogen/formate (Anaerolinaceae-Methanobacterium beijingense) and acetate (Anaerolinaceae-Methanosaeta concilii) transfers at 8 g-COD l-1  day-1 . However, methane yield was negatively affected at 16 g-COD l-1  day-1 due to the competition for acetate by active Desulfovibrio marrakechensis and volatile fatty acids inhibition. CONCLUSIONS: Microbial scenarios obtained by PCA correlations indicated that methane production from acid hydrolysates of ATAB was feasible at 8 g-COD l-1  day-1 . The digester operation at higher OLR only favoured methanogenesis by the hydrogenotrophic pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Only cDNA analysis showed Archaea population dynamics, exhibiting high correlation with physicochemical variables towards the understanding of the methanogenic digester performance during OLR disturbances.


Assuntos
Agave , Archaea/metabolismo , Bactérias/metabolismo , Reatores Biológicos/microbiologia , Metano , Agave/química , Agave/metabolismo , Metano/análise , Metano/metabolismo
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