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1.
BMJ Open ; 14(2): e079824, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38346874

RESUMEN

INTRODUCTION: A non-contrast CT head scan (NCCTH) is the most common cross-sectional imaging investigation requested in the emergency department. Advances in computer vision have led to development of several artificial intelligence (AI) tools to detect abnormalities on NCCTH. These tools are intended to provide clinical decision support for clinicians, rather than stand-alone diagnostic devices. However, validation studies mostly compare AI performance against radiologists, and there is relative paucity of evidence on the impact of AI assistance on other healthcare staff who review NCCTH in their daily clinical practice. METHODS AND ANALYSIS: A retrospective data set of 150 NCCTH will be compiled, to include 60 control cases and 90 cases with intracranial haemorrhage, hypodensities suggestive of infarct, midline shift, mass effect or skull fracture. The intracranial haemorrhage cases will be subclassified into extradural, subdural, subarachnoid, intraparenchymal and intraventricular. 30 readers will be recruited across four National Health Service (NHS) trusts including 10 general radiologists, 15 emergency medicine clinicians and 5 CT radiographers of varying experience. Readers will interpret each scan first without, then with, the assistance of the qER EU 2.0 AI tool, with an intervening 2-week washout period. Using a panel of neuroradiologists as ground truth, the stand-alone performance of qER will be assessed, and its impact on the readers' performance will be analysed as change in accuracy (area under the curve), median review time per scan and self-reported diagnostic confidence. Subgroup analyses will be performed by reader professional group, reader seniority, pathological finding, and neuroradiologist-rated difficulty. ETHICS AND DISSEMINATION: The study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved 13 December 2022). The use of anonymised retrospective NCCTH has been authorised by Oxford University Hospitals. The results will be presented at relevant conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06018545.


Asunto(s)
Inteligencia Artificial , Medicina Estatal , Humanos , Estudios Retrospectivos , Hemorragias Intracraneales/diagnóstico por imagen , Técnicos Medios en Salud
2.
J Foot Ankle Surg ; 62(5): 888-892, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37369276

RESUMEN

The posterior tibial tendon is a gliding tendon which courses around the medial malleolus and fails in posterior tibialis tendon dysfunction (PTTD) leading to a flat foot deformity. Distal tibial bone spurs have been identified as a secondary sign of PTTD although they have not been quantified in detail. The aim of this study was to assess the association of tendon dysfunction with the bony morphology of the tibial retro-malleolar groove. We performed a retrospective review of the clinical presentation, plain radiographs, and 103 magnetic resonance imaging (MRI) scans in 82 consecutive patients with PTTD compared with a non-PTTD group. We carried out a quantitative and qualitative assessment of the presence of plain radiographic bone spurs, stage of PTTD and MRI imaging of the morphology of the tibial bony malleolar groove. Plain radiographic bone spurs, as a secondary sign of PTTD, were present in 21.3% of ankle radiographs. MRI bone spurs were identified in 26/41 (63.4%) for all high-grade partial and complete tears and 7/41 (17.1%) for isolated complete tears compared with only 3.9% of the non-PTTD group. There was a significant association between the presence of bone spurs on MRI imaging and high-grade partial and complete tibialis posterior tears (p < .001; odds ratio of 4.98). Eleven of 103 (10.7%) of spurs were large and in 4/103 (3.9%) were substantial enough to create a tunnel-like hypertrophic groove not previously reported. There is variation in the bony structure of the malleolar groove in PTTD not observed in the non-PTTD group. Further investigation over time may elucidate whether the groove morphology may lead to mechanical attrition of the tibialis posterior tendon and contribute to failure of healing and progressive tendon degeneration.


Asunto(s)
Exostosis , Pie Plano , Osteofito , Disfunción del Tendón Tibial Posterior , Humanos , Osteofito/complicaciones , Osteofito/patología , Disfunción del Tendón Tibial Posterior/diagnóstico por imagen , Disfunción del Tendón Tibial Posterior/complicaciones , Pie , Tendones/patología , Pie Plano/diagnóstico , Exostosis/complicaciones
3.
Eur Radiol ; 33(3): 2096-2104, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36282308

RESUMEN

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management.


Asunto(s)
COVID-19 , Humanos , Radiografía Torácica/métodos , Reproducibilidad de los Resultados , Radiografía , Radiólogos , Estudios Retrospectivos
4.
Biosens Bioelectron ; 137: 161-170, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31096082

RESUMEN

We report on a wearable tear bioelectronic platform, integrating a microfluidic electrochemical detector into an eyeglasses nose-bridge pad, for non-invasive monitoring of key tear biomarkers. The alcohol-oxidase (AOx) biosensing fluidic system allowed real-time tear collection and direct alcohol measurements in stimulated tears, leading to the first wearable platform for tear alcohol monitoring. Placed outside the eye region this fully wearable tear-sensing platform addresses drawbacks of sensor systems involving direct contact with the eye as the contact lenses platform. Integrating the wireless electronic circuitry into the eyeglasses frame thus yielded a fully portable, convenient-to-use fashionable sensing device. The tear alcohol sensing concept was demonstrated for monitoring of alcohol intake in human subjects over multiple drinking courses, displaying good correlation to parallel BAC measurements. We also demonstrate for the first time the ability to monitor tear glucose outside the eye and the utility of wearable devices for monitoring vitamin nutrients in connection to enzymatic flow detector and rapid voltammetric scanning, respectively. These developments pave the way to build an effective eyeglasses system capable of chemical tear analysis.


Asunto(s)
Técnicas Biosensibles , Anteojos , Monitoreo Fisiológico , Lágrimas/química , Alcoholes/química , Alcoholes/aislamiento & purificación , Glucosa/química , Glucosa/aislamiento & purificación , Humanos , Vitaminas/química , Vitaminas/aislamiento & purificación , Dispositivos Electrónicos Vestibles
5.
Nat Biotechnol ; 37(4): 389-406, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30804534

RESUMEN

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.


Asunto(s)
Técnicas Biosensibles/instrumentación , Monitoreo Fisiológico/instrumentación , Dispositivos Electrónicos Vestibles , Técnicas Biosensibles/tendencias , Biotecnología , Líquidos Corporales/química , Sistemas de Computación , Humanos , Iontoforesis/instrumentación , Dispositivos Laboratorio en un Chip , Monitoreo Fisiológico/tendencias , Saliva/química , Sudor/química , Lágrimas/química , Dispositivos Electrónicos Vestibles/tendencias
6.
Cancers (Basel) ; 11(2)2019 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-30678055

RESUMEN

Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.

7.
Acc Chem Res ; 51(11): 2820-2828, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30398344

RESUMEN

In this Account, we detail recent progress in wearable bioelectronic devices and discuss the future challenges and prospects of on-body noninvasive bioelectronic systems. Bioelectronics is a fast-growing interdisciplinary research field that involves interfacing biomaterials with electronics, covering an array of biodevices, encompassing biofuel cells, biosensors, ingestibles, and implantables. In particular, enzyme-based bioelectronics, built on diverse biocatalytic reactions, offers distinct advantages and represents a centerpiece of wearable biodevices. Such wearable bioelectronic devices predominately rely on oxidoreductase enzymes and have already demonstrated considerable promise for on-body applications ranging from highly selective noninvasive biomarker monitoring to epidermal energy harvesting. These systems can thus greatly increase the analytical capability of wearable devices from the ubiquitous monitoring of mobility and vital signs, toward the noninvasive analysis of important chemical biomarkers. Wearable enzyme electrodes offer exciting opportunities to a variety of areas, spanning from healthcare, sport, to the environment or defense. These include real-time noninvasive detection of biomarkers in biofluids (such as sweat, saliva, interstitial fluid and tears), and the monitoring of environmental pollutants and security threats in the immediate surrounding of the wearer. Furthermore, the interface of enzymes with conducting flexible electrode materials can be exploited for developing biofuel cells, which rely on the bioelectrocatalytic oxidation of biological fuels, such as lactate or glucose, for energy harvesting applications. Crucial for such successful application of enzymatic bioelectronics is deep knowledge of enzyme electron-transfer kinetics, enzyme stability, and enzyme immobilization strategies. Such understanding is critical for establishing efficient electrical contacting between the redox enzymes and the conducting electrode supports, which is of fundamental interest for the development of robust and efficient bioelectronic platforms. Furthermore, stretchable and flexible bioelectronic platforms, with mechanical properties similar to those of biological tissues, are essential for handling the rigors of on-body operation. As such, special attention must be given to changes in the behavior of enzymes due to the uncontrolled conditions of on-body operation (including diverse outdoor activities and different biofluids), for maintaining the attractive performance that these bioelectronics devices display in controlled laboratory settings. Therefore, a focus of this Account is on interfacing biocatalytic layers onto wearable electronic devices for creating efficient and stable on-body electrochemical biosensors and biofuel cells. With proper attention to key challenges and by leveraging the advantages of biocatalysis, electrochemistry, and flexible electronics, wearable bioelectronic devices could have a tremendous impact on diverse biomedical, fitness, and defense fields.


Asunto(s)
Técnicas Biosensibles/métodos , Enzimas/metabolismo , Dispositivos Electrónicos Vestibles , Biomarcadores/análisis , Técnicas Biosensibles/instrumentación , Líquidos Corporales/metabolismo , Teléfono Celular , Contaminantes Ambientales/análisis , Enzimas/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Humanos , Oxidorreductasas/química , Oxidorreductasas/metabolismo
8.
Adv Sci (Weinh) ; 5(10): 1800880, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30356971

RESUMEN

The development of wearable biosensors for continuous noninvasive monitoring of target biomarkers is limited to assays of a single sampled biofluid. An example of simultaneous noninvasive sampling and analysis of two different biofluids using a single wearable epidermal platform is demonstrated here. The concept is successfully realized through sweat stimulation (via transdermal pilocarpine delivery) at an anode, alongside extraction of interstitial fluid (ISF) at a cathode. The system thus allows on-demand, controlled sampling of the two epidermal biofluids at the same time, at two physically separate locations (on the same flexible platform) containing different electrochemical biosensors for monitoring the corresponding biomarkers. Such a dual biofluid sampling and analysis concept is implemented using a cost-effective screen-printing technique with body-compliant temporary tattoo materials and conformal wireless readout circuits to enable real-time measurement of biomarkers in the sampled epidermal biofluids. The performance of the developed wearable device is demonstrated by measuring sweat-alcohol and ISF-glucose in human subjects consuming food and alcoholic drinks. The different compositions of sweat and ISF with good correlations of their chemical constituents to their blood levels make the developed platform extremely attractive for enhancing the power and scope of next-generation noninvasive epidermal biosensing systems.

9.
Psychol Health ; 33(7): 872-887, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29350063

RESUMEN

OBJECTIVE: While many people with Type 1 diabetes find it difficult to achieve recommended blood glucose levels, a minority do achieve good control. Our study was conceived by patient and public (PP) partners and sought to learn about experiences of people living with well-controlled diabetes. DESIGN: A collaboration between academic health psychologists and five PP partners with experience of diabetes, who were trained to conduct and analyse semi-structured interviews. Fifteen adults with well-controlled Type 1 diabetes were interviewed about the history of their diabetes and their current self-management practices. Interviews were subjected to inductive thematic analysis. RESULTS: Eight sub-themes were arranged into two overarching themes, 'facing up to diabetes' and 'balance leads to freedom'. Participants described a process of acceptance and mastery of diabetes, and talked about how they gained a deeper understanding of bodily processes through trial and error. CONCLUSION: Based on the experiences of people with well-controlled Type 1 diabetes, interventions for people with this condition should encourage acceptance of the diagnosis and increasing confidence to experiment with behaviours (trial and error) to encourage 'mastery' of self-management. The research collaboration described here is an example of best practice for future researchers wanting to actively engage PP partners.


Asunto(s)
Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/terapia , Autocuidado/psicología , Adaptación Psicológica , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Femenino , Humanos , Masculino , Investigación Cualitativa
10.
Talanta ; 177: 163-170, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29108571

RESUMEN

The growing recent interest in wearable and mobile technologies has led to increased research efforts toward development of non-invasive glucose monitoring platforms. Continuous glucose monitoring addresses the limitations of finger-stick blood testing and provides the opportunity for optimal therapeutic interventions. This article reviews recent advances and challenges toward the development of non-invasive epidermal electrochemical glucose sensing systems. Recent reports claim success in glucose monitoring in human subjects using skin-worn electrochemical sensors. Such epidermal electrochemical biosensors obviate the disadvantages of minimally-invasive subcutaneous glucose biosensors and offer promise for improved glycemic control. The ability of such systems to monitor glucose non-invasively offers an attractive route toward advancing the management of diabetes and achieving improved glycemic control. However, realizing the potential diagnostic impact of these new epidermal sensing strategies would require extensive efforts toward addressing key technological challenges and establishing a reliable correlation to gold standard blood glucose meters.


Asunto(s)
Automonitorización de la Glucosa Sanguínea/instrumentación , Epidermis/química , Dispositivos Electrónicos Vestibles , Electroquímica , Humanos
11.
Curr Opin Electrochem ; 10: 126-135, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30859141

RESUMEN

The rapid development of wearable sensing platforms in recent years has led to an array of viable monitoring applications for various target analytes. As a significant biomarker with high impact in diverse areas, the reliable on-body detection and continuous monitoring of alcohol has become a focus of many such systems. Currently, several commercial sensing platforms are available that are capable of transdermal monitoring of alcohol consumption using insensible sweat. Drawbacks of existing alcohol sensing platforms that apply this sensing strategy have led to efforts in developing wearable biosensors capable of real-time alcohol detection in sampled biofluids such as sensible sweat and skin interstitial fluid. This review discusses the current trends in wearable electrochemical alcohol biosensing and highlights recent advances in such systems toward continuous, real-time monitoring of alcohol consumption. Our perspective on this important field is given with an outlook on the future of wearable electrochemical alcohol biosensors.

12.
ACS Sens ; 2(12): 1860-1868, 2017 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-29152973

RESUMEN

Despite tremendous recent efforts, noninvasive sweat monitoring is still far from delivering its early analytical promise. Here, we describe a flexible epidermal microfluidic detection platform fabricated through hybridization of lithographic and screen-printed technologies, for efficient and fast sweat sampling and continuous, real-time electrochemical monitoring of glucose and lactate levels. This soft, skin-mounted device judiciously merges lab-on-a-chip and electrochemical detection technologies, integrated with a miniaturized flexible electronic board for real-time wireless data transmission to a mobile device. Modeling of the device design and sweat flow conditions allowed optimization of the sampling process and the microchannel layout for achieving attractive fluid dynamics and rapid filling of the detection reservoir (within 8 min from starting exercise). The wearable microdevice thus enabled efficient natural sweat pumping to the electrochemical detection chamber containing the enzyme-modified electrode transducers. The fabricated device can be easily mounted on the epidermis without hindrance to the wearer and displays resiliency against continuous mechanical deformation expected from such epidermal wear. Amperometric biosensing of lactate and glucose from the rapidly generated sweat, using the corresponding immobilized oxidase enzymes, was wirelessly monitored during cycling activity of different healthy subjects. This ability to monitor sweat glucose levels introduces new possibilities for effective diabetes management, while similar lactate monitoring paves the way for new wearable fitness applications. The new epidermal microfluidic electrochemical detection strategy represents an attractive alternative to recently reported colorimetric sweat-monitoring methods, and hence holds considerable promise for practical fitness or health monitoring applications.


Asunto(s)
Técnicas Biosensibles/instrumentación , Técnicas Electroquímicas/instrumentación , Glucosa/análisis , Ácido Láctico/análisis , Técnicas Analíticas Microfluídicas/instrumentación , Sudor/química , Técnicas Biosensibles/métodos , Dimetilpolisiloxanos/química , Técnicas Electroquímicas/métodos , Enzimas Inmovilizadas/química , Epidermis/metabolismo , Glucosa Oxidasa/química , Humanos , Dispositivos Laboratorio en un Chip , Límite de Detección , Técnicas Analíticas Microfluídicas/métodos , Oxigenasas de Función Mixta/química , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos
13.
ACS Sens ; 2(10): 1531-1538, 2017 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-29019246

RESUMEN

This work describes a wireless wearable ring-based multiplexed chemical sensor platform for rapid electrochemical monitoring of explosive and nerve-agent threats in vapor and liquid phases. The ring-based sensor system consists of two parts: a set of printed electrochemical sensors and a miniaturized electronic interface, based on a battery-powered stamp-size potentiostat, for signal processing and wireless transmission of data. A wide range of electrochemical capabilities have thus been fully integrated into a 3D printed compact ring structure, toward performing fast square-wave voltammetry and chronoamperometric analyses, along with interchangeable screen-printed sensing electrodes for the rapid detection of different chemical threats. High analytical performance is demonstrated despite the remarkable miniaturization and integration of the ring system. The attractive capabilities of the wearable sensor ring system have been demonstrated for sensitive and rapid voltammetric and amperometric monitoring of nitroaromatic and peroxide explosives, respectively, along with amperometric biosensing of organophosphate (OP) nerve agents. Such ability of the miniaturized wearable sensor ring platform to simultaneously detect multiple chemical threats in both liquid and vapor phases and alert the wearer of such hazards offers considerable promise for meeting the demands of diverse defense and security scenarios.


Asunto(s)
Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Sustancias para la Guerra Química/análisis , Sustancias Explosivas/análisis , Joyas , Humanos , Tecnología Inalámbrica
14.
Biomacromolecules ; 18(8): 2583-2593, 2017 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-28657716

RESUMEN

Antibacterial polymers are potentially powerful biocides that can destroy bacteria on contact. Debate in the literature has surrounded the mechanism of action of polymeric biocides and the propensity for bacteria to develop resistance to them. There has been particular interest in whether surfaces with covalently coupled polymeric biocides have the same mechanism of action and resistance profile as similar soluble polymeric biocides. We designed and synthesized a series of poly(quaternary ammonium) polymers, with tailorable molecular structures and architectures, to engineer their antibacterial specificity and their ability to delay the development of bacterial resistance. These linear poly(quaternary ammonium) homopolymers and block copolymers, generated using atom transfer radical polymerization, had structure-dependent antibacterial specificity toward Gram positive and negative bacterial species. When single block copolymers contained two polymer segments of differing antibacterial specificity, the polymer combined the specificities of its two components. Nanoparticulate human serum albumin-poly(quaternary ammonium) conjugates of these same polymers, synthesized via "grafting from" atom transfer radical polymerization, were strongly biocidal and also exhibited a marked decrease in the rate of bacterial resistance development relative to linear polymers. These protein-biocide conjugates mimicked the behavior of surface-presented polycationic biocides rather than their nonproteinaceous counterparts.


Asunto(s)
Antibacterianos , Bacterias/crecimiento & desarrollo , Polímeros , Compuestos de Amonio Cuaternario , Albúmina Sérica Humana , Adsorción , Antibacterianos/química , Antibacterianos/farmacología , Células HEK293 , Humanos , Polímeros/química , Polímeros/farmacología , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Albúmina Sérica Humana/química , Albúmina Sérica Humana/farmacología
15.
Biomacromolecules ; 18(2): 576-586, 2017 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-28081602

RESUMEN

The reduced immunogenicity and increased stability of protein-polymer conjugates has made their use in therapeutic applications particularly attractive. However, the physicochemical interactions between polymer and protein, as well as the effect of this interaction on protein activity and stability, are still not fully understood. In this work, polymer-based protein engineering was used to examine the role of polymer physicochemical properties on the activity and stability of the chymotrypsin-polymer conjugates and their degree of binding to intestinal mucin. Four different chymotrypsin-polymer conjugates, each with the same polymer density, were synthesized using "grafting-from" atom transfer radical polymerization. The influence of polymer charge on chymotrypsin-polymer conjugate mucin binding, bioactivity, and stability in stomach acid was determined. Cationic polymers covalently attached to chymotrypsin showed high mucin binding, while zwitterionic, uncharged, and anionic polymers showed no mucin binding. Cationic polymers also increased chymotrypsin activity from pH 6-8, while zwitterionic polymers had no effect, and uncharged and anionic polymers decreased enzyme activity. Lastly, cationic polymers decreased the tendency of chymotrypsin to structurally unfold at extremely low pH, while uncharged and anionic polymers induced unfolding more quickly. We hypothesized that when polymers are covalently attached to the surface of a protein, the degree to which those polymers interact with the protein surface is the predominant determinant of whether the polymer will stabilize or inactivate the protein. Preferential interactions between the polymer and the protein lead to removal of water from the surface of the protein, and this, we believe, inactivates the enzyme.


Asunto(s)
Quimotripsina/metabolismo , Ácido Gástrico/química , Mucinas/metabolismo , Polímeros/metabolismo , Adhesión Celular , Quimotripsina/química , Humanos , Mucinas/química , Polimerizacion , Polímeros/química , Unión Proteica , Ingeniería de Proteínas
16.
J Oncol Pharm Pract ; 23(7): 496-501, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27543094

RESUMEN

Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student's t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Linfoma/tratamiento farmacológico , Metotrexato/administración & dosificación , Anciano , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
17.
Biosens Bioelectron ; 86: 446-453, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27424262

RESUMEN

Enzymatic biofuel cells (EBFCs) are capable of generating electricity from physiologically present fuels making them promising power sources for the future of implantable devices. The potential application of such systems is limited, however, by inefficient current generation. Polymer-based protein engineering (PBPE) offers a unique method to tailor enzyme function through tunable modification of the enzyme surface with functional polymers. In this study, we report on the modification of glucose oxidase (GOX) with ferrocene-containing redox polymers to increase current generation efficiency in an enzyme-modified anode. Poly(N-(3-dimethyl(ferrocenyl)methylammonium bromide)propyl acrylamide) (pFcAc) was grown from covalently attached, water-soluble initiator molecules on the surface of GOX in a "grafting-from" approach using atom transfer radical polymerization (ATRP). The covalently-coupled ferrocene-containing polymers on the enzyme surface promoted the effective "wiring" of the GOX active site to an external electrode. The resulting GOX-pFcAc conjugates generated over an order of magnitude increase in current generation efficiency and a 4-fold increase in maximum EBFC power density (≈1.7µWcm(-2)) with similar open circuit voltage (0.27V) compared to native GOX when physically adsorbed onto paddle-shaped electrodes made up of electrospun polyacrylonitrile fibers coated with gold nanoparticles and multi-wall carbon nanotubes. The formation of electroactive enzyme-redox polymer conjugates using PBPE represents a powerful new tool for the improvement of mediated enzyme-based bioelectronics without the need for free redox mediators or anode/cathode compartmentalization.


Asunto(s)
Aspergillus niger/enzimología , Fuentes de Energía Bioeléctrica , Compuestos Ferrosos/química , Glucosa Oxidasa/química , Polímeros/química , Resinas Acrílicas/química , Fuentes de Energía Bioeléctrica/microbiología , Electricidad , Electrodos , Metalocenos , Oxidación-Reducción , Polimerizacion
18.
Emerg Med Int ; 2016: 1915895, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27119024

RESUMEN

The importance of early access to prehospital care has been demonstrated in many medical emergencies. This work aims to describe the potential time benefit of implementing a student Community First Responder scheme to support ambulance services in an inner-city setting in the United Kingdom. Twenty final and penultimate year medical students in the UK were trained in the "First Person on Scene" Business and Technology Education Council (BTEC) qualification. Over 12 months, they attended 89 emergency calls in an inner-city setting as Community First Responders (CFRs), alongside the West Midlands Ambulance Service, UK. At the end of this period, a qualitative survey investigated the perceived educational value of the scheme. The mean CFR response time across all calls was an average of 3 minutes and 8 seconds less than ambulance crew response times. The largest difference was to calls relating to falls (12 min). The difference varied throughout the day, peaking between 16:00 and 18:00. All questionnaire respondents stated that they felt more prepared in assessing and treating acutely unwell patients. In this paper, the authors present a symbiotic solution which has both reduced time to first on scene and provided training and experience in medical emergencies for senior medical students.

19.
ACS Appl Mater Interfaces ; 7(7): 4056-65, 2015 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-25643030

RESUMEN

Enzymatic biofuel cells (EBFCs) utilize enzymes to convert chemical energy present in renewable biofuels into electrical energy and have shown much promise in the continuous powering of implantable devices. Currently, however, EBFCs are greatly limited in terms of power and operational stability with a majority of reported improvements requiring the inclusion of potentially toxic and unstable electron transfer mediators or multicompartment systems separated by a semipermeable membrane resulting in complicated setups. We report on the development of a simple, membrane/mediator-free EBFC utilizing novel electrodes of graphene and single-wall carbon nanotube cogel. These cogel electrodes had large surface area (∼ 800 m(2) g(-1)) that enabled high enzyme loading, large porosity for unhindered glucose transport and moderate electrical conductivity (∼ 0.2 S cm(-1)) for efficient charge collection. Glucose oxidase and bilirubin oxidase were physically adsorbed onto these electrodes to form anodes and cathodes, respectively, and the EBFC produced power densities up to 0.19 mW cm(-2) that correlated to 0.65 mW mL(-1) or 140 mW g(-1) of GOX with an open circuit voltage of 0.61 V. Further, the electrodes were rejuvenated by a simple wash and reloading procedure. We postulate these porous and ultrahigh surface area electrodes will be useful for biosensing applications, and will allow reuse of EBFCs.


Asunto(s)
Biocombustibles/análisis , Glucosa Oxidasa/química , Grafito/química , Nanotubos de Carbono/química , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/química , Fuentes de Energía Bioeléctrica , Electricidad , Electrodos , Transporte de Electrón
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