RESUMEN
The use of wearable sensors, such as inertial measurement units (IMUs), and machine learning for human intent recognition in health-related areas has grown considerably. However, there is limited research exploring how IMU quantity and placement affect human movement intent prediction (HMIP) at the joint level. The objective of this study was to analyze various combinations of IMU input signals to maximize the machine learning prediction accuracy for multiple simple movements. We trained a Random Forest algorithm to predict future joint angles across these movements using various sensor features. We hypothesized that joint angle prediction accuracy would increase with the addition of IMUs attached to adjacent body segments and that non-adjacent IMUs would not increase the prediction accuracy. The results indicated that the addition of adjacent IMUs to current joint angle inputs did not significantly increase the prediction accuracy (RMSE of 1.92° vs. 3.32° at the ankle, 8.78° vs. 12.54° at the knee, and 5.48° vs. 9.67° at the hip). Additionally, including non-adjacent IMUs did not increase the prediction accuracy (RMSE of 5.35° vs. 5.55° at the ankle, 20.29° vs. 20.71° at the knee, and 14.86° vs. 13.55° at the hip). These results demonstrated how future joint angle prediction during simple movements did not improve with the addition of IMUs alongside current joint angle inputs.
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Algoritmos , Aprendizaje Automático , Movimiento , Humanos , Movimiento/fisiología , Masculino , Adulto , Femenino , Dispositivos Electrónicos Vestibles , Adulto Joven , Rango del Movimiento Articular/fisiología , Fenómenos Biomecánicos/fisiología , Articulación de la Rodilla/fisiología , Articulaciones/fisiología , Articulación del Tobillo/fisiología , Articulación de la Cadera/fisiologíaRESUMEN
This study assesses the agreement of compressive and shear force estimates at the L5-S1 joint using inertial motion capture (IMC) within a musculoskeletal simulation model during manual lifting tasks, compared against a top-down optical motion capture (OMC)-based model. Thirty-six participants completed lifting and lowering tasks while wearing a modified Plug-in Gait marker set for the OMC and a full-body IMC set-up consisting of 17 sensors. The study focused on tasks with variable load weights, lifting heights, and trunk rotation angles. It was found that the IMC system consistently underestimated the compressive forces by an average of 34% (975.16 N) and the shear forces by 30% (291.77 N) compared with the OMC system. A critical observation was the discrepancy in joint angle measurements, particularly in trunk flexion, where the IMC-based model underestimated the angles by 10.92-11.19 degrees on average, with the extremes reaching up to 28 degrees. This underestimation was more pronounced in tasks involving greater flexion, notably impacting the force estimates. Additionally, this study highlights significant differences in the distance from the spine to the box during these tasks. On average, the IMC system showed an 8 cm shorter distance on the X axis and a 12-13 cm shorter distance on the Z axis during lifting and lowering, respectively, indicating a consistent underestimation of the segment length compared with the OMC system. These discrepancies in the joint angles and distances suggest potential limitations of the IMC system's sensor placement and model scaling. The load weight emerged as the most significant factor affecting force estimates, particularly at lower lifting heights, which involved more pronounced flexion movements. This study concludes that while the IMC system offers utility in ergonomic assessments, sensor placement and anthropometric modeling accuracy enhancements are imperative for more reliable force and kinematic estimations in occupational settings.
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Vértebras Lumbares , Captura de Movimiento , Humanos , Movimiento , Fenómenos Mecánicos , Fenómenos Biomecánicos , ElevaciónRESUMEN
Joint angles of the lower extremities have been calculated using gyroscope and accelerometer measurements from inertial measurement units (IMUs) without sensor drift by leveraging kinematic constraints. However, it is unknown whether these methods are generalizable to the upper extremity due to differences in motion dynamics. Furthermore, the extent that post-processed sensor fusion algorithms can improve measurement accuracy relative to more commonly used Kalman filter-based methods remains unknown. This study calculated the elbow and wrist joint angles of 13 participants performing a simple ≥30 min material transfer task at three rates (slow, medium, fast) using IMUs and kinematic constraints. The best-performing sensor fusion algorithm produced total root mean square errors (i.e., encompassing all three motion planes) of 6.6°, 3.6°, and 2.0° for the slow, medium, and fast transfer rates for the elbow and 2.2°, 1.7°, and 1.5° for the wrist, respectively.
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Articulación del Codo , Codo , Humanos , Muñeca , Extremidad Superior , Articulación de la MuñecaRESUMEN
During newborn lung injury, excessive activity of lysyl oxidases (LOXs) disrupts extracellular matrix (ECM) formation. Previous studies indicate that TGFß activation in the O2-injured mouse pup lung increases lysyl oxidase (LOX) expression. But how TGFß regulates this, and whether the LOXs generate excess pulmonary aldehydes are unknown. First, we determined that O2-mediated lung injury increases LOX protein expression in TGFß-stimulated pup lung interstitial fibroblasts. This regulation appeared to be direct; this is because TGFß treatment also increased LOX protein expression in isolated pup lung fibroblasts. Then using a fibroblast cell line, we determined that TGFß stimulates LOX expression at a transcriptional level via Smad2/3-dependent signaling. LOX is translated as a pro-protein that requires secretion and extracellular cleavage before assuming amine oxidase activity and, in some cells, reuptake with nuclear localization. We found that pro-LOX is processed in the newborn mouse pup lung. Also, O2-mediated injury was determined to increase pro-LOX secretion and nuclear LOX immunoreactivity particularly in areas populated with interstitial fibroblasts and exhibiting malformed ECM. Then, using molecular probes, we detected increased aldehyde levels in vivo in O2-injured pup lungs, which mapped to areas of increased pro-LOX secretion in lung sections. Increased activity of LOXs plays a critical role in the aldehyde generation; an inhibitor of LOXs prevented the elevation of aldehydes in the O2-injured pup lung. These results reveal new mechanisms of TGFß and LOX in newborn lung disease and suggest that aldehyde-reactive probes might have utility in sensing the activation of LOXs in vivo during lung injury.
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Aldehídos/metabolismo , Lesión Pulmonar/metabolismo , Pulmón/enzimología , Pulmón/patología , Proteína-Lisina 6-Oxidasa/metabolismo , Aldehídos/química , Animales , Animales Recién Nacidos , Embrión de Mamíferos/patología , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica , Ratones , Ratones Endogámicos C57BL , Sondas Moleculares/metabolismo , Células 3T3 NIH , Proteína-Lisina 6-Oxidasa/genética , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Transducción de Señal , Proteínas Smad/metabolismo , Transcripción Genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Electromyography (EMG) is commonly used to measure electrical activity of the skeletal muscles. As exoskeleton technology advances, these signals may be used to predict human intent for control purposes. This study used an artificial neural network trained and tested with knee flexion angles and knee muscle EMG signals to predict knee flexion angles during gait at 50, 100, 150, and 200 ms into the future. The hypothesis of this study was that the algorithm's prediction accuracy would only be affected by time into the future, not subject, gender or side, and that as time into the future increased, the prediction accuracy would decrease. A secondary hypothesis was that as the number of algorithm training trials increased, the prediction accuracy of the artificial neural network (ANN) would increase. The results of this study indicate that only time into the future affected the accuracy of knee flexion angle prediction (p < 0.001), whereby greater time resulted in reduced accuracy (0.68 to 4.62 degrees root mean square error (RMSE) from 50 to 200 ms). Additionally, increased number of training trials resulted in increased angle prediction accuracy.
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Articulación de la Rodilla , Rodilla , Electromiografía , Humanos , Aprendizaje Automático , Músculo EsqueléticoRESUMEN
Agricultural work is associated with increased risk of adverse musculoskeletal health outcomes. The purpose of this study was to quantify exposure to biomechanical factors among a sample (n = 55) of farmers in the Midwest region of the U.S. while they performed a variety of routine agricultural activities, and to compare exposure levels between these activities. Surface electromyography was used to estimate activity levels of the erector spinae, upper trapezius, forearm flexor, and forearm extensor muscle groups. Simultaneously, inertial sensors were used to measure kinematics of the trunk, upper arm, and wrist. In general, lower muscle activity levels, less extreme postures, and slower movement speeds were observed during activities that involved primarily the use of agricultural machinery in comparison to manual activities, suggesting a potential advantage of mechanization relative to musculoskeletal health. Median wrist movement speeds exceeding recently proposed exposure thresholds were also observed during many manual activities, such as milking animals and repairing equipment. Upper arm postures and movement speeds did not appear to confer excessive risk for shoulder-related outcomes (on the whole), but interpretation of the results is limited by a sampling approach that may not have captured the full extent of exposure variation. Not surprisingly, substantial variation in exposure levels were observed within each agricultural activity, which is related to substantial variation in the equipment, tools, and work practices used by participants. Ultimately, the results of this study contribute to an emerging literature in which the physical demands of routine agricultural work have been described on the basis of sensor-based measurements rather than more common self-report or observation-based approaches.
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Agricultura/estadística & datos numéricos , Sistema Musculoesquelético/patología , Exposición Profesional/estadística & datos numéricos , Fenómenos Biomecánicos , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/etiologíaRESUMEN
Ureteral stent (UrSt) placement has been shown to be a significant independent risk factor for BK viruria, viremia, and BK virus nephropathy. We assessed whether this observation could be validated at our high volume kidney transplant center that has had a strong historical focus on BK virus nephropathy detection. We performed a retrospective case-control study of adults receiving a kidney-only transplant and followed for 1 year between 2004 and 2011 with uniform immunosuppression and use of blood BK virus PCR screening protocol. Among 1147 patients, 443 (38.6%) received a UrSt and 17.2% with a UrSt had BK viremia versus 13.5% without stent (odds ratio 1.33; 95% CI: 1.00-1.78). We confirmed a previously reported association between immediate graft function (IGF) and higher rate of BK viremia (15.7% vs. 5.9% in patients without IGF). On multivariable competing risks Cox regression in patients with IGF, UrSt (adjusted hazard ratio [aHR] 1.35; 95% CI: 1.04-1.75) and African American race (aHR 1.47; 95% CI: 1.04-2.09) significantly increased the risk for BK viremia. In the largest sample size to date, we confirmed that UrSt placement during kidney transplant surgery is a risk factor for BK viremia within the first year post-transplant and that IGF is associated with BK viremia.
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Virus BK , Trasplante de Riñón/efectos adversos , Stents/efectos adversos , Cateterismo Urinario/efectos adversos , Viremia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Health information technology dashboards that integrate evidence-based quality indicators can efficiently and accurately display patient risk information to promote early intervention and improve overall quality of patient care. We describe the process of developing, evaluating, and implementing a dashboard designed to promote quality care through display of evidence-based quality indicators within an electronic health record. Clinician feedback was sought throughout the process. Usability evaluations were provided by three nurse pairs and one physician from medical-surgical areas. Task completion times, error rates, and ratings of system usability were collected to compare the use of quality indicators displayed on the dashboard to the indicators displayed in a conventional electronic health record across eight experimental scenarios. Participants rated the dashboard as "highly usable" following System Usability Scale (mean, 87.5 [SD, 9.6]) and Poststudy System Usability Questionnaire (mean, 1.7 [SD, 0.5]) criteria. Use of the dashboard led to reduced task completion times and error rates in comparison to the conventional electronic health record for quality indicator-related tasks. Clinician responses to the dashboard display capabilities were positive, and a multifaceted implementation plan has been used. Results suggest application of the dashboard in the care environment may lead to improved patient care.
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Presentación de Datos/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Informática Médica , Indicadores de Calidad de la Atención de Salud/estadística & datos numéricos , Práctica Clínica Basada en la Evidencia , Humanos , Errores Médicos/prevención & control , Indicadores de Calidad de la Atención de Salud/tendencias , Factores de Riesgo , Programas Informáticos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Fibrogenesis is the active production of extracellular matrix in response to tissue injury. In many chronic diseases persistent fibrogenesis results in the accumulation of scar tissue, which can lead to organ failure and death. However, no non-invasive technique exists to assess this key biological process. All tissue fibrogenesis results in the formation of allysine, which enables collagen cross-linking and leads to tissue stiffening and scar formation. We report herein a novel allysine-binding gadolinium chelate (GdOA), that can non-invasively detect and quantify the extent of fibrogenesis using magnetic resonance imaging (MRI). We demonstrate that GdOA signal enhancement correlates with the extent of the disease and is sensitive to a therapeutic response.
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Aminas/química , Quelantes/química , Imagen por Resonancia Magnética , Sondas Moleculares/química , Fibrosis Pulmonar/diagnóstico , Ácido 2-Aminoadípico/análogos & derivados , Ácido 2-Aminoadípico/química , Animales , Bleomicina , Gadolinio/química , Ratones , Conformación Molecular , Fibrosis Pulmonar/inducido químicamenteRESUMEN
Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6 weeks later. T2 weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T2 * maps of BAT were obtained at multiple time points before and after administration of the ß3 adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (51 ± 1 mm(3) versus 65 ± 3 mm(3) ; p < 0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p < 0.05). CL injection increased BAT T2 * in healthy animals but not in mice with heart failure (24 ± 4% versus 6 ± 2%; p < 0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright © 2016 John Wiley & Sons, Ltd.
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Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/patología , Técnicas de Imagen Cardíaca/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/metabolismo , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Tejido Adiposo Pardo/diagnóstico por imagen , Animales , Femenino , Insuficiencia Cardíaca/patología , Gotas Lipídicas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Oximetría/métodosRESUMEN
The accuracy and repeatability of an inertial measurement unit (IMU) system for directly measuring trunk angular displacement and upper arm elevation were evaluated over eight hours (i) in comparison to a gold standard, optical motion capture (OMC) system in a laboratory setting, and (ii) during a field-based assessment of dairy parlour work. Sample-to-sample root mean square differences between the IMU and OMC system ranged from 4.1° to 6.6° for the trunk and 7.2°-12.1° for the upper arm depending on the processing method. Estimates of mean angular displacement and angular displacement variation (difference between the 90th and 10th percentiles of angular displacement) were observed to change <4.5° on average in the laboratory and <1.5° on average in the field per eight hours of data collection. Results suggest the IMU system may serve as an acceptable instrument for directly measuring trunk and upper arm postures in field-based occupational exposure assessment studies with long sampling durations. Practitioner Summary: Few studies have evaluated inertial measurement unit (IMU) systems in the field or over long sampling durations. Results of this study indicate that the IMU system evaluated has reasonably good accuracy and repeatability for use in a field setting over a long sampling duration.
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Brazo , Industria Lechera , Movimiento/fisiología , Exposición Profesional , Torso , Adulto , Fenómenos Biomecánicos , Ergonomía , Humanos , Masculino , Postura , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented. METHODS AND RESULTS: Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells 3 weeks after coronary ligation. In half of the mice the donor and recipient strains were identical, and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to bone marrow mononuclear cell injection was seen in 1 mouse. The response of the majority of mice to bone marrow mononuclear cell injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology. CONCLUSIONS: Diffusion tensor magnetic resonance imaging tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.
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Trasplante de Médula Ósea/métodos , Imagen de Difusión Tensora/métodos , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Isquemia Miocárdica/patología , Isquemia Miocárdica/terapia , Animales , Anisotropía , Modelos Animales de Enfermedad , Voluntarios Sanos , Imagenología Tridimensional/métodos , Ratones , Ratones Endogámicos C57BL , Miocardio/patologíaRESUMEN
OBJECTIVES: Cell death in lymphatic organs, such as the spleen, is in part responsible for immunosuppression and contributes to mortality during sepsis. An early and noninvasive detection of lymphoid cell death could thus have significant clinical implications. Here, we tested in vivo imaging of lymphoid cell death using a near-infrared annexin V (AV-750). DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: C57BL/6J wild-type and toll-like receptor 3 knockout mice. INTERVENTIONS: Mild and severe polymicrobial sepsis was induced with cecum ligation and puncture. Serum cytokines and acute kidney injury markers were tested by immunoassay and quantitative reverse transcription-polymerase chain reaction, respectively. Sepsis-induced lymphoid cell death was detected by fluorescent AV-750 accumulation in the thorax and abdomen (in vivo), in isolated organs (ex vivo), and in isolated cells (flow cytometry). Caspase-3 cleavage/activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were tested for apoptosis. MEASUREMENTS AND MAIN RESULTS: Severe sepsis induced marked apoptosis in the thymus, spleen, and liver as demonstrated by cleaved caspase-3 and an increase in caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. A significant increase in fluorescent AV-750 signal was seen in the thoracic and upper abdominal fields and associated with the severity of sepsis. The in vivo thoracic and abdominal AV-750 fluorescent signal was attributed to the thymus, liver, and spleen as determined by ex vivo imaging and highly correlated with the levels of cell death in thymocytes and splenocytes, respectively, as measured by flow cytometry. Compared with wild-type septic mice, toll-like receptor 3 septic mice had attenuated abdominal AV-750 fluorescent signal, reduced ex vivo fluorescence in the spleen, and decreased splenocyte cell death. CONCLUSIONS: In vivo AV-750 fluorescent imaging provides spatially resolved and organ-specific detection of lymphoid cell death during polymicrobial sepsis. The AV-750 fluorescent intensity in the thoracic and abdominal fields is associated with sepsis severity and well correlated with sepsis-induced cell death in the thymus and spleen, respectively.
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Bacteriemia/microbiología , Muerte Celular , Coinfección/microbiología , Linfocitos/citología , Análisis de Varianza , Animales , Apoptosis/fisiología , Bacteriemia/fisiopatología , Western Blotting , Caspasa 3/metabolismo , Coinfección/diagnóstico , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Etiquetado Corte-Fin in Situ/métodos , Linfocitos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
Heat-induced radiolabeling (HIR) yielded (89) Zr-Feraheme (FH) nanoparticles (NPs) that were used to determine NP pharmacokinetics (PK) by positron emission tomography (PET). Standard uptake values indicated a fast hepatic uptake that corresponded to blood clearance, and a second, slow uptake process by lymph nodes and spleen. By cytometry, NPs were internalized by circulating monocytes and monocytes inâ vitro. Using an IV injection of HIR (89) Zr-FH (rather than inâ vitro cell labeling), PET/PK provided a view of monocyte trafficking, a key component of the immune response.
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Calor , Nanopartículas del Metal/química , Monocitos/citología , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Circonio/farmacocinética , Animales , Ratones , Radioisótopos/química , Radioisótopos/farmacocinética , Radiofármacos/química , Distribución Tisular , Circonio/químicaRESUMEN
Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause resulting in dyspnea and functional decline until death. There are currently no effective noninvasive tools to monitor disease progression and response to treatment. The objective of the present study was to determine whether molecular magnetic resonance imaging of the lung using a probe targeted to type I collagen could provide a direct, noninvasive method for assessment of pulmonary fibrosis in a mouse model. Pulmonary fibrosis was generated in mice by transtracheal instillation of bleomycin (BM). Six cohorts were imaged before and immediately after intravenous administration of molecular imaging probe: (1) BM plus collagen-targeted probe, EP-3533; (2) sham plus EP-3533; (3) BM plus nonbinding control probe, EP-3612; (4) sham plus EP-3612; (5) BM plus EP-3533 imaged early; and (6) BM plus EP-3533 imaged late. Signal-to-noise ratio (SNR) enhancement was quantified in the lungs and muscle. Lung tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. BM-treated mice had 35% higher lung collagen than sham mice (P < 0.0001). The SNR increase in the lungs of fibrotic mice after EP-3533 administration was twofold higher than in sham animals and twofold higher than in fibrotic or sham mice that received control probe, EP-3612 (P < 0.0001). The SNR increase in muscle was similar for all cohorts. For EP-3533, we observed a strong, positive, linear correlation between lung SNR increase and hydroxyproline levels (r = 0.72). Collagen-targeted probe EP-3533-enhanced magnetic resonance imaging specifically detects pulmonary fibrosis in a mouse model of disease.
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Imagen por Resonancia Magnética/métodos , Imagen Molecular/métodos , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/metabolismo , Animales , Bleomicina/toxicidad , Colágeno/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Técnicas de Sonda Molecular , Sondas Moleculares/administración & dosificación , Fibrosis Pulmonar/inducido químicamenteRESUMEN
High movement velocities are among the primary risk factors for work-related musculoskeletal disorders (MSDs). Ergonomists have commonly used two methods to calculate angular movement velocities of the upper arms using inertial measurement units (accelerometers and gyroscopes). Generalized velocity is the speed of movement traveled on the unit sphere per unit time. Inclination velocity is the derivative of the postural inclination angle relative to gravity with respect to time. Neither method captures the full extent of upper arm angular velocity. We propose a new method, the gyroscope vector magnitude (GVM), and demonstrate how GVM captures angular velocities around all motion axes and more accurately represents the true angular velocities of the upper arm. We use optical motion capture data to demonstrate that the previous methods for calculating angular velocities capture 89% and 77% relative to our proposed method.
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Brazo , Movimiento , Humanos , Movimiento (Física) , Fenómenos BiomecánicosRESUMEN
Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications. Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan. Design, Setting, and Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe. Main Outcomes and Measures: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure. Results: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients. Conclusions and Relevance: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.
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Oftalmopatías , Atrofia Geográfica , Humanos , Femenino , Anciano de 80 o más Años , Inyecciones Intravítreas , Aceites de Silicona/efectos adversos , Siliconas , Estudios Retrospectivos , Oftalmopatías/inducido químicamente , Retina , Atrofia Geográfica/inducido químicamenteRESUMEN
Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 µm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.