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1.
Nanoscale ; 15(45): 18241-18249, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37947459

RESUMO

In order to trap nanoparticles with dielectrophoresis, high electric field gradients are needed. Here we created large area (>mm2) conductive carbon nanofiber mats to trap nanoparticles with dielectrophoresis. The electrospun fiber mats had an average diameter of 267 ± 94 nm and a conductivity of 2.55 S cm-1. Relative to cleanroom procedures, this procedure is less expensive in creating bulk conductive nanoscale features. The electrospun fiber mat was used as one electrode, with an indium-tin-oxide glass slide serving as the other (separated approximately 150 µm). Numerical models showed that conductive nanoscale fibers can generate significant field gradients sufficient to overcome Brownian transport of nanoparticles. Our experiments trapped 20 nm fluorescent polystyrene beads at 7 Vrms and 1 kHz. Trapping is further enhanced through simultaneous electrohydrodynamic motion. Overall, this straightforward electrospun fiber mat can serve as a foundation for future use in microscale electrokinetic devices.

2.
J Med Chem ; 66(13): 8929-8950, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37314941

RESUMO

An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory eye drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, and water-soluble JAK inhibitors as immunomodulating agents for topical ocular disposition. A focused library of known 3-(4-(2-(arylamino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitriles was evaluated as a molecular starting point. Structure-activity relationships (SARs) revealed a ligand-efficient (LE) JAK inhibitor series, amenable to aqueous solubility. Subsequent in vitro analysis indicated the potential for off-target toxicity. A KINOMEscan selectivity profile of 5 substantiated the likelihood of widespread series affinity across the human kinome. An sp2-to-sp3 drug design strategy was undertaken to attenuate off-target kinase activity while driving JAK-STAT potency and aqueous solubility. Tactics to reduce aromatic character, increase fraction sp3 (Fsp3), and bolster molecular complexity led to the azetidin-3-amino bridging scaffold in 31.


Assuntos
Inibidores de Janus Quinases , Humanos , Janus Quinase 1 , Janus Quinase 2 , Janus Quinase 3 , Inibidores de Janus Quinases/farmacologia , Janus Quinases , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Solubilidade
4.
J Ocul Pharmacol Ther ; 39(2): 117-127, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36602977

RESUMO

Purpose: A new class of ocular steroids designed to mitigate steroid-induced intraocular pressure (IOP) elevation while maintaining anti-inflammatory activity was developed. Herein is described the discovery and preclinical characterization of ROCK'Ster compound 1. Methods: Codrugs consisting of a Rho kinase inhibitor (ROCKi) and a corticosteroid were synthesized. Compounds were initially screened in vitro for ROCKi activity and anti-inflammatory activity against the proinflammatory interleukin 23 and bacterial lipopolysaccharide (LPS) pathways. Selected compounds were then screened for solubility, chemical stability, and ex vivo corneal metabolism. Lead compound 1 was evaluated for IOP lowering in the Dutch Belted rabbit and for anti-inflammatory efficacy in both a postcataract surgery model and an allergic eye disease (AED) mouse model. Results: Several ROCK'Sters were found to be potent inhibitors of ROCK (Kis < 50 nM), have high anti-inflammatory activity in vitro (IC50s < 50 nM), display sufficient stability in topical ophthalmic formulations, and have a moderate rate of corneal metabolism. Compound 1 (0.1% and 0.25%, quater in die [QID]-4 times a day) demonstrated IOP-lowering capability without inducing hyperemia in our rabbit model. When compared with the marketed steroids, Durezol® and Pred Forte®, compound 1 (0.1%, 0.25%) demonstrated noninferiority in clinical scoring in a rabbit model of inflammation after surgery. In addition, anti-inflammatory outcomes were observed with compound 1 (0.1%) relative to Lotemax® or vehicle control in an AED mouse model. Conclusion: ROCK'Ster compound 1 is a novel compound suitable for topical ocular dosing that possesses IOP-lowering capability along with similar anti-inflammatory activity compared with marketed steroids.


Assuntos
Oftalmopatias , Pressão Intraocular , Animais , Camundongos , Coelhos , Quinases Associadas a rho , Oftalmopatias/tratamento farmacológico , Modelos Animais de Doenças , Corticosteroides , Córnea , Soluções Oftálmicas/farmacologia , Anti-Hipertensivos
5.
BMC Public Health ; 23(1): 183, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707792

RESUMO

Granted by the U.S. Food and Drug Administration, an Emergency Use Authorization (EUA) can only be utilized upon declaration that a specialized set of circumstances exist which justify the authorization. In 2020, the COVID-19 pandemic demanded rapid communication strategies to promote treatment options available through EUA. Despite the authorizations of available monoclonal antibody (mAb) treatments in November 2020, their rate of adoption among health care providers in the U.S. remained low well into 2021. This study examines the accelerators and barriers to provider adoption of COVID-19 treatment so that future adoption of treatments in emerging public health emergencies may be better communicated and hastened. We established a framework informed by adoption accelerators and barriers identified by Diffusion of Innovations (DoI) Theory and conducted a study during the rapidly evolving COVID-19 public health emergency. Most DoI public health research focuses on chronic health issues and has yet to be applied to provider adoption of new treatment under EUA. Through a series of guided interviews with health care providers, primarily physicians or nurse practitioners that were responsible for referring COVID-19 patients, we extracted tools, processes, or other mechanisms (accelerators) and barriers to validate against our DoI framework and fill the gap regarding emergency situations. Our research found that providers supported by large health systems were more inclined to adoption, due to many contributing factors such as the availability of collaborative support and availability of information. Further, communicating evidence-based summaries of treatment options and related processes was also critical to adoption.


Assuntos
COVID-19 , Saúde Pública , Humanos , COVID-19/epidemiologia , Pandemias , Tratamento Farmacológico da COVID-19 , Pessoal de Saúde
6.
ANZ J Surg ; 93(4): 939-944, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36350028

RESUMO

BACKGROUND: Computed tomographic colonography (CTC) is sensitive to polyp detection but is considered inaccurate for measuring diminutive polyps (<6 mm), with divergence between CTC and either colonoscopic or histopathological polyp measurements. Reporting diminutive polyps remains debatable. This study aims to compare outcomes of symptomatic patients with diminutive versus borderline polyps on CTC and to thereby examine the potential implication of reporting diminutive polyps. METHODS: A single-centre retrospective study of symptomatic patients who underwent CTC from October 2016 through September 2018 was performed. After excluding CTC demonstrating cancer, no polyps, or polyps >6 mm, cases were categorized as either 'diminutive' (largest polyp <6 mm), or 'borderline' (largest polyp = 6 mm). The outcome measures were progression to endoscopy, surgery, procedure-related morbidity, dysplasia and malignancy. RESULTS: A total of 308 cases (211 diminutive and 97 borderline) were analysed. The groups were similar (P > 0.05) in mean age (73 vs. 74 years), female proportion (57% vs. 49%), endoscopy-related morbidity (6% vs. 7%) and CTC-related morbidity (0 vs. 1%). Most patients (64%) underwent endoscopy, which was more common in the borderline vs. the diminutive group (76% vs. 59%; P = 0.003). Dysplasia was more common in the borderline vs. the diminutive group (69% vs. 48%; P = 0.003). No malignancies were diagnosed, and no patients proceeded to surgery. CONCLUSION: Reporting diminutive polyps on CTC for symptomatic patients frequently leads to endoscopy, which often reveals dysplasia but rarely malignancy. This raises the question of how referring clinicians can best counsel and manage symptomatic patients with diminutive polyps on CTC, by considering the balance between utilitarianism and deontology.


Assuntos
Pólipos do Colo , Colonografia Tomográfica Computadorizada , Humanos , Feminino , Colonografia Tomográfica Computadorizada/métodos , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/cirurgia , Estudos Retrospectivos , Colonoscopia/métodos , Colonoscópios
7.
Retina ; 43(1): 25-33, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36542081

RESUMO

PURPOSE: AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion. METHODS: Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response). RESULTS: Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were -93 µm and -211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control. CONCLUSION: Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Dexametasona , Glucocorticoides , Resultado do Tratamento , Implantes de Medicamento , Tomografia de Coerência Óptica , Injeções Intravítreas
9.
Lab Chip ; 22(23): 4705-4716, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36349980

RESUMO

We introduce a microfluidic impedance platform to electrically monitor in real-time, endothelium monolayers undergoing fluid shear stress. Our platform incorporates sensing electrodes (SEs) that measure cell behavior and cell-free control electrodes that measure cell culture media resistance simultaneously but independently from SEs. We evaluated three different cellular subpopulations sizes through 50, 100, and 200 µm diameter SEs. We tested their utility in measuring the response of human umbilical vein endothelial cells (HUVECs) at static, constant (17.6 dyne per cm2), and stepped (23.7-35-58.1 dyne per cm2) shear stress conditions. For 14 hours, we collected the impedance spectra (100 Hz-1 MHz) of sheared cells. Using equivalent circuit models, we extracted monolayer permeability (RTER), cell membrane capacitance, and cell culture media resistance. Platform evaluation concluded that: (1) 50 µm SEs (∼2 cells) suffered interfacial capacitance and reduced cell measurement sensitivity, (2) 100 µm SEs (∼6 cells) was limited to measuring cell behavior only and cannot measure cell culture media resistance, and (3) 200 µm SEs (∼20 cells) detected cell behavior with accurate prediction of cell culture media resistance. Platform-based shear stress studies indicated a shear magnitude dependent increase in RTER at the onset of acute flow. Consecutive stepped shear conditions did not alter RTER in the same magnitude after shear has been applied. Finally, endpoint staining of VE-cadherin on the actual SEs and endpoint RTER measurements were greater for 23.7-35-58.1 dyne per cm2 than 17.6 dyne per cm2 shear conditions.


Assuntos
Endotélio Vascular , Microfluídica , Humanos , Impedância Elétrica , Células Cultivadas , Estresse Mecânico , Células Endoteliais da Veia Umbilical Humana
10.
Ecol Evol ; 12(8): e9209, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36035269

RESUMO

Migratory species have geographically separate distributions during their annual cycle, and these areas can vary between populations and individuals. This can lead to differential stress levels being experienced across a species range. Gathering information on the areas used during the annual cycle of red-throated divers (RTDs; Gavia stellata) has become an increasingly pressing issue, as they are a species of concern when considering the effects of disturbance from offshore wind farms and the associated ship traffic. Here, we use light-based geolocator tags, deployed during the summer breeding season, to determine the non-breeding winter location of RTDs from breeding locations in Scotland, Finland, and Iceland. We also use δ15N and δ13C isotope signatures, from feather samples, to link population-level differences in areas used in the molt period to population-level differences in isotope signatures. We found from geolocator data that RTDs from the three different breeding locations did not overlap in their winter distributions. Differences in isotope signatures suggested this spatial separation was also evident in the molting period, when geolocation data were unavailable. We also found that of the three populations, RTDs breeding in Iceland moved the shortest distance from their breeding grounds to their wintering grounds. In contrast, RTDs breeding in Finland moved the furthest, with a westward migration from the Baltic into the southern North Sea. Overall, these results suggest that RTDs breeding in Finland are likely to encounter anthropogenic activity during the winter period, where they currently overlap with areas of future planned developments. Icelandic and Scottish birds are less likely to be affected, due to less ship activity and few or no offshore wind farms in their wintering distributions. We also demonstrate that separating the three populations isotopically is possible and suggest further work to allocate breeding individuals to wintering areas based solely on feather samples.

11.
Micromachines (Basel) ; 13(2)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35208412

RESUMO

The electric curtain is a platform developed to lift and transport charged particles in air. Its premise is the manipulation of charged particles; however, fewer investigations isolate dielectric forces that are observed at lower voltages (i.e., less than the Paschen limit). This work focuses on observations of simultaneous dielectrophoretic and electrostatic forces. The electric curtain was a printed circuit board with interdigitated electrodes (0.020 inch width and spacing) coated with a layer of polypropylene, where a standing wave or travelling wave AC signal was applied (50 Hz) to produce an electric field below the Paschen limit. Soda lime glass beads (180-212 µm) demonstrated oscillatory rolling via dielectrophoretic forces. In addition, several particles simultaneously experienced rapid projectile repulsion, a behavior consistent with electrostatic phenomena. This second result is discussed as a particle-induced local increase in the electric field, with simulations demonstrating that a particle in close proximity to the curtain's surface produces a local field enhancement of over 2.5 times. The significance of this is that individual particles themselves can trigger electrostatic repulsion in an otherwise dielectric system. These results could be used for advanced applications where particles themselves provided triggered responses, perhaps for selective sorting of micrometer particles in air.

12.
eNeuro ; 9(1)2022.
Artigo em Inglês | MEDLINE | ID: mdl-34980662

RESUMO

Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response (CER) procedure. A flashing light was used as the conditioned stimulus (CS), and conditioned suppression was used to index conditioned fear. In experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin before CS pre-exposure and conditioning markedly reduced fear conditioning to both the CS and context; LI was evident in saline-infused controls but could not be detected in picrotoxin-infused rats because of the low level of fear conditioning to the CS. In experiment 2, VH picrotoxin infusions only before CS pre-exposure did not affect the acquisition of fear conditioning or LI. Together, these findings indicate that VH neural disinhibition disrupts contextual and elemental fear conditioning, without affecting the acquisition of LI. The disruption of fear conditioning resembles aversive conditioning deficits reported in schizophrenia and may reflect a disruption of neural processing both within the hippocampus and in projection sites of the hippocampus.


Assuntos
Medo , Hipocampo , Animais , Condicionamento Clássico , Condicionamento Psicológico , Masculino , Memória , Ratos
13.
Cardiovasc Eng Technol ; 13(4): 624-637, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35013917

RESUMO

PURPOSE: Pediatric heart failure patients remain in critical need of a dedicated mechanical circulatory support (MCS) solution as development efforts for specific pediatric devices continue to fall behind those for the adult population. The Inspired Pediatric VAD is being developed as a pediatric specific MCS solution to provide up to 30-days of circulatory or respiratory support in a compact modular package that could allow for patient ambulation during treatment. METHODS: Hydrodynamic performance (flows, pressures), impeller/rotor mechanical properties (torques, forces), and flow shear stress and residence time distributions of the latest design version, Inspired Pediatric VAD V3, were numerically predicted and investigated using computational fluid dynamics (CFD) software (SolidWorks Flow Simulator). RESULTS: Hydrodynamic performance was numerically predicted, indicating no change in flow and pressure head compared to the previous device design (V2), while displaying increased impeller/rotor torques and translation forces enabled by improved geometry. Shear stress and flow residence time volumetric distributions are presented over a range of pump rotational speeds and flow rates. At the lowest pump operating point (3000 RPM, 0.50 L/min, 75 mmHg), 79% of the pump volume was in the shear stress range of 0-10 Pa with < 1% of the volume in the critical range of 150-1000 Pa for blood damage. At higher speed and flow (5000 RPM, 3.50 L/min, 176 mmHg), 65% of the volume resided in the 0-10 Pa range compared to 2.3% at 150-1000 Pa. CONCLUSIONS: The initial computational characterization of the Inspired Pediatric VAD V3 is encouraging and future work will include device prototype testing in a mock circulatory loop and acute large animal model.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Animais , Desenho de Equipamento , Insuficiência Cardíaca/terapia , Humanos , Hidrodinâmica , Pressão , Estresse Mecânico
14.
Cardiovasc Eng Technol ; 13(2): 307-317, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34518953

RESUMO

PURPOSE: Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. METHODS: A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5 L/min), and pressures (0 to ~ 420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. RESULTS: The pediatric VAD produced flows as high as 4.27 L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. CONCLUSIONS: The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Animais , Criança , Desenho de Equipamento , Insuficiência Cardíaca/terapia , Hemodinâmica , Humanos , Ovinos , Torque
15.
J Colloid Interface Sci ; 607(Pt 2): 1402-1410, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34587527

RESUMO

HYPOTHESIS: Self-assembled colloidal mobility out of a non-equilibrium system can depend on many external and interparticle forces including hydrodynamic forces. While the driving forces guiding colloidal suspension, translation and self-assembly are different and unique, hydrodynamic forces are always present and can significantly influence particle motion. Unfortunately, these interparticle hydrodynamic interactions are typically overlooked. EXPERIMENTS: Here, we studied the collective behavior of colloidal particles (4.0 µm PMMA), located near the solid surface in a fluid medium confined in a cylindrical cell (3.0 mm diameter, 0.25 mm height) which was rotated vertically at a low rotational speed (20 rpm). The observed colloidal behavior was then validated through a Stokesian dynamics simulation where the concept of hydrodynamic contact force or lubrication interactions are avoided which is not physically intuitive and mathematically cumbersome. Rather, we adopted hard-sphere like colloidal collision or mobility model, while adopting other useful simplification and approximations. FINDINGS: Upon particles settling in a circular orbit, they hydrodynamically interact with each other and evolve in different structures depending on the pattern of gravity forces. Their agglomeration is a function of the applied rotation scheme, either forming colloidal clusters or lanes. While evolving into dynamic structures, colloids also laterally migrate away from the surface.


Assuntos
Coloides , Hidrodinâmica , Fenômenos Mecânicos , Movimento (Física)
16.
Colloid Interface Sci Commun ; 40: 100338, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34722169

RESUMO

This manuscript describes the potentially significant role of interfacial tension in viral infection. Our hypothesis is based on evidence from drop coalescence hydrodynamics. A change in membrane tension can trigger fusion between the vesicle and cell such that genetic material, like viral RNA, can subsequently be transported to the cell interior. In other cases, RNA may reside near the cell membrane inside the cell, which could make their removal energetically unfavorable because of hydrodynamic interactions between membrane and RNA. Interfacial tension of the virus membrane can be modulated by temperature, among many other factors, of the mucosa layer. We discuss our hypothesis within the scope of recent SARS-CoV-2 studies where temperature-dependent membrane surface tension could be impacted through different atmospheric conditions, air conditioning systems, and the use of masks.

17.
Electrophoresis ; 42(23): 2483-2489, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34409621

RESUMO

Trapping, sorting, transportation, and manipulation of synthetic microparticles and biological cells enable investigations in their behavior and properties. Microfluidic techniques like rapid electrokinetic patterning (REP) provide a non-invasive means to probe into the nature of these micro and nanoparticles. The opto-electrically induced nature of a REP micro vortex allows tuning of the trap characteristics in real-time. In this work, we studied the effects of transient optical heating on the induced electrothermal vortex using micro-particle image velocimetry (µ-PIV) and computational modeling. A near infra-red (980 nm) laser beam was focused on a colloidal suspension of 1 µm polystyrene beads sandwiched between two parallel-plate electrodes. The electrodes were subjected to an AC current. The laser spot was scanned back-and-forth in a line, at different frequencies, to create the transient vortex. This phenomenon was also studied with a computational model made using COMSOL Multiphysics. We visualize fluid flow in custom-shaped REP traps by superposing multiple axisymmetric (spot) vortices and discuss the limitations of using superposition in dynamically changing traps.


Assuntos
Microfluídica , Simulação por Computador , Eletrodos , Técnicas Analíticas Microfluídicas , Reologia
18.
Scand J Med Sci Sports ; 31(6): 1324-1334, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33560529

RESUMO

A better insight into injuries in elite-youth football may inform prevention strategies. The purpose of this prospective cohort study was to investigate the frequency, incidence, and pattern of time-loss injuries in an elite male football academy, exploring injuries in relation to age and maturation status. Across four consecutive playing seasons, playing exposure and injuries to all academy players (U'9 to U'21) were recorded by club medical staff. Maturation status at the time of injury was also calculated for players competing in U'13 to U'16 aged squads. Time-loss injury occurrence and maturation status at time of injury were the main outcome measures. A total of 603 time-loss injuries were recorded, from 190 different players. Playing exposure was 229 317 hours resulting in an overall injury rate of 2.4 p/1000 h, ranging from 0.7 p/1000 h (U'11) to 4.8 p/1000 h (U'21). Most injuries were traumatic in mechanism (73%). The most common injury location was the thigh (23%), and the most common injury type was muscle injury (29%) combining to provide the most common injury diagnosis; thigh muscle injury (17%). In U'13-U'16 players, a higher number of injuries to early-maturing players were observed in U'13-U'14 players, while more injuries to U'15-U'16 players occurred when classed as "on-time" in maturity status. Maturation status did not statistically relate to injury pattern; however, knee bone (not-fracture) injuries peaked in U'13 players while hip/groin muscle injuries peaked in U'15 players.


Assuntos
Absenteísmo , Futebol/lesões , Esportes Juvenis/lesões , Adolescente , Fatores Etários , Traumatismos do Tornozelo/epidemiologia , Atletas , Inglaterra/epidemiologia , Virilha/lesões , Crescimento/fisiologia , Lesões do Quadril/epidemiologia , Humanos , Incidência , Escala de Gravidade do Ferimento , Traumatismos do Joelho/epidemiologia , Masculino , Músculo Esquelético/lesões , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Ruptura/epidemiologia , Estações do Ano , Futebol/fisiologia , Futebol/estatística & dados numéricos , Entorses e Distensões/epidemiologia , Estatísticas não Paramétricas , Coxa da Perna/lesões , Fatores de Tempo , Esportes Juvenis/fisiologia , Esportes Juvenis/estatística & dados numéricos
19.
Appl Biosaf ; 26(2): 80-89, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36034691

RESUMO

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused a global shortage of single-use N95 filtering facepiece respirators (FFRs). A combination of heat and humidity is a promising method for N95 FFR decontamination in crisis-capacity conditions; however, an understanding of its effect on viral inactivation and N95 respirator function is crucial to achieving effective decontamination. Objective: We reviewed the scientific literature on heat-based methods for decontamination of N95 FFRs contaminated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and viral analogues. We identified key parameters for SARS-CoV-2 bioburden reduction while preserving N95 fit and filtration, as well as methods that are likely ineffective. Key Findings: Viral inactivation by humid heat is highly sensitive to temperature, humidity, duration of exposure, and the local microenvironment (e.g., dried saliva). A process that achieves temperatures of 70-85°C and relative humidity >50% for at least 30 min is likely to inactivate SARS-CoV-2 (>3-log reduction) on N95 respirators while maintaining fit and filtration efficiency for three to five cycles. Dry heat is significantly less effective. Microwave-generated steam is another promising approach, although less studied, whereas 121°C autoclave treatments may damage some N95 FFRs. Humid heat will not inactivate all microorganisms, so reprocessed N95 respirators should be reused only by the original user. Conclusions: Effective bioburden reduction on N95 FFRs during the COVID-19 pandemic requires inactivation of SARS-CoV-2 and preservation of N95 fit and filtration. The literature suggests that humid heat protocols can achieve effective bioburden reduction. Proper industrial hygiene, biosafety controls, and clear protocols are required to reduce the risks of N95 reprocessing and reuse.

20.
Biosens Bioelectron ; 171: 112709, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075724

RESUMO

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was classified as a pandemic by the World Health Organization and has caused over 550,000 deaths worldwide as of July 2020. Accurate and scalable point-of-care devices would increase screening, diagnosis, and monitoring of COVID-19 patients. Here, we demonstrate rapid label-free electrochemical detection of SARS-CoV-2 antibodies using a commercially available impedance sensing platform. A 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS-CoV-2 monoclonal antibody CR3022 (0.1 µg/ml, 1.0 µg/ml, 10 µg/ml). Subsequent blinded testing was performed on six serum specimens taken from COVID-19 and non-COVID-19 patients (1:100 dilution factor). The platform was able to differentiate spikes in impedance measurements from a negative control (1% milk solution) for all CR3022 samples. Further, successful differentiation and detection of all positive clinical samples from negative control was achieved. Measured impedance values were consistent when compared to standard ELISA test results showing a strong correlation between them (R2=0.9). Detection occurs in less than five minutes and the well-based platform provides a simplified and familiar testing interface that can be readily adaptable for use in clinical settings.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Espectroscopia Dielétrica/instrumentação , Pneumonia Viral/sangue , Anticorpos Antivirais/imunologia , Técnicas Biossensoriais/economia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/economia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/economia , Infecções por Coronavirus/imunologia , Espectroscopia Dielétrica/economia , Impedância Elétrica , Desenho de Equipamento , Humanos , Proteínas Imobilizadas/imunologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , SARS-CoV-2 , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo
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