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1.
Surg Endosc ; 36(1): 621-630, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33543349

RESUMO

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.


Assuntos
Coledocolitíase , Derivação Gástrica , Laparoscopia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/cirurgia , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Laparoscopia/métodos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Front Neurosci ; 15: 673120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34121998

RESUMO

Machine Learning methods are often adopted to infer useful biomarkers for the early diagnosis of many neurodegenerative diseases and, in general, of neuroanatomical ageing. Some of these methods estimate the subject age from morphological brain data, which is then indicated as "brain age". The difference between such a predicted brain age and the actual chronological age of a subject can be used as an indication of a pathological deviation from normal brain ageing. An important use of the brain age model as biomarker is the prediction of Alzheimer's disease (AD) from structural Magnetic Resonance Imaging (MRI). Many different machine learning approaches have been applied to this specific predictive task, some of which have achieved high accuracy at the expense of the descriptiveness of the model. This work investigates an appropriate combination of data science techniques and linear models to provide, at the same time, high accuracy and good descriptiveness. The proposed method is based on a data workflow that include typical data science methods, such as outliers detection, feature selection, linear regression, and logistic regression. In particular, a novel inductive bias is introduced in the regression model, which is aimed at improving the accuracy and the specificity of the classification task. The method is compared to other machine learning approaches for AD classification based on morphological brain data with and without the use of the brain age, including Support Vector Machines and Deep Neural Networks. This study adopts brain MRI scans of 1, 901 subjects which have been acquired from three repositories (ADNI, AIBL, and IXI). A predictive model based only on the proposed apparent brain age and the chronological age has an accuracy of 88% and 92%, respectively, for male and female subjects, in a repeated cross-validation analysis, thus achieving a comparable or superior performance than state of the art machine learning methods. The advantage of the proposed method is that it maintains the morphological semantics of the input space throughout the regression and classification tasks. The accurate predictive model is also highly descriptive and can be used to generate potentially useful insights on the predictions.

4.
Lupus ; 30(4): 549-553, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33596714

RESUMO

Jane Austen died 200 years ago at the age of 41 and authors have attributed her premature death to a wide variety of causes, which include Addison's disease and lymphoma.We have reviewed all of her available letters and extricated relevant medical information which reveal rheumatism, facial skin lesions, fever and marked fluctuation of these symptoms. The severity of these symptoms increased, leading to her death within a year.This range of clinical features fulfils the most recent classification criteria for systemic lupus erythematosus.


Assuntos
Exantema/diagnóstico , Dermatoses Faciais/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Medicina Narrativa/história , Adulto , Causas de Morte , Cor , Diagnóstico Diferencial , Progressão da Doença , Fadiga/diagnóstico , Feminino , Febre/diagnóstico , História do Século XVIII , História do Século XIX , Humanos , Remissão Espontânea , Doenças Reumáticas/diagnóstico
5.
Econ Lett ; 199: 109433, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32836579

RESUMO

Loss aversion is a foundational bias and is a natural choice for interventions encouraging compliance during COVID-19. We compare the effectiveness of loss and gain messages and find no difference in the intention to comply with guidance or lockdown beliefs.

6.
Sch Psychol ; 35(5): 285-298, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32955273

RESUMO

Two hundred ninety-four children from low-income families (58% White, 17% Latinx, 25% Black; 54% girls; Mage = 4.49 years old at study entry) were recruited from Head Start classrooms to participate in a randomized-controlled trial of the project Research-based, Developmentally Informed (REDI) preschool intervention and then followed longitudinally for 10 years through 9th grade. At study entry, parents reported on their children's exposure to adverse childhood experiences (ACEs). Youth reported on their feelings of social-emotional distress and school bonding after making the transition into middle school (7th grade) and high school (9th grade). Multilevel latent profile analyses revealed three profiles of adolescent distress and school bonding. Increased rates of ACEs in early childhood predicted membership in adolescent profiles characterized by heightened social-emotional distress and reduced levels of school bonding. The REDI intervention that focused on promoting early social-emotional and language skills in preschool moderated the impact of early ACEs on adolescent adjustment and promoted youth resilience, significantly buffering children from the negative impact of early ACEs on their levels of social-emotional distress and school bonding. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Experiências Adversas da Infância , Intervenção Educacional Precoce/métodos , Ajustamento Emocional , Angústia Psicológica , Resiliência Psicológica , Ajustamento Social , Adolescente , Desenvolvimento Infantil , Pré-Escolar , Emoções , Feminino , Humanos , Idioma , Análise de Classes Latentes , Estudos Longitudinais , Masculino , Apego ao Objeto , Instituições Acadêmicas
7.
J Abnorm Child Psychol ; 48(12): 1569-1580, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32930912

RESUMO

Growing up in poverty increases youth risk for developing aggressive behavior problems, which, in turn, are associated with a host of problematic outcomes, including school drop-out, substance use, mental health problems, and delinquency. In part, this may be due to exposure to adverse school contexts that create socialization influences supporting aggression. In the current study, 356 children from low-income families (58% White, 17% Latinx, 25% Black; 54% girls) were followed from preschool through seventh grade. Longitudinal data included measures of the school-level contexts experienced by study participants during their elementary and middle school years, including school levels of poverty (percentage of students receiving free or reduced-price lunch) and academic achievement (percentage of students scoring below the basic proficiency level on state achievement tests). Regression analyses suggested little impact of these school-level contexts on teacher or parent ratings of aggression in fifth grade, controlling for child baseline aggression and demographics. In contrast, school-level contexts had significant effects on child aggression in seventh grade with unique contributions by school-level achievement, controlling for child fifth grade aggression and elementary school contexts along with baseline covariates. These effects were robust across teacher and parent ratings. Findings are discussed in terms of understanding the school-based socialization of aggressive behavior and implications for educational policy and prevention programming.


Assuntos
Agressão/psicologia , Comportamento Problema/psicologia , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/psicologia , Sucesso Acadêmico , Adolescente , Criança , Pré-Escolar , Escolaridade , Família , Feminino , Humanos , Estudos Longitudinais , Masculino , Pennsylvania , Pobreza
8.
Antibiotics (Basel) ; 9(8)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784625

RESUMO

Unnecessary antibiotic prescribing contributes to Antimicrobial Resistance posing a major public health risk. Estimates suggest as many as half of antibiotics prescribed for respiratory infections may be unnecessary. We conducted a three-armed unblinded cluster randomized controlled trial (ISRCTN trial registry 83322985). Interventions were a commitment poster (CP) advocating safe antibiotic prescribing or a CP plus an antimicrobial stewardship message (AM) on telephone appointment booking lines, tested against a usual care control group. The primary outcome measure was antibiotic item dispensing rates per 1000 population adjusted for practice demographics. The outcome measures for post-hoc analysis were dispensing rates of antibiotics usually prescribed for upper respiratory tract infections and broad spectrum antibiotics. In total, 196 practice units were randomized to usual care (n = 60), CP (n = 66), and CP&AM (n = 70). There was no effect on the overall dispensing rates for either interventions compared to usual care (CP 5.673, 95%CI -9.768 to 21.113, p = 0.458; CP&AM, -12.575, 95%CI -30.726 to 5.576, p = 0.167). Secondary analysis, which included pooling the data into one model, showed a significant effect of the AM (-18.444, 95%CI -32.596 to -4.292, p = 0.012). Fewer penicillins and macrolides were prescribed in the CP&AM intervention compared to usual care (-12.996, 95% CI -34.585 to -4.913, p = 0.018). Commitment posters did not reduce antibiotic prescribing. An automated patient antimicrobial stewardship message showed effects and requires further testing.

9.
Inorg Chem ; 58(12): 7705-7714, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31145593

RESUMO

Ruddlesden-Popper (layered perovskite) phases are attracting significant interest because of their unique potential for many applications requiring mixed ionic and electronic conductivity. Here we report a new, previously undiscovered layered perovskite of composition, Ce xSr2- xMnO4 ( x = 0.1, 0.2, and 0.3). Furthermore, we demonstrate that this new system is suitable for solar thermochemical hydrogen production (STCH). Synchrotron radiation X-ray diffraction and transmission electron microscopy are performed to characterize this new system. Density functional theory calculations of phase stability and oxygen vacancy formation energy (1.76, 2.24, and 2.66 eV/O atom, respectively with increasing Ce content) reinforce the potential of this phase for STCH application. Experimental hydrogen production results show that this materials system produces 2-3 times more hydrogen than the benchmark STCH oxide ceria at a reduction temperature of 1400 °C and an oxidation temperature of 1000 °C.

10.
Psychol Health ; 34(8): 922-942, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30917673

RESUMO

Objectives: To compare the impact of appearance versus health-framed messages on engagement in a brief web-based risk screening and alcohol reduction intervention. Design: Randomised trial delivered via Drinkaware's website. Visitors were exposed to appearance (n = 51,588) or health-framed messages (n = 52,639) directing them towards an AUDIT-C risk screening questionnaire. Users completing this questionnaire were given feedback on their risk level and extended frame-congruent information. Outcomes: The primary outcome is completion of the AUDIT-C questionnaire. The secondary outcome is whether the participant accessed any of four further resources. Results: The appearance-framed message led to a small but significant increase in the number of users completing the AUDIT-C compared to the health-framed message (n = 3,537, 6.86% versus n = 3,355, 6.37%, p < 0.01). Conversely, following subsequent risk feedback, users exposed to extended health-framed information were more likely to access further resources (n = 1,146, 2.17% versus n = 942, 1.83%, p < 0.01). Conclusions: Physical appearance-framed messages increased the likelihood of engagement with an online alcohol screening and brief intervention tool, whereas health-framed messages increased the likelihood of accessing further resources. This highlights the potential for the use of multi-level approaches in alcohol reduction interventions.


Assuntos
Consumo de Bebidas Alcoólicas/prevenção & controle , Comunicação em Saúde/métodos , Internet , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Inquéritos e Questionários , Reino Unido/epidemiologia , Adulto Jovem
11.
Ear Hear ; 40(2): 345-357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29933259

RESUMO

OBJECTIVES: The aim of this study was to determine whether auditory streaming (segregation of incoming sounds into separate sound sources) and the ability to anticipate future auditory events are affected in tinnitus sufferers compared with nontinnitus controls with matched levels of hearing. It was hypothesized that tinnitus would result in abnormal electroencephalography responses to tone deviants and tone omissions compared to controls for frequencies near the pitch of tinnitus, and this should correspond with increased levels of cortical γ and θ oscillatory rhythms. DESIGN: Sixteen individuals with tinnitus (10 men and 6 women; age, 53.44; SD, 12.92 years) and 14 control participants (8 men and 6 women; age, 50.25; SD, 18.54 years) took part in the study. A modified version of the ABA streaming paradigm, with repeating triplet pattern of two frequencies (A and B) presented as A-B-A, was used to examine deviant-related prediction error. Omission-related prediction errors were examined using a modified version of a tone-omission paradigm. Regions of interest were frontocentral, left frontal, right frontal, and temporal lobes. RESULTS: A larger N1c waveform was elicited in the absence of any tone deviation within the left primary auditory cortex of tinnitus participants. No differences were present between groups for omissions. The only difference in oscillatory band activity between the two groups in this study was in response to tones 7 semitones different from tinnitus pitch, with significantly lower ß-2 band activity present for the tinnitus group, correlating most with activity within the right inferior occipital gyrus. CONCLUSIONS: The findings from this study imply that cortical-level auditory stream segregation is altered among individuals with tinnitus.


Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/fisiopatologia , Potenciais Evocados Auditivos/fisiologia , Zumbido/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Eletroencefalografia , Feminino , Lobo Frontal , Ritmo Gama/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Temporal/fisiopatologia , Ritmo Teta/fisiologia
12.
Trials ; 19(1): 513, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241564

RESUMO

BACKGROUND: A shortage of organs available for transplantation is causing loss of life. Increasing the number of individuals on the National Health Service (NHS) Organ Donor Register (ODR) is one way to address the shortage of organs. In Great Britain, new drivers registering for their driving licence are invited to join the ODR. A further 17 million drivers renew their road tax online each year, presenting an additional opportunity to prompt drivers to join the ODR. This trial explores the effect of adding persuasive messages to a prompt to join the ODR at the end of road tax payment transactions. METHODS: In this pragmatic, parallel group, quasi-randomised controlled trial, drivers renewing their road tax or registering for a driving licence were alternately allocated, using a JavaScript randomisation code embedded in the GOV.UK website, to view a control prompt inviting sign-ups to the ODR or the same prompt plus one of seven theoretically informed persuasive messages; (i) social norms alone, (ii) social norms plus the NHS ODR logo, (iii) social norms plus an image, (iv) loss frame, (v) gain frame, (vi) reciprocity and (vii) cognitive dissonance. The trial took place over a 4-week period in June 2013. The primary outcome measure was participants completing the online registration form (sign-ups). RESULTS: Altogether, 1,085,322 website users were included in the study. Further, 1171 more sign-ups were completed under the most effective message (reciprocity) compared to the control prompt alone (reciprocity: n = 4256, control: n = 3085; odds ratio, OR 1.38, 95% confidence interval 1.32-1.45, p < 0.001). The loss-framed message was as effective. All messages increased sign-ups compared to the control prompt apart from the social norms message plus image (n = 2879; OR 0.94, 95% confidence interval 0.89-0.99, p < 0.05). CONCLUSIONS: Short persuasive messages alongside a prompt can persuade more ODR sign-ups for individuals renewing their road tax than a prompt alone. The most effective message remains in place today. Since the trial in 2013, the same message has been implemented across 25 government end-of-transaction websites on GOV.UK, resulting in 529,000 new registrations to the ODR up to 31st October 2017.


Assuntos
Condução de Veículo , Conhecimentos, Atitudes e Prática em Saúde , Licenciamento , Comunicação Persuasiva , Medicina Estatal , Impostos , Doadores de Tecidos/psicologia , Obtenção de Tecidos e Órgãos , Cognição , Humanos , Opinião Pública , Sistema de Registros , Normas Sociais , Doadores de Tecidos/provisão & distribuição , Reino Unido
13.
J Sport Rehabil ; 27(3): 230-236, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28422559

RESUMO

CONTEXT: Foot and ankle injuries are common and often require a nonweight-bearing period of immobilization for the involved leg. This nonweight-bearing period usually results in muscle atrophy for the involved leg. There is a dearth of objective data describing muscle activation for different ambulatory aids that are used during the aforementioned nonweight-bearing period. OBJECTIVE: To compare activation amplitudes for 4 leg muscles during (1) able-bodied gait and (2) ambulation involving 3 different ambulatory aids that can be used during the acute phase of foot and ankle injury care. DESIGN: Within-subject, repeated measures. SETTING: University biomechanics laboratory. PARTICIPANTS: Sixteen able-bodied individuals (7 females and 9 males). INTERVENTION: Each participant performed able-bodied gait and ambulation using 3 different ambulatory aids (traditional axillary crutches, knee scooter, and a novel lower-leg prosthesis). MAIN OUTCOME MEASURE: Muscle activation amplitude quantified via mean surface electromyography amplitude throughout the stance phase of ambulation. RESULTS: Numerous statistical differences (P < .05) existed for muscle activation amplitude between the 4 observed muscles, 3 ambulatory aids, and able-bodied gait. For the involved leg, comparing the 3 ambulatory aids: (1) knee scooter ambulation resulted in the greatest vastus lateralis activation, (2) ambulation using the novel prosthesis and traditional crutches resulted in greater biceps femoris activation than knee scooter ambulation, and (3) ambulation using the novel prosthesis resulted in the greatest gastrocnemius activation (P < .05). Generally speaking, muscle activation amplitudes were most similar to able-bodied gait when subjects were ambulating using the knee scooter or novel prosthesis. CONCLUSIONS: Type of ambulatory aid influences muscle activation amplitude. Traditional axillary crutches appear to be less likely to mitigate muscle atrophy during the nonweighting, immobilization period that often follows foot or ankle injuries. Researchers and clinicians should consider these results when recommending ambulatory aids for foot or ankle injuries.


Assuntos
Marcha/fisiologia , Extremidade Inferior/fisiologia , Músculo Esquelético/fisiologia , Equipamentos Ortopédicos , Adolescente , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Caminhada/fisiologia , Adulto Jovem
14.
J Drug Target ; 25(9-10): 910-918, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28795867

RESUMO

Understanding how polymers interact with biological membranes is important for the development of polymer-based therapeutics and wider biomedical applications. Here, biophysical methods (surface pressure measurements, external reflection FTIR) have been used to investigate the interaction between PAMAM dendrimers (Generation 5 or 4.5) and anionic (DPPG) or zwitterionic (DPPC) model membranes. We observed a concentration-dependent binding behaviour of both PAMAM species to both model membranes; however, equivalent levels of penetration into DPPC monolayers required approximately 10-fold higher dendrimer concentrations than for penetration into DPPG monolayers. Overall, the anionic PAMAM G4.5 showed a slightly better penetration ability which could be caused by repulsive forces towards the lipid layers. In comparison, increasing concentration of cationic PAMAM G5 leads to saturation of adsorption at the anionic lipid surface before penetration into the lipid layer likely driven by electrostatic attraction. Our studies also showed that physiologically relevant concentrations of sodium chloride (144 mM) decreased PAMAM penetration into DPPG monolayers but did not significantly affect the dendrimer-DPPC interaction. These results provide an insight into the mechanism of interaction between charged dendritic polymers with a lipid interface and show that the nature of such interactions are affected by lipid headgroup, dendrimer charge and solution salinity.


Assuntos
Dendrímeros/química , Lipídeos/química , Membranas Artificiais , Nylons/química , Polímeros/química , Ânions , Fenômenos Biofísicos/fisiologia , Cátions , Dendrímeros/metabolismo , Nylons/metabolismo , Polímeros/metabolismo
15.
Int J Audiol ; 56(9): 706-710, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28485673

RESUMO

OBJECTIVE: To undertake a preliminary evaluation of the test-retest reliability, and accuracy of an iPad audiometer app using commercial earphones as a low-cost alternative to a clinical audiometer in a restricted sample of normal hearing participants. DESIGN: Twenty participants self-reporting normal hearing undertook four pure-tone audiometry tests in a single session. Two tests were performed with a 2-channel Type 1 audiometer (GSI-61) using EAR insert earphones and two tests with an iPad based app (Audiogram Mobile) using Apple earbud headphones. STUDY SAMPLE: Twenty normal hearing participants (13 female and seven male participants, aged 21-26 years) were recruited for the test-retest and accuracy evaluations. RESULTS: The app resulted in different thresholds to the audiometer (F(1, 19) = 16.635, p < 0.001). However test-retest reliability was similar. The app froze or quit unexpectedly over 25% of times used. CONCLUSIONS: Audiometer apps have great potential for clinical settings, especially in resource scarce environments, but reliability should not be assumed. While a low cost-alternative to standard transducers, issues of accuracy and calibration of consumer headphones need to be addressed before such combinations can be used with confidence.


Assuntos
Audiometria/instrumentação , Aplicativos Móveis , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
16.
Behav Sci (Basel) ; 7(2)2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28452941

RESUMO

We report results from a large online randomised tax experiment in Guatemala. The trial involves short messages and choices presented to taxpayers as part of a CAPTCHA pop-up window immediately before they file a tax return, with the aim of priming honest declarations. In total our sample includes 627,242 taxpayers and 3,232,430 tax declarations made over four months. Treatments include: honesty declaration; information about public goods; information about penalties for dishonesty, questions allowing a taxpayer to choose which public good they think tax money should be spent on; or questions allowing a taxpayer to state a view on the penalty for not declaring honestly. We find no impact of any of these treatments on the average amount of tax declared. We discuss potential causes for this null effect and implications for 'online nudges' around honesty priming.

17.
Langmuir ; 33(19): 4847-4853, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28448148

RESUMO

We have studied how puroindoline-b (PINB) mutants bind to model eukaryotic membranes dependent on binary composition of anionic:zwitterionic phospholipids and the presence of cholesterol and sphingomyelin in the model membrane. We have found that the trends in lipid binding behavior are different for wild-type PINB compared to its naturally occurring PINB(Trp44Arg) mutant form and have seen evidence of protein-induced domain formation within the lipid layer structure. Results show that selective binding of antimicrobial peptides to different membrane types is as a result of differences in lipid composition and the arrangement of lipids within the membrane surface. However, membrane-binding behavior is not easily predicted; it is determined by net charge, hydrophobicity, and the amphiphilicity of the protein/peptide lipid-binding domain.


Assuntos
Eucariotos , Sequência de Aminoácidos , Arginina , Bicamadas Lipídicas , Peptídeos , Fosfolipídeos , Triptofano
18.
Eur Biophys J ; 46(7): 655-663, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28116476

RESUMO

Membrane transporters are a vital class of proteins for which there is little available structural and thermodynamic information. The Major Facilitator Superfamily (MFS) is a large group of transport proteins responsible for transporting a wide range of substrates in eukaryotes and prokaryotes. We have used far-UV circular dichroism (CD) to assess whether transporters from this superfamily have the same chemical and thermal stability. We have compared the stability of five different MFS transporters; PepTSo from Shewanella oneidensis and LacY, GalP, GlpT and XylE from Escherichia coli, as well as a known stable mutant of LacY, LacY-C154G. CD stability measurements revealed that these transporters fall into two broad categories. The 'urea-sensitive' category includes LacY-WT, GalP and GlpT, which each lose around a third of their secondary structure in 8 M urea and two-thirds in the harsher denaturant guanidine hydrochloride (GuHCl). The 'urea-resistant' category includes LacY-C154G, XylE and PepTSo. These resistant transporters lose very little secondary structure in 8 M urea, and LacY-C154G and PepTSo resist denaturation by GuHCl up to a concentration of 4 M. The stabilities of LacY, GlpT, XylE and PepTSo correlated with their crystal structure conformations, implying that a similar conformation is adopted in vitro. The 'urea-sensitive' transporters LacY and GlpT were crystallised inward-open states, while XylE and PepTSo were crystallised in occluded states. This study highlights the importance of studying a wide range of similar proteins, as a similar secondary structure and overall function does not necessarily confer the same stability in vitro.


Assuntos
Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Guanidina/farmacologia , Ligantes , Modelos Moleculares , Domínios Proteicos , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína , Desdobramento de Proteína/efeitos dos fármacos , Ureia/farmacologia
19.
Lancet ; 387(10029): 1743-52, 2016 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-26898856

RESUMO

BACKGROUND: Unnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England. METHODS: In this randomised, 2 × 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed. FINDINGS: Between Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126.98 (95% CI 125.68-128.27) in the feedback intervention group and 131.25 (130.33-132.16) in the control group, a difference of 4.27 (3.3%; incidence rate ratio [IRR] 0.967 [95% CI 0.957-0.977]; p<0.0001), representing an estimated 73,406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient-focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135.00 [95% CI 133.77-136.22] in the patient-focused intervention group and 133.98 [133.06-134.90] in the control group; IRR for difference between groups 1.01, 95% CI 1.00-1.02; p=0.105). INTERPRETATION: Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes. FUNDING: Public Health England.


Assuntos
Antibacterianos/uso terapêutico , Feedback Formativo , Clínicos Gerais/educação , Prescrição Inadequada/prevenção & controle , Padrões de Prática Médica , Normas Sociais , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Langmuir ; 32(8): 2050-7, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26813886

RESUMO

The interaction between tryptophan-rich puroindoline proteins and model bacterial membranes at the air-liquid interface has been investigated by FTIR spectroscopy, surface pressure measurements, and Brewster angle microscopy. The role of different lipid constituents on the interactions between lipid membrane and protein was studied using wild type (Pin-b) and mutant (Trp44 to Arg44 mutant, Pin-bs) puroindoline proteins. The results show differences in the lipid selectivity of the two proteins in terms of preferential binding to specific lipid head groups in mixed lipid systems. Pin-b wild type was able to penetrate mixed layers of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) head groups more deeply compared to the mutant Pin-bs. Increasing saturation of the lipid tails increased penetration and adsorption of Pin-b wild type, but again the response of the mutant form differed. The results provide insight as to the role of membrane architecture, lipid composition, and fluidity on antimicrobial activity of proteins. Data show distinct differences in the lipid binding behavior of Pin-b as a result of a single residue mutation, highlighting the importance of hydrophobic and charged amino acids in antimicrobial protein and peptide activity.


Assuntos
Membrana Celular/química , Escherichia coli/química , Lipídeos de Membrana/química , Membranas Artificiais , Fosfatidiletanolaminas/química , Fosfatidilgliceróis/química , Proteínas de Plantas/química , Mutação , Proteínas de Plantas/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Triticum
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