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1.
Thorax ; 79(7): 652-661, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38729626

RESUMEN

BACKGROUND: Diaphragmatic sleep disordered breathing (dSDB) has been recently identified as sleep dysfunction secondary to diaphragmatic weakness in Duchenne muscular dystrophy (DMD). However, scoring criteria for the identification of dSDB are missing.This study aimed to define and validate dSDB scoring criteria and to evaluate whether dSDB severity correlates with respiratory progression in DMD. METHODS: Scoring criteria for diaphragmatic apnoea (dA) and hypopnoeas (dH) have been defined by the authors considering the pattern observed on cardiorespiratory polygraphy (CR) and the dSDB pathophysiology.10 sleep professionals (physiologists, consultants) blinded to each other were involved in a two-round Delphi survey to rate each item of the proposed dSDB criteria (Likert scale 1-5) and to recognise dSDB among other SDB. The scorers' accuracy was tested against the authors' panel.Finally, CR previously conducted in DMD in clinical setting were rescored and diaphragmatic Apnoea-Hypopnoea Index (dAHI) was derived. Pulmonary function (forced vital capacity per cent of predicted, FVC%pred), overnight oxygen saturation (SpO2) and transcutaneous carbon dioxide (tcCO2) were correlated with dAHI. RESULTS: After the second round of Delphi, raters deemed each item of dA and dH criteria as relevant as 4 or 5. The agreement with the panel in recognising dSDB was 81%, kappa 0.71, sensitivity 77% and specificity 85%.32 CRs from DMD patients were reviewed. dSDB was previously scored as obstructive. The dAHI negatively correlated with FVC%pred (r=-0.4; p<0.05). The total number of dA correlated with mean overnight tcCO2 (r 0.4; p<0.05). CONCLUSIONS: dSDB is a newly defined sleep disorder that correlates with DMD progression. A prospective study to evaluate dSDB as a respiratory measure for DMD in clinical and research settings is planned.


Asunto(s)
Técnica Delphi , Diafragma , Distrofia Muscular de Duchenne , Síndromes de la Apnea del Sueño , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/fisiopatología , Humanos , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/etiología , Síndromes de la Apnea del Sueño/complicaciones , Diafragma/fisiopatología , Masculino , Polisomnografía , Índice de Severidad de la Enfermedad , Progresión de la Enfermedad , Capacidad Vital , Adolescente , Niño
2.
Inorg Chem ; 63(14): 6335-6345, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38516707

RESUMEN

Synthesis and characterization of new P(III) and P(V) bis(azido)phosphines/phosphoranes supported by an N,N'-bis(2,6-diisopropylphenyl) imidazolin-2-iminato (IPrN) ligand and their reactivity with various secondary and tertiary phosphines result in the formation of chiral and/or asymmetric mono(phosphinimino)azidophosphines via the Staudinger reaction. The reaction of IPrNP(N3)2 (2) or IPrNP(S)(N3)2 (4S) with an excess of tertiary phosphine resulted in the chemoselective formation of IPrNP(N3)(NPMe3) (7) or IPrNP(S)N3(NPR3) (5R), respectively. The chemoselective Staudinger reactivity was also observed in reactions using a secondary phosphine (HPCy2) to produce IPrNP(S)N3[NP(H)Cy2] (6a), which exists in equilibrium with a tautomeric IPrNP(S)N3[N(H)PCy2] form (6b), as confirmed by 31P-31P nuclear Overhauser effect spectroscopy (NOESY). Density functional theory (DFT) calculations point to a combination of energetically unfavorable lowest unoccupied molecular orbitals (LUMOs) and the accumulation of increasing negative charge at the terminal azido-nitrogen upon a single azide-to-phosphinimine conversion that gave rise to the observed chemoselectivity.

3.
Anaesthesia ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733063

RESUMEN

BACKGROUND: Few existing resuscitation guidelines include specific reference to intra-operative cardiac arrest, but its optimal treatment is likely to require some adaptation of standard protocols. METHODS: We analysed data from the 7th National Audit Project of the Royal College of Anaesthetists to determine the incidence and outcome from intra-operative cardiac arrest and to summarise the advanced life support interventions reported as being used by anaesthetists. RESULTS: In the baseline survey, > 50% of anaesthetists responded that they would start chest compressions when the non-invasive systolic pressure was < 40-50 mmHg. Of the 881 registry patients, 548 were adult patients (aged > 18 years) having non-obstetric procedures under the care of an anaesthetist, and who had arrested during anaesthesia (from induction to emergence). Sustained return of spontaneous circulation was achieved in 425 (78%) patients and 338 (62%) were alive at the time of reporting. In the 365 patients with pulseless electrical activity or bradycardia, adrenaline was given as a 1 mg bolus in 237 (65%). A precordial thump was used in 14 (3%) patients, and although this was associated with return of spontaneous circulation at the next rhythm check in almost three-quarters of patients, in only one of these was the initial rhythm shockable. Calcium (gluconate or chloride) and 8.4% sodium bicarbonate were given to 51 (9%) and 25 (5%) patients, but there were specific indications for these treatments in less than half of the patients. A thrombolytic drug was given to 5 (1%) patients, and extracorporeal cardiopulmonary resuscitation was used in 9 (2%) of which eight occurred during cardiac procedures. CONCLUSIONS: The specific characteristics of intra-operative cardiac arrest imply that its optimal treatment requires modifications to standard advanced life support guidelines.

4.
Biophys J ; 122(2): 442-450, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36403088

RESUMEN

A new mixed radial-angular, three-particle correlation function method in combination with unsupervised machine learning was applied to examine the emergence of the ripple phase in dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using data from atomistic molecular dynamics simulations of system sizes ranging from 128 to 4096 lipids. Based on the acyl tail conformations, the analysis revealed the presence of four distinct conformational populations of lipids in the ripple phases of the DPPC lipid bilayers. The expected gel-like (ordered; Lo) and fluid-like (disordered; Ld) lipids are found along with their splayed tail equivalents (Lo,s and Ld,s). These lipids differ, based on their gauche distribution and tail packing. The disordered (Ld) and disordered-splayed (Ld,s) lipids spatially cluster in the ripple in the groove side, that is, in an asymmetric manner across the bilayer leaflets. The ripple phase does not contain large numbers of Ld lipids; instead they only exist on the interface of the groove side of the undulation. The bulk of the groove side is a complex coexistence of Lo,Lo,s, and Ld,s lipids. The convex side of the undulation contains predominantly Lo lipids. Thus, the structure of the ripple phase is neither a simple coexistence of ordered and disordered lipids nor a coexistence of ordered interdigitating gel-like (Lo) and ordered-splayed (Lo,s) lipids, but instead a coexistence of an ordered phase and a complex mixed phase. Principal component analysis further confirmed the existence of the four lipid groups.


Asunto(s)
Membrana Dobles de Lípidos , Simulación de Dinámica Molecular , Membrana Dobles de Lípidos/química , Membrana Celular , Conformación Molecular , Aprendizaje Automático
5.
J Am Chem Soc ; 145(2): 1236-1246, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36607895

RESUMEN

Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-"light switch" complexes [Ru(dppz)2(5,5'dmb)]2+ and [Ru(PIP)2(5,5'dmb)]2+ (dppz = dipyridophenazine, 5,5'dmb = 5,5'-dimethyl-2,2'-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor-acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5'dmb)]2+ acts to block DNA replication fork progression.


Asunto(s)
Complejos de Coordinación , Rutenio , Rutenio/farmacología , Rutenio/química , Transferencia Resonante de Energía de Fluorescencia , ADN/química , Sitios de Unión , Complejos de Coordinación/farmacología , Complejos de Coordinación/química
6.
Small ; 19(44): e2303066, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37403298

RESUMEN

Amphiphilic ABA-triblock copolymers, comprised of poly(2-oxazoline) and poly(2-oxazine), can solubilize poorly water-soluble molecules in a structure-dependent manner forming micelles with exceptionally high drug loading. All-atom molecular dynamics simulations are conducted on previously experimentally characterized, curcumin-loaded micelles to dissect the structure-property relationships. Polymer-drug interactions for different levels of drug loading and variation in polymer structures of both the inner hydrophobic core and outer hydrophilic shell are investigated. In silico, the system with the highest experimental loading capacity shows the highest number of drug molecules encapsulated by the core. Furthermore, in systems with lower loading capacity outer A blocks show a greater extent of entanglement with the inner B blocks. Hydrogen bond analyses corroborate previous hypotheses: poly(2-butyl-2-oxazoline) B blocks, found experimentally to have reduced loading capacity for curcumin compared to poly(2-propyl-2-oxazine), establish fewer but longer-lasting hydrogen bonds. This possibly results from different sidechain conformations around the hydrophobic cargo, which is investigated by unsupervised machine learning to cluster monomers in smaller model systems mimicking different micelle compartments. Exchanging poly(2-methyl-2-oxazoline) with poly(2-ethyl-2-oxazoline) leads to increased drug interactions and reduced corona hydration; this suggests an impairment of micelle solubility or colloidal stability. These observations can help driving forward a more rational a priori nanoformulation design.


Asunto(s)
Curcumina , Curcumina/química , Micelas , Portadores de Fármacos/química , Polímeros/química , Oxazinas , Interacciones Hidrofóbicas e Hidrofílicas
7.
J Chem Inf Model ; 63(15): 4477-4482, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37463067

RESUMEN

Time-resolved photoluminescence (TRPL) is a powerful tool to investigate charge carrier recombination processes in emissive materials. Perovskite materials are extremely promising for applications in solar cells; however, the interpretation of their TRPL is arduous due to the complicated nature of the recombination processes occurring in these materials. We present here the PErovskite cArrier Recombination Simulator (PEARS) web tool for effortlessly and quickly fitting TRPL of perovskite materials using advanced charge carrier recombination models, allowing for the extraction of recombination rate constants and trap state concentration. PEARS is flexible and can adapt to different situations, by ignoring recombination processes or fixing known parameters (e.g., the doping concentration). The tool is publicly available at https://pears-tool.herokuapp.com.


Asunto(s)
Pyrus , Compuestos de Calcio , Óxidos
8.
Appl Opt ; 62(14): 3788-3796, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37706997

RESUMEN

This paper is the second part of a study of the grinding of three different grades of silicon carbide (SiC) under the same conditions. In this paper, subsurface damage is analyzed using magnetorheological finishing (MRF). The MRF ribbon is brought into contact with the surface and allowed to dwell for different lengths of time to produce dimples or spots at different depths. The roughness parameters are evaluated at the base of the spots. As the spot depth increases the roughness parameters decrease, eventually saturating at a steady-state value. The depth at which saturation occurs is much greater than the initial peak-to-value roughness of the surface and is therefore assumed to be correlated to the depth of subsurface damage in the material. Estimates of the damage depth are comparable to other estimates given in the literature. The validity of this technique is assessed across different grades of SiC under different grinding conditions, and limitations are identified. The study shows that the microstructure of the SiC grade is a major factor that affects the validity of the technique. The technique is suitable for SiC grades that have a more homogeneous microstructure such as chemical vapor deposited or chemical vapor composite grades. The presence of porosity as in the direct sintered grade, or the presence of a secondary phase, for example, silicon in the reaction-bonded and silicon-infiltrated grades, could hinder the technique from providing conclusive results.

9.
Aesthet Surg J ; 43(3): 308-314, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36242549

RESUMEN

BACKGROUND: Breast augmentation remains the commonest cosmetic surgical procedure worldwide, in spite of recent regulatory action. OBJECTIVES: The aim of this study was to evaluate women with breast implants attending a breast implant assessment clinic and to capture clinical and implant data in women presenting to the service. METHODS: Patients were enrolled prospectively between January 2018 and December 2021. Clinical, implant, and practitioner data were recorded. Patients reported satisfaction on size, shape, and overall outcome as well as the presence or pain. Radiological evaluation, where indicated, was performed and data were included on these findings. RESULTS: A total of 603 patients were assessed. Their mean age was 42.7 years and mean age at implantation was 29.1 years. The most common complications were capsular contracture followed by pain, waterfall deformity, and double bubble, with rupture/contracture rates increasing after the 10-year mark. The risk of double bubble was significantly lower if patients were operated on by certified practitioners (odds ratio = 0.49, P = 0.011). There was almost universally poor awareness of the risks of breast implants in patients presenting for evaluation. CONCLUSIONS: This study has shown benefit in a breast implant assessment clinic to gather information on adverse events and patient-reported outcomes following breast implant surgery. Having appropriately trained and certified practitioners perform cosmetic augmentation significantly lowers the risk of implant malposition and deformity. Any adverse event occurring within 5 years of initial surgery should be flagged as a mandatory reportable clinical indicator and trigger further investigation.


Asunto(s)
Implantación de Mama , Implantes de Mama , Contractura , Femenino , Humanos , Adulto , Implantes de Mama/efectos adversos , Estudios Prospectivos , Geles de Silicona/efectos adversos , Implantación de Mama/efectos adversos , Contractura Capsular en Implantes/etiología , Contractura/complicaciones , Contractura/cirugía , Dolor/etiología
10.
Opt Express ; 30(23): 42749-42761, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36366722

RESUMEN

Dynamic illumination using tunable freeform arrays can enable spatial light distributions of variable size with high uniformity from non-uniform sources through relatively small opposing lateral shifts applied to the freeform components. We present the design, manufacturing, and characterization of a tunable LED-based illuminator using custom freeform Alvarez arrays with commercially available optics to shorten the manufacturing cycle. The optomechanical design and manufacturing of the Alvarez lens arrays and mounting parts are presented in detail. The optical performance of the system is evaluated and compared with simulation results using a custom camera-based test station. Experimental results demonstrate and confirm the dynamic illumination concept with good uniformity.

11.
Am J Obstet Gynecol ; 227(2): 313.e1-313.e9, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35550371

RESUMEN

BACKGROUND: Postoperative opioid prescribing has historically lacked information crucial to balancing the pain control needs of the individual patient with our professional responsibility to judiciously prescribe these high-risk medications. OBJECTIVE: This study aimed to evaluate pain control, satisfaction with pain control, and opioid use among patients undergoing isolated midurethral sling randomized to 1 of 2 different opioid-prescribing regimens. STUDY DESIGN: Patients who underwent isolated midurethral sling placement from June 1, 2020, to November 22, 2021, were offered enrollment into this prospective, randomized, open-label, noninferiority clinical trial. Participants were randomized to receive either a standard prescription of ten 5-mg oxycodone tablets provided preoperatively (standard) or an opioid prescription provided only during patient request postoperatively (restricted). Preoperatively, all participants completed baseline demographic and pain surveys, including the 9-Question Central Sensitization Index, Pain Catastrophizing Scale, and Likert pain score (scale 0-10). The participants completed daily surveys for 1 week after surgery to determine the average daily pain score, number of opioids used, other forms of pain management, satisfaction with pain control, perception of the number of opioids prescribed, and need to return to care for pain management. The online Prescription Drug Monitoring Program was used to determine opioid filling in the postoperative period. The primary outcome was average postoperative day 1 pain score, and an a priori determined margin of noninferiority was set at 2 points. RESULTS: Overall, 82 patients underwent isolated midurethral sling placement and met the inclusion criteria: 40 were randomized to the standard arm, and 42 were randomized to the restricted group. Concerning the primary outcome of average postoperative day 1 pain score, the restricted arm (mean pain score, 3.9±2.4) was noninferior to the standard arm (mean pain score, 3.7±2.7; difference in means, 0.23; 95% confidence interval, -∞ to 1.34). Of note, 23 participants (57.5%) in the standard arm vs 8 participants (19.0%) in the restricted arm filled an opioid prescription (P<.001). Moreover, 18 of 82 participants (22.0%) used opioids during the 7-day postoperative period, with 10 (25.0%) in the standard arm and 8 (19.0%) in the restricted arm using opioids (P=.52). Of participants using opioids, the average number of tablets used was 3.4±2.3, and only 3 participants used ≥5 tablets. On a scale of 1="prescribed far more opioids than needed" to 5="prescribed far less opioids than needed," the means were 1.9±1.0 in the standard arm and 2.7±1.0 in the restricted arm (P<.001). CONCLUSION: Restricted opioid prescription was noninferior to standard opioid prescription in the setting of pain control and satisfaction with pain control after isolated midurethral placement. Participants in the restricted arm filled fewer opioid prescriptions than participants in the standard arm. On average, only 3.4 tablets were used by those that filled prescriptions in both groups. Restrictive opioid-prescribing practices may reduce unused opioids in the community while achieving similar pain control.


Asunto(s)
Analgésicos Opioides , Cabestrillo Suburetral , Analgésicos Opioides/uso terapéutico , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en Medicina , Estudios Prospectivos
12.
Phys Chem Chem Phys ; 24(29): 17852-17861, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35851795

RESUMEN

Several strategies have been considered in search of more efficient organic materials for charge transfer in photovoltaic devices. Among them, the integration of donor-acceptor (D-A) functional units on a conjugated copolymer has been widely applied. In this framework, we evaluated four terpolymers made up of donor moieties derived from 9,9-dioctylfluorene and 9-(heptadecan-9-yl)-9H-carbazole combined with 2,1,3-benzothiadiazole, the acceptor moiety, in different monomer ratios and polymerization routes (block and random microstructures). The preferred molecular orientation and charge transfer dynamics of the polymeric films were assessed by near edge X-ray absorption fine structure spectroscopy (NEXAFS) and resonant Auger electron spectroscopy (RAES) around the sulfur K-edge. Charge transfer times (τCT) were estimated by the Core-Hole Clock (CHC) method. Films with a high degree of organization were identified for the block terpolymer and random terpolymers with uneven amounts of donor units, showing a preferred orientation of the benzothiadiazole (BT) molecular plane parallel to the substrate surface. The values of τCT measured for all terpolymers were higher than those for typical polymers used in photovoltaic devices, which is not desirable for this type of optoelectronic application, but this may be correlated to the strong acceptor character of BT, the unit probed. To investigate the effect of film formation on the excited state behavior, steady-state and time-resolved photoluminescence measurements were also conducted. X-ray photoelectron spectroscopy (XPS) was employed to characterize the surface chemical composition of the terpolymer films. Based on the spectroscopic data the block copolymer appears to be the most suitable for the desired application.

13.
Appl Opt ; 61(15): 4579-4590, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-36256301

RESUMEN

This paper presents a study of the grinding of three different grades of silicon carbide (SiC) under the same conditions. Surface topography is analyzed using coherent scanning interferometry and scanning electron microscopy. The study provides a baseline understanding of the process mechanics and targets effective selection of process parameters for grinding SiC optics with near optical level surface roughness, thus reducing the need for post-polishing. Samples are raster and spiral ground on conventional precision machines with metal and copper-resin bonded wheels under rough, medium, and finish grinding conditions. Material microstructure and grinding conditions affect attainable surface roughness. Local surface roughness of less than 3 nm RMS was attained in both chemical vapor deposition (CVD) and chemical vapor composite (CVC) SiC. The tool footprint is suitable for sub-aperture machining of a large freeform optics possibly without the need for surface finish correction by post-polishing. Subsurface damage will be assessed in Part 2 of this paper series.

14.
J Emerg Med ; 62(2): e13-e15, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35027230

RESUMEN

BACKGROUND: Cortical hand strokes affect the 'hand knob' of the motor cortex, resulting in isolated distal upper limb or hand weakness. They are rare and can be easily misdiagnosed for peripheral lesions. CASE REPORTS: Case 1: A 59-year-old man presented to the Emergency Department (ED) after noticing left hand weakness while driving. There was no sensory deficit noted. A full neurological examination suggested an upper motor neurone rather than a peripheral nerve lesion. This was confirmed by a magnetic resonance imaging scan of his brain. Case 2: An 88-year-old man presented to the ED after developing sudden-onset left hand weakness while completing a newspaper puzzle. Power returned gradually over approximately 4 h, with no sensory symptoms being noted. A transient ischemic attack leading to cortical hand was diagnosed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cortical hand strokes are a rare, but important, differential for wrist drop. They are often first strokes and embolic in nature. Therefore, correct diagnosis is vital to enable initiation of secondary prevention.


Asunto(s)
Mano , Corteza Motora , Anciano de 80 o más Años , Servicio de Urgencia en Hospital , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Extremidad Superior
15.
Sensors (Basel) ; 22(12)2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35746433

RESUMEN

High-resolution hyperspectral imaging is becoming indispensable, enabling the precise detection of spectral variations across complex, spatially intricate targets. However, despite these significant benefits, currently available high-resolution set-ups are typically prohibitively expensive, significantly limiting their user base and accessibility. These limitations can have wider implications, limiting data collection opportunities, and therefore our knowledge, across a wide range of environments. In this article we introduce a low-cost alternative to the currently available instrumentation. This instrument provides hyperspectral datasets capable of resolving spectral variations in mm-scale targets, that cannot typically be resolved with many existing low-cost hyperspectral imaging alternatives. Instrument metrology is provided, and its efficacy is demonstrated within a mineralogy-based environmental monitoring application highlighting it as a valuable addition to the field of low-cost hyperspectral imaging.


Asunto(s)
Monitoreo del Ambiente , Imágenes Hiperespectrales , Monitoreo del Ambiente/métodos
16.
J Environ Manage ; 311: 114822, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35255324

RESUMEN

Energy and environmental challenges are global concerns that scientists are interested in alleviating. It is on this premise that we prepared boron/nitrogen graphene-coated Cu0/TiO2 (B/N-graphene-coated Cu/TiO2) photocatalyst of varying B:N ratios with dual functionality of H2 production and 2-Chlorophenol (2-CP) degradation. In-situ coating of Cu0 with B/N-graphene is achieved via solvothermal synthesis and calcination under an inert atmosphere. All B/N-graphene-coated Cu/TiO2 exhibit higher photonic efficiencies (5.68%-7.06% at 300 < λ < 400 nm) towards H2 production than bare TiO2 (0.25% at 300 < λ < 400 nm). Varying the B:N ratio in graphene influences the efficiency of H2 generation. A B:N ratio of 0.08 yields the most active composite exhibiting a photonic efficiency of 7.06% towards H2 evolution and a degradation rate of 4.07 × 10-2 min-1 towards 2-chlorophenol (2-CP). Density functional theory (DFT) investigations determine that B-doping (p-type) enhances graphene stability on Cu0 while N-doping (n-type) increases the reduction potential of Cu0 relative to H+ reduction potential. X-ray photoelectron spectroscopy reveals that increasing the B:N ratio increases p-type BC2O while decreasing n-type pyridinic-N in graphene thus altering the interlayer electron density. Isotopic labelling experiments determine water reduction as the main mechanism by which H2 is produced over B/N-graphene-coated Cu/TiO2. The reactive species involved in the degradation of 2-CP are holes (h+), hydroxyl radical (OH•), and O2•-, of which superoxide (O2•-) plays the major role. This work displays B/N -graphene-coated Cu/TiO2 as a potential photocatalyst for large-scale H2 production and 2-CP degradation.

17.
PLoS Pathog ; 15(12): e1008101, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31877175

RESUMEN

Active efflux due to tripartite RND efflux pumps is an important mechanism of clinically relevant antibiotic resistance in Gram-negative bacteria. These pumps are also essential for Gram-negative pathogens to cause infection and form biofilms. They consist of an inner membrane RND transporter; a periplasmic adaptor protein (PAP), and an outer membrane channel. The role of PAPs in assembly, and the identities of specific residues involved in PAP-RND binding, remain poorly understood. Using recent high-resolution structures, four 3D sites involved in PAP-RND binding within each PAP protomer were defined that correspond to nine discrete linear binding sequences or "binding boxes" within the PAP sequence. In the important human pathogen Salmonella enterica, these binding boxes are conserved within phylogenetically-related PAPs, such as AcrA and AcrE, while differing considerably between divergent PAPs such as MdsA and MdtA, despite overall conservation of the PAP structure. By analysing these binding sequences we created a predictive model of PAP-RND interaction, which suggested the determinants that may allow promiscuity between certain PAPs, but discrimination of others. We corroborated these predictions using direct phenotypic data, confirming that only AcrA and AcrE, but not MdtA or MsdA, can function with the major RND pump AcrB. Furthermore, we provide functional validation of the involvement of the binding boxes by disruptive site-directed mutagenesis. These results directly link sequence conservation within identified PAP binding sites with functional data providing mechanistic explanation for assembly of clinically relevant RND-pumps and explain how Salmonella and other pathogens maintain a degree of redundancy in efflux mediated resistance. Overall, our study provides a novel understanding of the molecular determinants driving the RND-PAP recognition by bridging the available structural information with experimental functional validation thus providing the scientific community with a predictive model of pump-contacts that could be exploited in the future for the development of targeted therapeutics and efflux pump inhibitors.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Proteínas de Transporte de Membrana/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Infecciones Bacterianas/tratamiento farmacológico , Proteínas Bacterianas/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Transporte Biológico/efectos de los fármacos , Proteínas Portadoras/metabolismo , Femenino , Proteínas de Transporte de Membrana/metabolismo , Ratones Endogámicos BALB C , Periplasma/efectos de los fármacos , Periplasma/metabolismo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/metabolismo
18.
Appl Opt ; 60(3): 681-696, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33690438

RESUMEN

Additive manufacturing is a disruptive technology that can be leveraged by the redesign of components in most engineering fields. Fundamental engineering resources for lightweight mirrors were developed more than 30 years ago with a main design limitation, state of the art manufacturing. Here, we present two design methodologies for the design of lightweight mirrors. The first method utilizes analytical expressions to design a traditional isogrid mirror, which provided the foundation for most lightweight mirrors to date. The second method employs a combination of topology optimization, lattice infill, and analytical estimation to develop an advanced lightweight mirror designed for additive manufacturing. The advanced mirror design outperforms the traditional design for each functional requirement, including a 94% reduction in predicted surface quilting and a higher specific stiffness. The manufacturing of the advanced mirror is only possible with an additive manufacturing process.

19.
Intern Med J ; 51(1): 52-61, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32043691

RESUMEN

BACKGROUND: Residual kidney function (RKF) has been associated with improved solute clearance and survival in haemodialysis (HD) patients. However, whether RKF impacts symptom burden in HD patients is unknown. AIMS: To determine the prevalence of RKF in HD patients and to explore associations between higher levels of RKF with symptom burden, as well as clinical and biochemical parameters. METHODS: This is a single-centre, retrospective, observational study. RKF was assessed as urea clearance (KRU) by interdialytic urine collection. Symptom burden was measured using the palliative care outcome scale renal questionnaire. RESULTS: A total of 90 maintenance HD patients was recruited; 31.9% had KRU ≥1 mL/min/1.73 m2 . Patients with KRU ≥1 mL/min/1.73 m2 reported fewer symptoms (5.3 ± 3.5 vs 7.7 ± 3.8) (P = 0.011), including less shortness of breath (15% vs 55%) (P = 0.0013) and vomiting (0% vs 30%) (P = 0.0016). Higher RKF was associated with lower ß2 -microglobilin (P < 0.0001), and lower serum potassium (P = 0.02), but no difference in phosphate, haemoglobin, C-reactive protein or serum albumin. CONCLUSION: Higher RKF was significantly associated with fewer symptoms, and lower serum ß2 -microglobulin and potassium, suggesting that strategies to preserve RKF may be beneficial.


Asunto(s)
Fallo Renal Crónico , Tasa de Filtración Glomerular , Humanos , Riñón , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Estudios Retrospectivos
20.
Intern Med J ; 51(10): 1691-1699, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33463895

RESUMEN

BACKGROUND: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment. No Australian guidelines address driving safety in dialysis patients. AIMS: To estimate the proportion of dialysis patients who were driving and those at risk of driving impairment, and to investigate the agreement between objective and subjective markers of risk. METHODS: This single-centre study involved dialysis patients voluntarily completing two questionnaires relating to risk of driving impairment; the first questionnaire focussed on objective markers, and the second questionnaire focussed on subjective markers. Risk of driving impairment was established using pre-determined criteria, and the agreement between objective and subjective markers was estimated using Cohen kappa. RESULTS: A total of 44.8% (99/221) of patients participated; 76.8% (76/99) of participants were driving, and 76.3% (58/76) of drivers were at risk of driving impairment. Factors associated with at-risk driving included post dialysis dizziness, leg weakness or numbness, falling asleep while driving and hypoglycaemia. Sixteen patients reported collisions since commencing dialysis. The questionnaires displayed slight agreement (Cohen kappa = 0.20) between objective and subjective markers. CONCLUSIONS: Dialysis patients are at risk of driving impairment based on self-reported questionnaire responses. Discrepancies between patients' perceptions and objective markers were apparent. Further research into appropriate risk assessments, as well as development of guidelines to aid in determining driving safety in dialysis patients, is needed.


Asunto(s)
Conducción de Automóvil , Disfunción Cognitiva , Fallo Renal Crónico , Accidentes de Tránsito , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal , Encuestas y Cuestionarios
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