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1.
EES Catal ; 2(1): 379-388, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38222063

RESUMO

Electrochemical CO2 reduction is a topic of major interest in contemporary research as an approach to use renewably-derived electricity to synthesise useful hydrocarbons from waste CO2. Various strategies have been developed to optimise this challenging reaction at electrode interfaces, but to-date, decoupled electrolysis has not been demonstrated for the reduction of CO2. Decoupled electrolysis aims to use electrochemically-derived charged redox mediators - electrical charge and potential vectors - to separate catalytic product formation from the electrode surface. Utilising an electrochemically generated highly reducing redox mediator; chromium propanediamine tetraacetate, we report the first successful application of decoupled electrolysis to electrochemical CO2 reduction. A study of metals and metal composites found formate to be the most accessible product, with bismuth metal giving the highest selectivity. Copper, tin, gold, nickel and molybdenum carbide heterogeneous catalysts were also investigated, in which cases H2 was found to be the major product, with minor yields of two-electron CO2 reduction products. Subsequent optimisation of the bismuth catalyst achieved a high formate selectivity of 85%. This method represents a radical new approach to CO2 electrolysis, which may be coupled directly with renewable energy storage technology and green electricity.

2.
ACS Appl Mater Interfaces ; 15(37): 43880-43886, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37671912

RESUMO

Formic acid (FA) is an important C1-containing feedstock that serves as a masked source of dihydrogen gas (H2). To encourage the adoption of cleaner (noncarbonaceous) energy sources, FA detection and sensing is thus of considerable interest. Here, we examine the use of a commercially available dye, azomethine-H (Az-H), for FA sensing. Solution studies confirm that FA quenches both the absorbance and the luminescence properties of Az-H. FA was additionally found to attenuate a known Az-H (E)-to-(Z) conformational change, suggesting an Az-H/FA interaction, possibly through hydrogen bonding; this phenomenon was probed using 1H NMR spectroscopy. Moving toward a solid-state sensor, the Az-H probe was incorporated into a gelatin-based matrix. On exposure to FA, the luminescence of this system was found to increase in a FA-dependent manner, attributed to the formation of stable hydrogen-bonded structures, facilitating a (Z)-to-(E) isomerization via imine protonation, allowing for production of the more luminescent (E)-isomer. This fluorogenic signal was used as a FA sensor with an estimated detection limit of ca. 0.4 ppb FA vapor. This work constitutes an important step toward a highly sensitive FA sensor in both the solution and solid state, opening new space for the detection of organic acids in differing chemical environments.

3.
Postgrad Med J ; 99(1171): 484-491, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37294723

RESUMO

Medical students have an essential role in medical research, yet often lack opportunities for involvement within randomised trials. This study aimed to understand the educational impact of clinical trial recruitment for medical students. Tracking wound infection with smartphone technology (TWIST) was a randomised controlled trial that included adult patients undergoing emergency abdominal surgery across two university teaching hospitals. All recruiters underwent prerecruitment training based on 'Generating Student Recruiters for Randomised Trials' principles, and completed prerecruitment and postrecruitment surveys. Respondent agreement with statements were assessed using 5-point Likert scales (from 1 ('strongly disagree') to 5 ('strongly agree')). Quantitative data were analysed using paired t-tests to compare differences pre-involvement and post-involvement. Thematic content analysis was performed on free-text data to generate recommendations for future student research involvement. Of 492 patients recruited to TWIST between 26 July 2016 and 4 March 2020, 86.0% (n=423) were recruited by medical students. Following introduction of student co-investigators (n=31), the overall monthly recruitment rate tripled (4.8-15.7 patients). 96.8% of recruiters (n=30/31) completed both surveys, and all respondents reported significant improvement in clinical and academic competencies. Three higher-level thematic domains emerged from the qualitative analysis: (1) engagement, (2) preparation and (3) ongoing support. Student recruitment in clinical trials is feasible and accelerates recruitment to clinical trials. Students demonstrated novel clinical research competencies and increased their likelihood of future involvement. Adequate training, support and selection of suitable trials are essential for future student involvement in randomised trials.


Assuntos
Pesquisa Biomédica , Estudantes de Medicina , Adulto , Humanos , Inquéritos e Questionários , Competência Clínica , Hospitais Universitários
4.
NPJ Digit Med ; 6(1): 85, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147462

RESUMO

Remote digital postoperative wound monitoring provides an opportunity to strengthen postoperative community care and minimise the burden of surgical-site infection (SSI). This study aimed to pilot a remote digital postoperative wound monitoring service and evaluate the readiness for implementation in routine clinical practice. This was a single-arm pilot implementational study of remote digital postoperative wound monitoring across two tertiary care hospitals in the UK (IDEAL stage 2b, clinicaltrials.gov: NCT05069103). Adults undergoing abdominal surgery were recruited and received a smartphone-delivered wound assessment tool for 30-days postoperatively. Patients received 30-day postoperative follow-up, including the Telehealth Usability Questionnaire (TUQ). A thematic mixed-methods approach was used, according to the WHO framework for monitoring and evaluating digital health interventions. 200 patients were enroled, of whom 115 (57.5%) underwent emergency surgical procedures. Overall, the 30-day SSI rate was 16.5% (n = 33/200), with 72.7% (n = 24) diagnosed post-discharge. Usage of the intervention was 83.0% (n = 166/200), with subsequently 74.1% (n = 123/166) TUQ completion. There were no issues reported with feasibility of the technology, with the reliability (3.87, 95% CI: 3.73-4.00) and quality of the interface rated highly (4.18, 95%: 4.06-4.30). Patient acceptance was similarly high with regards to ease of use (4.51, 95% CI: 4.41-4.62), satisfaction (4.27, 95% CI: 4.13-4.41), and usefulness (4.07, 95% CI: 3.92-4.23). Despite the desire for more frequent and personalised interactions, the majority viewed the intervention as providing meaningful benefit over routine postoperative care. Remote digital postoperative wound monitoring successfully demonstrated readiness for implementation with regards to the technology, usability, and healthcare process improvement.

5.
Lancet Digit Health ; 5(5): e295-e315, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37100544

RESUMO

An increasing number of digital health interventions (DHIs) for remote postoperative monitoring have been developed and evaluated. This systematic review identifies DHIs for postoperative monitoring and evaluates their readiness for implementation into routine health care. Studies were defined according to idea, development, exploration, assessment, and long-term follow-up (IDEAL) stages of innovation. A novel clinical innovation network analysis used coauthorship and citations to examine collaboration and progression within the field. 126 DHIs were identified, with 101 (80%) being early stage innovations (IDEAL stage 1 and 2a). None of the DHIs identified had large-scale routine implementation. There is little evidence of collaboration, and there are clear omissions in the evaluation of feasibility, accessibility, and the health-care impact. Use of DHIs for postoperative monitoring remains at an early stage of innovation, with promising but generally low-quality supporting evidence. Comprehensive evaluation within high-quality, large-scale trials and real-world data are required to definitively establish readiness for routine implementation.


Assuntos
Cuidados Pós-Operatórios , Telemedicina , Humanos
6.
ChemElectroChem ; 9(17): e202200610, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36246849

RESUMO

In this work, the dithiolene complex iron(III) bis-maleonitriledithiolene [Fe(mnt)2] is characterised and evaluated as a homogeneous CO2 reduction catalyst. Electrochemically the Fe(mnt)2 is reduced twice to the trianionic Fe(mnt)2 3- state, which is correspondingly found to be active towards CO2. Interestingly, the first reduction event appears to comprise overlapping reversible couples, attributed to the presence of both a dimeric and monomeric form of the dithiolene complex. In acetonitrile Fe(mnt)2 demonstrates a catalytic response to CO2 yielding typical two-electron reduction products: H2, CO and CHOOH. The product distribution and yield were governed by the proton source. Operating with H2O as the proton source gave only H2 and CO as products, whereas using 2,2,2-trifluoroethanol gave 38 % CHOOH faradaic efficiency with H2 and CO as minor products.

7.
ACS Appl Mater Interfaces ; 14(41): 46562-46568, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36194585

RESUMO

Microplastic (MP) pollution is a global challenge that requires immediate mitigation practices. Monitoring is crucial for quantifying MPs, but their mitigation remains very challenging due to several factors, including the lack of selective materials to specific polymers, and the low sensitivity of the current detection techniques. In this work, we introduce a novel design for the selective detection of MPs through fluorescence spectroscopy by exploiting conjugated polymer nanoparticles (CPNs). Fluorescent diketopyrrolopyrrole nanoparticles were prepared by nanoprecipitation to incorporate peripheral hyaluronic acid to increase their affinity for various plastics. The affinity of the new ligand for various types of MPs was examined through several characterization techniques, including fluorescence spectroscopy and microscopy, nanoparticle tracking analysis and computational studies. The new CPN were shown to be highly fluorescent in the presence of typically abundant MPs, achieving very strong binding constants in the picomolar range. This very strong affinity for a broad family of plastics was found to be the results of cooperative supramolecular effects and topographical affinity, as probed by advanced microscopy and in silico studies. Furthermore, the new affinity probes were shown to be highly selective for MPs, allowing for their detection in heterogeneous samples, including soil debris and other organic contaminants. The new materials design introduced in this work constitute a promising platform for the development of novel MP detection devices directly useable at the point of collection. Moreover, it opens new avenue for the mitigation of this environmental hazard through tailorable materials.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Microplásticos , Plásticos , Polímeros/química , Ácido Hialurônico , Ligantes , Monitoramento Ambiental , Nanopartículas/química , Solo , Poluentes Químicos da Água/análise
8.
Transplant Cell Ther ; 28(4): 183.e1-183.e8, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35104660

RESUMO

In the context of T-cell depletion, failing to achieve full donor chimerism (FDC) entails higher risk of graft loss and disease relapse. Donor lymphocyte infusion (DLI) is an adoptive immunotherapy for mixed chimerism (MC) or relapsed disease after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, little is known of factors associated with attaining FDC or disease remission. We carried out a retrospective study with 100 adult patients to identify patient and donor factors that can predict achievement of FDC and disease remission and describe complications after DLI. Indications for DLI were T-cell MC in 61 patients and relapsed disease in 39 patients. Forty patients (65.6%) with MC attained T-full donor chimerism (T-FDC), with higher responses seen in patients whose donors were female (81.5% versus 52.9%, P = .004) and cytomegalovirus negative (76.5% versus 52%, P = .004). However, only patients with younger donors (<30 years old) compared to older donors (94.4% versus 53.5%, P = .013) and those attaining unfractionated whole blood (UWB) FDC after DLI (76.6% versus 28.6%, P < .001) had a survival benefit and subsequently a better graft-versus-host disease (GvHD)-free/relapse-free survival. Nineteen of 39 patients (48.7%) with relapsed disease achieved remission after DLI. In this cohort, attaining T-FDC impacted favorably in disease control (76.7% versus 12.5%, P = .012) and improved survival (45.5% versus 12.5%, P = .007). In the whole population, the cumulative incidence of acute GvHD (aGvHD) at day 100 after DLI was 23%, and chronic GvHD (cGvHD) at 1 year after DLI was 22%. In the whole population, donor age was also a determining factor for aGvHD, because patients with younger donors had a lower incidence of aGvHD (8% versus 36%, P = .021). The cGvHD was more likely to occur in patients who converted to T-FDC (34% versus 10.3%, P = .025). Donor characteristics are increasingly considered when deciding approaches for HSCT. Donor age should be considered when planning HSCT, as well as doses and scheduling of DLI. As per our experience, this should be done alongside T/UWB chimerism to achieve the maximal clinical benefit with less associated toxicity. Selection of younger male donors from stem cell registries can minimize the risk of GvHD and improve survival.


Assuntos
Neoplasias Hematológicas , Imunoterapia Adotiva , Adulto , Feminino , Neoplasias Hematológicas/terapia , Humanos , Transfusão de Linfócitos , Masculino , Recidiva Local de Neoplasia , Estudos Retrospectivos , Linfócitos T , Transplante Homólogo
9.
Talanta ; 237: 122981, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736702

RESUMO

Here we show that the fluorescence of fluorescein isothiocyanate (FITC) is not altered by its reaction with primary amines. However, the fluorescence is rapidly quenched upon reaction with small molecular weight thiols including cysteine, glutathione, homocysteine, dithiothreitol, and sulfide. We have taken advantage of the thiol-dependent quenching of FITC to devise a sulfide specific assay by utilizing polydimethylsiloxane (PDMS) membranes that are permeable to hydrogen sulfide but not to larger charged thiols. In addition, we have discovered that the fluorescein dithiocarbamate (FDTC) formed by the reaction with sulfide can specifically react with S-nitrosothiols (RSNO) to regenerate FITC, thus serving as a specific, fluorogenic reagent to detect picomol levels of RSNO. FDTC was tested as an intracellular RSNO-sensor in germinating tomato seedlings (Solanum lycopersicum) via epifluorescence microscopy. Control plant roots exposed to FDTC showed low intracellular fluorescence which increased ∼3-fold upon exposure to extracellular S-nitrosoglutathione and ∼4-fold in the presence of N6022, a S-nitrosoglutathione reductase (GSNOR) inhibitor, demonstrating that FDTC can be used to visualize intracellular RSNO levels.


Assuntos
Sulfeto de Hidrogênio , S-Nitrosotióis , Fluoresceína , Isotiocianatos , Óxido Nítrico
10.
NPJ Digit Med ; 4(1): 160, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795398

RESUMO

Surgical site infections (SSI) cause substantial morbidity and pose a burden to acute healthcare services after surgery. We aimed to investigate whether a smartphone-delivered wound assessment tool can expedite diagnosis and treatment of SSI after emergency abdominal surgery. This single-blinded randomised control trial (NCT02704897) enroled adult emergency abdominal surgery patients in two tertiary care hospitals. Patients were randomised (1:1) to routine postoperative care or additional access to a smartphone-delivered wound assessment tool for 30-days postoperatively. Patient-reported SSI symptoms and wound photographs were requested on postoperative days 3, 7, and 15. The primary outcome was time-to-diagnosis of SSI (Centers for Disease Control definition). 492 patients were randomised (smartphone intervention: 223; routine care: 269). There was no significant difference in the 30-day SSI rate between trial arms: 21 (9.4%) in smartphone vs 20 (7.4%, p = 0.513) in routine care. Among the smartphone group, 32.3% (n = 72) did not utilise the tool. There was no significant difference in time-to-diagnosis of SSI for patients receiving the intervention (-2.5 days, 95% CI: -6.6-1.6, p = 0.225). However, patients in the smartphone group had 3.7-times higher odds of diagnosis within 7 postoperative days (95% CI: 1.02-13.51, p = 0.043). The smartphone group had significantly reduced community care attendance (OR: 0.57, 95% CI: 0.34-0.94, p = 0.030), similar hospital attendance (OR: 0.76, 95% CI: 0.28-1.96, p = 0.577), and significantly better experiences in accessing care (OR: 2.02, 95% CI: 1.17-3.53, p = 0.013). Smartphone-delivered wound follow-up is feasible following emergency abdominal surgery. This can facilitate triage to the appropriate level of assessment required, allowing earlier postoperative diagnosis of SSI.

11.
Langenbecks Arch Surg ; 406(8): 2781-2788, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34505198

RESUMO

PURPOSE: Complete mesocolic excision (CME) has been proposed for better local control of colon cancer and to improve cancer-specific survival (CSS). However, CME may be associated with increased morbidity from bleeding during central vascular ligation. This study aimed to investigate the outcome of conventional right hemicolectomy, a traditional anatomical dissection along anatomical planes with radical excision of the central lymph nodes at the level of the origin of colic artery but without exposure of superior mesenteric vein and artery (SMV/SMA). METHOD: This was a retrospective review of a cohort of all elective right hemicolectomies performed at a specialist tertiary unit during a five-year period (2011-2015). RESULTS: Five-hundred-nineteen patients (271 female, a median age of 73.0 years (interquartile range (IQR) 65.0-80.0)) were included (Stage I disease: 2.7%, stage II: 53.2%, stage III: 33.3%, stage IV: 10.8%). At the latest follow-up (a median 47 months (IQR 29-67)), local recurrence occurred in 34 patients (6.6%). Three-year overall survival was 74.4% and 3-year CSS was 85.9%. Subgroup analysis for stage I-III showed local recurrence in 6.0%, sole distant recurrence in 7.6% while 19 patients (4.1%) suffered concomitant local and distant recurrence. The anastomotic leak rate was 1.0% and perioperative bleeding occurred in 1.2%. CONCLUSIONS: Oncological outcomes comparable to those of CME can be achieved by conventional surgery but with low rates of bleeding complications and anastomotic leakage. The proposed advantages of CME should be carefully considered and balanced against patients' co-morbidities and potential complications.


Assuntos
Neoplasias do Colo , Laparoscopia , Mesocolo , Idoso , Colectomia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Mesocolo/cirurgia , Estudos Retrospectivos
12.
Micromachines (Basel) ; 12(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34357220

RESUMO

Anastomotic leakage (AL) is a common and dangerous post-operative complication following intestinal resection, causing substantial morbidity and mortality. Ischaemia in the tissue surrounding the anastomosis is a major risk-factor for AL development. Continuous tissue oxygenation monitoring during the post-operative recovery period would provide early and accurate early identification of AL risk. We describe the construction and testing of a miniature implantable electrochemical oxygen sensor that addresses this need. It consisted of an array of platinum microelectrodes, microfabricated on a silicon substrate, with a poly(2-hydroxyethyl methacrylate) hydrogel membrane to protect the sensor surface. The sensor was encapsulated in a biocompatible package with a wired connection to external instrumentation. It gave a sensitive and highly linear response to variations in oxygen partial pressure in vitro, although over time its sensitivity was partially decreased by protein biofouling. Using a pre-clinical in vivo pig model, acute intestinal ischaemia was robustly and accurately detected by the sensor. Graded changes in tissue oxygenation were also measurable, with relative differences detected more accurately than absolute differences. Finally, we demonstrated its suitability for continuous monitoring of tissue oxygenation at a colorectal anastomosis over a period of at least 45 h. This study provides evidence to support the development and use of implantable electrochemical oxygen sensors for post-operative monitoring of anastomosis oxygenation.

13.
Nat Chem ; 13(8): 805-810, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34112990

RESUMO

Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with 'real time' drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy.


Assuntos
Azidas/uso terapêutico , Neoplasias/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/uso terapêutico , Azidas/química , Azidas/efeitos da radiação , Doxorrubicina/análogos & derivados , Doxorrubicina/efeitos da radiação , Doxorrubicina/uso terapêutico , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Raios gama , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Indazóis/química , Indazóis/efeitos da radiação , Indazóis/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxirredução , Pró-Fármacos/química , Pró-Fármacos/efeitos da radiação , Estudo de Prova de Conceito , Pirimidinas/química , Pirimidinas/efeitos da radiação , Pirimidinas/uso terapêutico , Sulfonamidas/química , Sulfonamidas/efeitos da radiação , Sulfonamidas/uso terapêutico , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Pers Med ; 11(6)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070593

RESUMO

Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient's post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.

16.
Mol Ther Methods Clin Dev ; 21: 1-13, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-33768125

RESUMO

The increasing demand for adeno-associated virus (AAV) vectors, a result from the surging interest for their potential to cure human genetic diseases by gene transfer, tumbled on low-performing production systems. Innovative improvements to increase both yield and quality of the vector produced have become a priority undertaking in the field. In a previous study, we showed that adding a specific concentration of sodium chloride (NaCl) to the production medium resulted in a dramatic increase of AAV vector particle and infectious titers when using the herpes simplex virus (HSV) production system, both in adherent or suspension platforms. In this work, we studied additional salts and their impact on AAV vector production. We found that potassium chloride (KCl), or a combination of KCl and NaCl, resulted in the highest increase in AAV vector production. We determined that the salt-mediated effect was the most impactful when the salt was present between 8 and approximately 16 h post-infection, with the highest rate increase occurring within the first 24 h of the production cycle. We showed that the AAV vector yield increase did not result from an increase in cell growth, size, or viability. Furthermore, we demonstrated that the impact on AAV vector production was specifically mediated by NaCl and KCl independently of their impact on the osmolality of the production media. Our findings convincingly showed that NaCl and KCl were uniquely efficacious to promote up to a 10-fold increase in the production of highly infectious AAV vectors when produced in the presence of HSV. We think that this study will provide unique and important new insights in AAV biology toward the establishment of more successful production protocols.

17.
Behav Res Methods ; 53(2): 864-873, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32885386

RESUMO

The sense of taste is rarely assessed quantitatively outside of a limited number of academic and industrial laboratories, despite its role in influencing nutrition, the flavor of foods and beverages, and protection against ingestion of spoiled and toxic foodstuffs. This dearth reflects, in part, practical limitations of most taste tests, most notably their reliance on liquid stimuli for stimulus presentation or rinsing. In this study, a novel portable taste test that requires neither liquid tastants nor liquid rinses is described and validated within a clinic population. This test, termed the Waterless Empirical Taste Test (WETT®), uses stimuli that are embedded in pads of monometer cellulose located on disposable plastic strips applied to the tongue's surface. The test-retest and split-half reliability coefficients of the WETT® were 0.92 and 0.88, respectively. These respective coefficients for sucrose, NaCl, citric acid, caffeine, and MSG were 0.82 and 0.80, 0.78 and 0.77, 0.56 and 0.73, and 0.84 and 0.84. The WETT® exhibited comparable, in some cases higher, sensitivity than two comparison taste tests, the Whole Mouth Taste Test and the Taste Quadrant Taste Test, to age, sex, etiology (head trauma vs. upper respiratory infections), and phenylthiocarbamide (PTC) taste ability. This study demonstrates that a taste test that does not require liquids can be as reliable and sensitive as more traditional liquid-based taste tests to clinical alterations in taste function.


Assuntos
Feniltioureia , Paladar , Humanos , Reprodutibilidade dos Testes , Sacarose
18.
Viruses ; 12(6)2020 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-32575696

RESUMO

Adeno-associated viruses (AAVs) are small, non-pathogenic ssDNA viruses being used as therapeutic gene delivery vectors for the treatment of a variety of monogenic diseases. An obstacle to successful gene delivery is inefficient capsid trafficking through the endo/lysosomal pathway. This study aimed to characterize the AAV capsid stability and dynamics associated with this process for a select number of AAV serotypes, AAV1, AAV2, AAV5, and AAV8, at pHs representative of the early and late endosome, and the lysosome (6.0, 5.5, and 4.0, respectively). All AAV serotypes displayed thermal melt temperatures that varied with pH. The stability of AAV1, AAV2, and AAV8 increased in response to acidic conditions and then decreased at pH 4.0. In contrast, AAV5 demonstrated a consistent decrease in thermostability in response to acidification. Negative-stain EM visualization of liposomes in the presence of capsids at pH 5.5 or when heat shocked showed induced remodeling consistent with the externalization of the PLA2 domain of VP1u. These observations provide clues to the AAV capsid dynamics that facilitate successful infection. Finally, transduction assays revealed a pH and temperature dependence with low acidity and temperatures > 4 °C as detrimental factors.


Assuntos
Proteínas do Capsídeo/metabolismo , Capsídeo/metabolismo , Dependovirus/metabolismo , Lisossomos/metabolismo , Transdução Genética , Animais , Transporte Biológico/fisiologia , Linhagem Celular , Temperatura Baixa , Terapia Genética/métodos , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/metabolismo , Células Sf9 , Spodoptera
19.
Int Forum Allergy Rhinol ; 10(6): 706-712, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32282136

RESUMO

BACKGROUND: Acute viral upper respiratory tract infections are the most common cause of chronic olfactory dysfunction. In light of the seasonality of numerous viruses, the question arises as to whether the frequency and magnitude of postviral olfactory disorders (PVODs) are similarly seasonal. We sought to determine whether olfactory deficits due to influenza and non-influenza-related viruses (I-PVODs and NI-PVODs) vary in frequency or magnitude across seasons in a North American population and whether they are more prevalent or produce more severe olfactory dysfunction during colder months when host susceptibility may be increased. METHODS: This was a retrospective study of 587 patients presenting to an academic smell and taste center with either I-PVOD-related or NI-PVOD-related olfactory deficits. Chi-square and analysis of covariance (age = covariate) compared dysfunction prevalence frequencies and scores on the University of Pennsylvania Smell Identification Test (UPSIT) across calendar months and between months with the coldest and warmest air temperatures. RESULTS: For I-PVOD-related cases, both the prevalence and magnitude of smell dysfunction were highest in the colder months. However, for NI-PVOD-related cases, prevalence was higher in warmer months but, paradoxically, the magnitude of dysfunction was higher in colder months. CONCLUSION: This study shows that seasonal variations occur in both the prevalence and magnitude of PVOD-related olfactory deficits in a North American population, and that such variations differ between NI-PVOD and I-PVOD cases. The findings suggest multiple viruses are involved in producing PVOD-related olfactory deficits.


Assuntos
Transtornos do Olfato/epidemiologia , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Prevalência , Estudos Retrospectivos , Estações do Ano , Temperatura
20.
BMJ Open ; 9(10): e029620, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31585971

RESUMO

INTRODUCTION: National data suggest that surgical site infection (SSI) complicates 2%-10% of general surgery cases, although the patient-reported incidence is much higher. SSIs cause significant patient morbidity and represent a significant burden on acute healthcare services, in a cohort predominantly suitable for outpatient management. Over three-quarters of UK adults now own smartphones, which could be harnessed to improve access to care. We aim to investigate if a smartphone-delivered wound assessment tool results in earlier treatment. METHODS AND ANALYSIS: This is a randomised controlled trial aiming to recruit 500 patients across National Health Service (NHS) hospitals. All emergency abdominal surgery patients over the age of 16 who own smartphones will be considered eligible, with the exclusion of those with significant visual impairment. Participants will be randomised in a 1:1 ratio between standard postoperative care and the intervention - use of the smartphone tool in addition to standard postoperative care. The main outcome measure will be time-to-diagnosis of SSI with secondary outcome measures considering use of emergency department and general practitioner services and patient experience. Follow-up will be conducted by clinicians blinded to group allocation. Analysis of time-to-diagnosis will be by comparison of means using an independent two sample t-test. ETHICS AND DISSEMINATION: This is the first randomised controlled trial on the use of a smartphone-delivered wound assessment tool to facilitate the assessment of SSI and the impact on time-to-diagnosis. The intervention is being used in addition to standard postoperative care. The study design and protocol were reviewed and approved by Southeast Scotland Research and Ethics Committee (REC Ref: 16/SS/0072 24/05/2016). Study findings will be presented at academic conferences, published in peer-reviewed journals and are expected in 2020. A written lay summary will be available to study participants on request. TRIAL REGISTRATION NUMBER: NCT02704897; Pre-results.


Assuntos
Abdome Agudo/cirurgia , Aplicativos Móveis , Smartphone , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Infecção da Ferida Cirúrgica/diagnóstico , Abdome Agudo/complicações , Humanos , Estudos Multicêntricos como Assunto , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios/métodos , Infecção da Ferida Cirúrgica/terapia , Reino Unido
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