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2.
Ear Nose Throat J ; 102(10): 629-631, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34121481

RESUMO

SIGNIFICANCE STATEMENT: Acute febrile neutrophilic dermatosis (Sweet syndrome) is a rare idiopathic condition characterized by fever and whole-body rash of tender erythematous plaques of unknown etiology. Otorhinolaryngologic manifestations of the disease can be severe, yet they are sparsely reported in the literature. We present the first documented case of laryngeal involvement of Sweet syndrome.


Assuntos
Laringe , Síndrome de Sweet , Humanos , Febre , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/etiologia
3.
AIDS Behav ; 26(11): 3597-3606, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35900708

RESUMO

A well-documented barrier to voluntary medical male circumcision (VMMC) is financial loss due to the missed opportunity to work while undergoing and recovering from VMMC. We implemented a 2-phased outcome evaluation to explore how enhanced demand creation and financial compensation equivalent to 3 days of missed work influence uptake of VMMC among men at high risk of HIV exposure in Zambia. In Phase 1, we implemented human-centered design-informed interpersonal communication. In Phase 2, financial compensation of ZMW 200 (~ US$17) was added. The proportion of men undergoing circumcision was significantly higher in Phase 2 compared to Phase 1 (38% vs 3%). The cost of demand creation and compensation per client circumcised was $151.54 in Phase 1 and $34.93 in Phase 2. Financial compensation is a cost-effective strategy for increasing VMMC uptake among high-risk men in Zambia, and VMMC programs may consider similar interventions suited to their context.


Assuntos
Circuncisão Masculina , Infecções por HIV , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Programas Voluntários , Zâmbia/epidemiologia
4.
Occup Med (Lond) ; 72(4): 264-272, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35363314

RESUMO

BACKGROUND: Hand dermatitis is a well-established occupational risk in nursing staff. AIMS: To explore skin health in nursing staff and to develop resources and recommendations to promote good skincare at work. METHODS: Cross-sectional survey. RESULTS: We analysed data from 1,545 surveys. Forty-six percent reported 'poor' skin health and the majority (93%) experienced at least one skin problem over the previous 12 months, with only 22% seeking help from their employer. Only 2% took time off work due to skin problems, with many expressing concerns that taking sick leave would be viewed negatively by others. Over half (53%) had reduced or stopped using antibacterial rubs and soap, and 18% had reduced the use of gloves. Most respondents used hand cream and over half used products they had purchased themselves. Only 42% received skin health care information from employers, with fewer (26%) receiving training on how to identify early signs of skin disease. Only 16% had access to skin surveillance in line with regulatory requirements. Only 26% of respondents were aware of the support offered by their professional nursing association. Suggestions for improving skin health included increasing publicity concerning the importance of skin health in healthcare settings, improving access to hand creams, better quality products, enhanced education and training and more involvement from Occupational Health (OH). CONCLUSIONS: Results confirm that poor skin health remains a persistent problem for nurses. Employers could do more to promote skin health and nurses need to be made more aware of the support and guidance offered by professional bodies.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem , Saúde Ocupacional , Estudos Transversais , Humanos , Pele , Inquéritos e Questionários
5.
Gynecol Oncol ; 164(3): 473-480, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35000796

RESUMO

Equality, equity, and parity in the workplace are necessary to optimize patient care across all aspects of medicine. Gender-based inequities remain an obstacle to quality of care, including within the now majority women subspecialty of gynecologic oncology. The results of the 2020 SGO State of the Society Survey prompted this evidence-based review. Evidence related to relevant aspects of the clinical care model by which women with malignancies are cared for is summarized. Recommendations are made that include ways to create work environments where all members of a gynecologic oncology clinical care team, regardless of gender, can thrive. These recommendations aim to improve equality and equity within the specialty and, in doing so, elevate the care that our patients receive.


Assuntos
Neoplasias dos Genitais Femininos , Local de Trabalho , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Masculino , Inquéritos e Questionários
6.
Sci Adv ; 6(45)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33158860

RESUMO

Arthropod herbivores cause substantial economic costs that drive an increasing need to develop environmentally sustainable approaches to herbivore control. Increasing plant diversity is expected to limit herbivory by altering plant-herbivore and predator-herbivore interactions, but the simultaneous influence of these interactions on herbivore impacts remains unexplored. We compiled 487 arthropod food webs in two long-running grassland biodiversity experiments in Europe and North America to investigate whether and how increasing plant diversity can reduce the impacts of herbivores on plants. We show that plants lose just under half as much energy to arthropod herbivores when in high-diversity mixtures versus monocultures and reveal that plant diversity decreases effects of herbivores on plants by simultaneously benefiting predators and reducing average herbivore food quality. These findings demonstrate that conserving plant diversity is crucial for maintaining interactions in food webs that provide natural control of herbivore pests.


Assuntos
Artrópodes , Herbivoria , Animais , Biodiversidade , Cadeia Alimentar , Plantas
7.
Phys Rev Lett ; 124(6): 063601, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32109106

RESUMO

We report on the realization of long-range Ising interactions in a cold gas of cesium atoms by Rydberg dressing. The interactions are enhanced by coupling to Rydberg states in the vicinity of a Förster resonance. We characterize the interactions by measuring the mean-field shift of the clock transition via Ramsey spectroscopy, observing one-axis twisting dynamics. We furthermore emulate a transverse-field Ising model by periodic application of a microwave field and detect dynamical signatures of the paramagnetic-ferromagnetic phase transition. Our results highlight the power of optical addressing for achieving local and dynamical control of interactions, enabling prospects ranging from investigating Floquet quantum criticality to producing tunable-range spin squeezing.

8.
Am J Infect Control ; 48(5): 503-506, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31924389

RESUMO

BACKGROUND: Alcohol based hand rubs (ABHR) are extremely effective at reducing microbial contamination and have an essential role in best practice hand hygiene described by the World Health Organization. METHODS: We determined ABHR drying time when performing hand hygiene in a laboratory setting. Which was followed by identifying the amount of ABHR needed for complete hand coverage. When the aforementioned was analyzed real-time data were gathered to examine the amount used for hand hygiene in a hospital setting. In parallel hands of healthcare workers (HCWs) were monitored for drying time and perception on ABHR use. RESULTS: In 86% (24,446,397/28,280,383) of the events a single dose of ABHR was used on clinical wards. Twenty-four HCWs expected hand hygiene to take 7.5 seconds (median; range 3-30 seconds). Forty-three HCWs show that 1.5 mL ABHR dose achieves the desired drying time according to World Health Organization guidelines (av. median 26 seconds), but is consistently perceived to have a longer drying time than expected (av. median 18 seconds). In-vivo results (n = 10) indicate that 2.25 mL ABHR is required for adequate coverage (82%-90%) of both sides of the hand. CONCLUSIONS: Results indicate that set standards for the use of ABHR do not match "in-vivo" behaviour of HCWs. Perceived drying times are shorter than actual drying time. The needed drying time to reach acceptable antimicrobial efficacy of ABHRs should be revisited.


Assuntos
Desinfecção das Mãos/métodos , Higienizadores de Mão/administração & dosagem , Fatores de Tempo , Infecção Hospitalar/prevenção & controle , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Fidelidade a Diretrizes , Mãos/microbiologia , Desinfecção das Mãos/normas , Higienizadores de Mão/química , Humanos , Resultado do Tratamento
9.
ISA Trans ; 95: 358-371, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31171304

RESUMO

The safety and public health during nuclear power plant operation can be enhanced by accurately recognizing and diagnosing potential problems when a malfunction occurs. However, there are still obvious technological gaps in fault diagnosis applications, mainly because adopting a single fault diagnosis method may reduce fault diagnosis accuracy. In addition, some of the proposed solutions rely heavily on fault examples, which cannot fully cover future possible fault modes in nuclear plant operation. This paper presents the results of a research in hybrid fault diagnosis techniques that utilizes support vector machine (SVM) and improved particle swarm optimization (PSO) to perform further diagnosis on the basis of qualitative reasoning by knowledge-based preliminary diagnosis and sample data provided by an on-line simulation model. Further, SVM has relatively good classification ability with small samples compared to other machine learning methodologies. However, there are some challenges in the selection of hyper-parameters in SVM that warrants the adoption of intelligent optimization algorithms. Hence, the major contribution of this paper is to propose a hybrid fault diagnosis method with a comprehensive and reasonable design. Also, improved PSO combined with a variety of search strategies are achieved and compared with other current optimization algorithms. Simulation tests are used to verify the accuracy and interpretability of research findings presented in this paper, which would be beneficial for intelligent execution of nuclear power plant operation.


Assuntos
Análise de Falha de Equipamento , Centrais Nucleares , Material Particulado , Máquina de Vetores de Suporte , Algoritmos , Simulação por Computador , Sistemas On-Line
10.
Bone Joint J ; 101-B(6_Supple_B): 104-109, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146563

RESUMO

AIMS: Tranexamic acid (TXA) has been shown to significantly reduce transfusion rates in primary total hip arthroplasties (THAs), but high-quality evidence is limited in the revision setting. The purpose of the current study was to compare the rate of blood transfusions and symptomatic venous thromboembolic events (VTEs) in a large cohort of revision THAs treated with or without intravenous (IV) TXA. PATIENTS AND METHODS: We performed a retrospective review of 3264 revision THAs (2645 patients) between 2005 and 2014, of which 1142 procedures received IV TXA (1 g at incision and 1 g at closure). The mean age in the revision group with TXA was 65 years (28 to 95), with 579 female patients (51%). The mean age in the revision group treated without TXA was 67 years (21 to 98), with 1160 female patients (55%). Outcomes analyzed included rates of transfusion and symptomatic VTEs between procedures undertaken with and without TXA. These comparisons were performed for the overall cohort, as well as within cases subcategorized for aseptic or septic aetiologies. A propensity score was developed to minimize bias between groups and utilized age at revision THA, sex, body mass index, American Society of Anesthesiologists (ASA) score, preoperative anticoagulation, and year of surgery. RESULTS: Tranexamic acid significantly and substantially reduced the rate of blood transfusions after revision THA overall from 54% to 26% (p < 0.001; adjusted relative risk (RR) 1.6; 95% confidence interval (CI) 1.3 to 1.9), with a significant reduction in both aseptic (49% to 18%; p < 0.001) and septic (73% to 53%; p = 0.04) revisions. The rate of VTE was minimal overall, with three events (0.3%) in the TXA group and four events (0.2%) in the non-TXA group. There were no significant differences in VTE rates based on TXA use or aetiology of revision. CONCLUSION: Intravenous TXA significantly reduced transfusion rates during all-cause revision THAs, including a subgroup analysis of both aseptic and septic cohorts. Adjusted risk using propensity modelling showed no statistical difference in rates of VTEs between either group. Cite this article: Bone Joint J 2019;100-B(6 Supple B):104-109.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Ácido Tranexâmico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/induzido quimicamente , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento , Trombose Venosa/induzido quimicamente , Adulto Jovem
11.
Br J Surg ; 105(5): 587-596, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29512137

RESUMO

BACKGROUND: Centralizing specialist cancer surgery services aims to reduce variations in quality of care and improve patient outcomes, but increases travel demands on patients and families. This study aimed to evaluate preferences of patients, health professionals and members of the public for the characteristics associated with centralization. METHODS: A discrete-choice experiment was conducted, using paper and electronic surveys. Participants comprised: former and current patients (at any stage of treatment) with prostate, bladder, kidney or oesophagogastric cancer who previously participated in the National Cancer Patient Experience Survey; health professionals with experience of cancer care (11 types including surgeons, nurses and oncologists); and members of the public. Choice scenarios were based on the following attributes: travel time to hospital, risk of serious complications, risk of death, annual number of operations at the centre, access to a specialist multidisciplinary team (MDT) and specialist surgeon cover after surgery. RESULTS: Responses were obtained from 444 individuals (206 patients, 111 health professionals and 127 members of the public). The response rate was 52·8 per cent for the patient sample; it was unknown for the other groups as the survey was distributed via multiple overlapping methods. Preferences were particularly influenced by risk of complications, risk of death and access to a specialist MDT. Participants were willing to travel, on average, 75 min longer in order to reduce their risk of complications by 1 per cent, and over 5 h longer to reduce risk of death by 1 per cent. Findings were similar across groups. CONCLUSION: Respondents' preferences in this selected sample were consistent with centralization.


Assuntos
Comportamento de Escolha , Neoplasias/cirurgia , Preferência do Paciente , Especialização/normas , Oncologia Cirúrgica/normas , Inquéritos e Questionários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
J Hosp Infect ; 98(4): 359-364, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28974469

RESUMO

BACKGROUND: Hand rubs containing alcohols such as isopropanol (IPA) or ethanol (EtOH) are widely used for hygienic hand disinfection, and are presented in different formats (i.e. liquid, gel or foam). AIM: To determine if there is any difference in efficacy between these two active ingredients in the three formats. In addition, an assessment of the drying time was undertaken. Two non-commercial, 'standard' formulations were tested in each format: one containing 60% IPA, and the other containing 80% EtOH. METHODS: EN 1500 tests were performed with 20 volunteers to assess efficacy. The reference product was 2 x 3 mL of 60% IPA for 60 s, as described in EN 1500 (2013). The test products were 3 mL of liquid, gel or foam format; one full EN 1500 test was performed for each formulation (60% IPA and 80% EtOH). To assess drying time, two different volumes (1.5 and 3.0 mL) of the test formulations in liquid, gel or foam format were applied to the hands of 15 volunteers. Volunteers self-reported when their hands were dry; at the end of the test, the volunteers were asked to rate the time taken to dry on a three-point scale (too short, OK, too long). FINDINGS: This study found no difference in antibacterial efficacy attributable to formulation or format for the two 'standard' ABHR formulations, as assessed by EN 1500. When measured objectively, the EtOH-based formulations dried more rapidly than the IPA-based formulations, and for both formulations, gels took longer to dry than other formats. User perception of drying time broadly agreed with objective measurement. CONCLUSION: Given that there was no difference in efficacy and only moderate difference in drying time, it is proposed that ABHR in liquid, foam or gel format may be appropriate, provided that the specific product passes the required efficacy and safety standards.


Assuntos
2-Propanol/farmacologia , Desinfetantes/farmacologia , Etanol/farmacologia , Géis/administração & dosagem , Desinfecção das Mãos/métodos , Mãos/microbiologia , Dessecação , Humanos , Fatores de Tempo , Resultado do Tratamento , Voluntários
13.
J Hosp Infect ; 95(2): 175-182, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28153555

RESUMO

BACKGROUND: Manufacturers' recommended dosages for alcohol-based hand rubs are typically determined by measuring product efficacy using a model protocol such as EN 1500; however, anecdotal reports and informal observation suggests that in many cases users self-titrate to much lower doses in real-world application. AIM: To examine the interdependence of alcohol-based hand-rub volume on in-vivo efficacy using the EN 1500 standard test method, on drying time on users' hands, and on their perceptions of acceptability. METHODS: Three formulations were studied using EN 1500 and a modification of this method. The modification used volumes ranging from 0.5 to 3.0 mL and 30 s application. Drying times were recorded and user acceptability was established using a three-point scale (too long, OK, or too short). Dying times were analysed in relation to hand surface area. FINDINGS: The drying time for all three products increased as a function of volume. The drying time displayed a positive association with volume and a negative association with hand surface area. The optimum volume for user acceptability was between 1.5 and 2 mL, yielding a drying time of between 20 and 30 s. CONCLUSION: Whereas EN 1500 is appropriate for establishing the efficacy of a hygienic hand-rub formulation compared to a benchmark, it does not reflect actual in-use conditions or the likely clinical effectiveness of the product. In particular, it fails to address the need to optimize the volume of application and user acceptability of the product.


Assuntos
Álcoois/administração & dosagem , Desinfetantes/administração & dosagem , Desinfecção das Mãos/métodos , Dessecação , Feminino , Humanos , Masculino , Fatores de Tempo , Voluntários
14.
J Eur Acad Dermatol Venereol ; 31(1): 53-64, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27545662

RESUMO

Contact dermatitis is one of the most common occupational diseases, with serious impact on quality of life, lost days at work and a condition that may be chronically relapsing. Regular prophylactic skin cream application is widely acknowledged to be an effective prevention strategy against occupational contact dermatitis; however, compliance rates remain low. To present a simple programme for skin cream application in the workplace with focus on implementation to drive down the rate of occupational irritant contact dermatitis, an expert panel of eight international dermatologists combined personal experience with extensive literature review. The recommendations are based on clinical experience as supported by evidence-based data from interventional studies. The authors identified three moments for skin cream application in the work place: (i) before starting a work period; (ii) after washing hands; and (iii) after work. Affecting behaviour change requires systematic communications, monitoring and reporting, which is proposed through Kotter's principles of organizational change management. Measurement tools are provided in the appendix. Interventional data based on application of this proposal is required to demonstrate its effectiveness.


Assuntos
Dermatite Irritante/prevenção & controle , Irritantes/toxicidade , Creme para a Pele/administração & dosagem , Local de Trabalho , Medicina Baseada em Evidências , Humanos
16.
Acta Chromatogr ; 28(3): 373-385, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27974871

RESUMO

Prions of the baker's yeast Saccharomyces cerevisiae allow for the inheritance of complex traits based solely on the acquisition of cytoplasmic protein aggregates and confer distinctive phenotypes to the cells which harbor them, creating heterogeneity within an otherwise clonal cell population. These phenotypes typically arise from a loss-of-function of the prion-forming protein that is unable to perform its normal cellular function(s) while sequestered in prion amyloid aggregates, but the specific biochemical consequences of prion infection are poorly understood. To begin to address this issue, we initiated a direct investigation into the potential control that yeast prions exert over fungal lipid content by utilizing the prions [URE3] and [PSI+], the first two prions discovered in yeast. We utilized silica gel high-performance thin-layer chromatography (HPTLC)-densitometry to conduct pair-wise quantifications of the relative levels of free sterols, free fatty acids, and triacylglycerols [petroleum ether-diethyl ether-acetic acid (80:20:1) mobile phase, phosphomolybdic acid (PMA) detection reagent]; steryl esters and squalene (hexane-petroleum ether-diethyl ether-acetic acid (50:20;5:1), PMA]; and phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol (chloroform-diethyl ether-acetic acid (65:25:4.5), cupric sulfate-phosphoric acid) in otherwise clonal prion-infected ([PSI+] or [URE3]) and prion-free ([psi-] or [ure-o]) cells in two growth phases: log-phase and stationary phase. Our analysis revealed multiple statistically significant differences (p < 0.00625) between prion-infected and prion-free cells. Interestingly, prion-induced changes varied dramatically by growth phase, indicating that prions exert differential influences on cell physiology between log and stationary growth. Further experimental replication and extension of the analysis to other prions is expected to resolve additional physiological effects of prion infection. This investigation demonstrates that HPTLC-densitometry is an effective method for studying prion-induced alterations in lipid content in yeast.

17.
Neurogastroenterol Motil ; 28(7): 1114-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26914765

RESUMO

BACKGROUND: Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of (12) Carbon ((12) C, regular) mannitol in food or from other sources may interfere with the test's interpretation. (13) Carbon ((13) C) constitutes 1% of carbon in nature and (13) C mannitol is a stable isotope. Our aim was to determine the performance of (13) C mannitol for measurement of intestinal permeability. METHODS: Ten healthy volunteers underwent intestinal permeability assay using coadministered (12) C mannitol, (13) C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography-mass spectrometry. KEY RESULTS: We found that (13) C mannitol can be distinguishable from (12) C mannitol on tandem mass spectrometry. In addition, (13) C mannitol had ~20-fold lower baseline contamination compared to (12) C mannitol. We describe here the (13) C mannitol assay method for the measurement of intestinal permeability. CONCLUSIONS & INFERENCES: In conclusion, (13) C mannitol is superior to (12) C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period.


Assuntos
Isótopos de Carbono/metabolismo , Isótopos de Carbono/urina , Absorção Intestinal/fisiologia , Manitol/metabolismo , Manitol/urina , Biomarcadores/metabolismo , Biomarcadores/urina , Isótopos de Carbono/administração & dosagem , Humanos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos
18.
Bioorg Med Chem ; 23(17): 5702-8, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26220520

RESUMO

The T box riboswitch is an intriguing potential target for antibacterial drug discovery. Found primarily in Gram-positive bacteria, the riboswitch regulates gene expression by selectively responding to uncharged tRNA to control transcription readthrough. Polyamines and molecular crowding are known to specifically affect RNA function, but their effect on T box riboswitch efficacy and tRNA affinity have not been fully characterized. A fluorescence-monitored in vitro transcription assay was developed to readily quantify these molecular interactions and to provide a moderate-throughput functional assay for a comprehensive drug discovery screening cascade. The polyamine spermidine specifically enhanced T box riboswitch readthrough efficacy with an EC50 = 0.58 mM independent of tRNA binding. Molecular crowding, simulated by the addition of polyethylene glycol, had no effect on tRNA affinity for the riboswitch, but did reduce the efficacy of tRNA-induced readthrough. These results indicate that the T box riboswitch tRNA affinity and readthrough efficacy are intricately modulated by environmental factors.


Assuntos
RNA de Transferência/metabolismo , Espermidina/química , Descoberta de Drogas , Modelos Moleculares
19.
Methods Enzymol ; 550: 363-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25605395

RESUMO

Riboswitches and other noncoding regulatory RNA are intriguing targets for the development of therapeutic agents. A significant challenge in the drug discovery process, however, is the identification of potent compounds that bind the target RNA specifically and disrupt its function. Essential to this process is an effectively designed cascade of screening assays. A screening cascade for identifying compounds that target the T box riboswitch antiterminator element is described. In the primary assays, moderate to higher throughput screening of compound libraries is achieved by combining the sensitivity of fluorescence techniques with functionally relevant assays. Active compounds are then validated and the binding to target RNA further characterized in secondary assays. The cascade of assays monitor ligand-induced changes in the steady-state fluorescence of an attached dye or internally incorporated 2-aminopurine; the fluorescence anisotropy of an RNA complex; and, the thermal denaturation fluorescence profile of a fluorophore-quencher labeled RNA. While the assays described have been developed for T box riboswitch-targeted drug discovery, the fluorescence methods and screening cascade design principles can be applied to drug discovery efforts targeted toward other medicinally relevant noncoding RNA.


Assuntos
Riboswitch/genética , Descoberta de Drogas , Polarização de Fluorescência
20.
Methods Mol Biol ; 1240: 135-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25352142

RESUMO

Changes in electrophoretic mobility upon complex formation with RNA can be used to probe structure-function relationships that are critical for complex formation. Here, we describe the application of this technique to monitor tRNA binding to the T box riboswitch antiterminator RNA.


Assuntos
Ensaio de Desvio de Mobilidade Eletroforética/métodos , RNA Bacteriano/metabolismo , RNA de Transferência/metabolismo , Riboswitch , Regiões Terminadoras Genéticas , Autorradiografia , Bacillus subtilis/metabolismo , Sequência de Bases , Dados de Sequência Molecular , RNA Bacteriano/genética , RNA de Transferência/genética , Soluções , Coloração e Rotulagem
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