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Neutrophil elastase (HNE), like other members of the so-called GASPIDs (Granule-Associated Serine Peptidases of Immune Defense), is activated during protein biosynthesis in myeloid precursors and stored enzymatically active in cytoplasmic granules of resting neutrophils until secreted at sites of host defense and inflammation. Inhibitors thus could bind to the fully formed active site of the protease intracellularly in immature progenitors, in circulating neutrophils, or to HNE secreted into the extracellular space. Here, we have compared the ability of a panel of diverse inhibitors to inhibit HNE in the U937 progenitor cell line, in human blood-derived neutrophils, and in solution. Most synthetic inhibitors and, surprisingly, even a small naturally occurring proteinaceous inhibitor inhibit HNE intracellularly, but the extent and dynamics differ markedly from classical enzyme kinetics describing extracellular inhibition. Intracellular inhibition of HNE potentially affects neutrophil functions and has side effects, but it avoids competition of inhibitors with extracellular substrates that limit its efficacy. As both intra- and extracellular inhibition have advantages and disadvantages, the quantification of intracellular inhibition, in addition to classical enzyme kinetics, will aid the design of novel, clinically applicable HNE inhibitors with targeted sites of action.
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Elastasa de Leucocito , Neutrófilos , Humanos , Elastasa de Leucocito/metabolismo , Elastasa de Leucocito/antagonistas & inhibidores , Neutrófilos/metabolismo , Neutrófilos/enzimología , Cinética , Células U937 , Espacio Extracelular/enzimología , Inhibidores de Serina Proteinasa/farmacologíaRESUMEN
Rectus sheath blocks can provide analgesia for upper abdominal midline incisions. These blocks can be placed on patients who are anticoagulated, supine, and under general anesthesia. However, block success rates remain low, presumably because of the difficulty of placing local anesthetic between the correct fascial layers. Here we characterize a hypoechoic triangle with sonography, an anatomic space between adjacent rectus abdominis segments that can be accessed for easier needle tip and catheter placement. This approach could reduce reliance on hydrodissection to correctly identify the potential space and instead improve block efficacy by offering providers a discrete target for local anesthesia.
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Bloqueo Nervioso , Ultrasonografía Intervencional , Humanos , Ultrasonografía , Anestésicos Locales , Recto del Abdomen/diagnóstico por imagenRESUMEN
In cardiac cine magnetic resonance imaging (MRI), the heart is repeatedly imaged at numerous time points during the cardiac cycle. Frequently, the temporal evolution of a certain region of interest such as the ventricles or the atria is highly relevant for clinical diagnosis. In this paper, we devise a novel approach that allows for an automatized propagation of an arbitrary region of interest (ROI) along the cardiac cycle from respective annotated ROIs provided by medical experts at two different points in time, most frequently at the end-systolic (ES) and the end-diastolic (ED) cardiac phases. At its core, a 3D TV- L1 -based optical flow algorithm computes the apparent motion of consecutive MRI images in forward and backward directions. Subsequently, the given terminal annotated masks are propagated by this bidirectional optical flow in 3D, which results, however, in improper initial estimates of the segmentation masks due to numerical inaccuracies. These initially propagated segmentation masks are then refined by a 3D U-Net-based convolutional neural network (CNN), which was trained to enforce consistency with the forward and backward warped masks using a novel loss function. Moreover, a penalization term in the loss function controls large deviations from the initial segmentation masks. This method is benchmarked both on a new dataset with annotated single ventricles containing patients with severe heart diseases and on a publicly available dataset with different annotated ROIs. We emphasize that our novel loss function enables fine-tuning the CNN on a single patient, thereby yielding state-of-the-art results along the complete cardiac cycle.
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Imagen por Resonancia Cinemagnética , Flujo Optico , Humanos , Imagen por Resonancia Cinemagnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Corazón/diagnóstico por imagen , Ventrículos Cardíacos , Imagen por Resonancia Magnética/métodos , Atrios CardíacosRESUMEN
Microbial communities reside at the interface between humans and their environment. Whether the microbiome can be leveraged to gain information on human interaction with museum objects is unclear. To investigate this, we selected objects from the Museum für Naturkunde and the Pergamonmuseum in Berlin, Germany, varying in material and size. Using swabs, we collected 126 samples from natural and cultural heritage objects, which were analyzed through 16S rRNA sequencing. By comparing the microbial composition of touched and untouched objects, we identified a microbial signature associated with human skin microbes. Applying this signature to cultural heritage objects, we identified areas with varying degrees of exposure to human contact on the Ishtar gate and Sam'al gate lions. Furthermore, we differentiated objects touched by two different individuals. Our findings demonstrate that the microbiome of museum objects provides insights into the level of human contact, crucial for conservation, heritage science, and potentially provenance research.
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INTRODUCTION: Although Checklists (CL) for routine anesthesia cases have demonstrated their values in various studies, they have found little traction so far. While several reports have shown the benefit of CL preventing omissions prior to anesthesia induction, no investigation yet has scrutinized omissions during the post-induction phase immediately after intubation. This study evaluated the rate of omissions prior to and following the induction of non-emergent general anesthesia, as well as the impact of checklists on omission prevention. METHODS: We performed a monocentric, prospective, observational study during induction of general anesthesia cases. We evaluated the omission rate made for the pre- as well as the immediate post-induction phase and determined the impact of pre-and post-induction CL on the rate of omission corrections. The CL used were introduced two years prior to the study. The observed providers were limited to those familiar with the institutional CL. Usage of CL was not mandated. RESULTS: 237 general anesthesia inductions were included in the observation. At least one omission in 32% of all cases in the pre-induction setup was found and in 40% within the immediate post-induction phases. CL significantly reduced omission rates (relative risk = 0.64, 95% CI = 0.45-0.92, p = 0.01). CONCLUSION: Omission rates during the pre- and post-induction phases of routine general anesthesia procedures remain high. Pre- and post-induction CL have the potential to increase patient safety and should be considered for routine anesthesia with appropriate training provided.
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Anestesiología , Internado y Residencia , Humanos , Lista de Verificación , Estudios Prospectivos , Anestesia General , Anestesiología/educaciónRESUMEN
Heart rate (HR) responses to maximal exercise are commonly used for the prescription of training intensities in pulmonary rehabilitation. Those intensities are usually based on fixed percentages of peak HR (HRpeak), heart rate reserve (HRR), or peak work load (Wpeak), and rarely on HRs at the individual ventilatory thresholds (VT1 and VT2) derived from cardiopulmonary exercise testing (CPET). For patients suffering from interstitial lung disease (ILD), data on cardiorespiratory responses to CPET are scarce. Thus, the aim of this study was to record cardiorespiratory responses to CPET and to compare fixed HR percentages with HRs at VT1 and VT2 in ILD patients. A total of 120 subjects, 80 ILD patients and 40 healthy controls, underwent a symptom-limited CPET. From the ILD patient, 32 suffered from idiopathic pulmonary fibrosis (IPF), 37 from connective tissue disease (CTD), and 11 from sarcoidosis. HRs at fixed percentages, that is, at 70%HRpeak, at 70%Wpeak, and at 60%HRR were significantly lower in the ILD patients compared with the control group (p-values: 0.001, 0.044, and 0.011). Large percentages of HR values at 70%Wpeak and 60%HRR ranged between the HRs at VT1 and VT2 in ILD subgroups and controls as well. HRs at 70%HRpeak were lower than HRs at VT1 in 66% of the IPF patients, 54% of the CTD patients, and 55% of patients with sarcoidosis compared with 18% in the control group. Our findings demonstrate a considerable scattering of fixed HR percentages compared with HRs at the individual VTs derived from CPET in ILD patients. These findings may provide valuable information for the prescription of exercise intensity in pulmonary rehabilitation of ILD patients.
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Enfermedades del Tejido Conjuntivo , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Prueba de Esfuerzo , Frecuencia Cardíaca , HumanosRESUMEN
Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment. Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3-6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50). Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO2 peak - % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO2 peak; p = 0.013 and VT2/VO2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R 2) of the variance in relative VO2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO2 peak, which were related to higher relative VO2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV. Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3-6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO2 peak in those patients, which may have important implications on rehabilitation programs.
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This Research Article describes a novel method for removal of particulate contamination, loosely referred to as dust, from solid surfaces using polymeric micropillars. In this Research Article, we illustrate for the first time that polymeric microfibrils of controlled interfacial and geometrical properties can effectively remove micrometric and submicrometric contaminant particles from a solid surface without damaging the underlying substrate. Once these microfibrils are brought into contact with a contaminated surface, because of their their soft and flexible structure, they develop intimate contact with both the surface contaminants and the substrate. While these intrinsically nonsticky micropillars have minimal interfacial interactions with the substrate, we show that they produce strong interfacial interactions with the contaminant particles, granting the detachment of the particles from the surface upon retraction of the cleaning material. The origin and strength of the interfacial interactions at the interfaces between a contaminant particle and both the substrate and the cleaning materials are thoroughly discussed. Unlike flat substrates of the same material, using microfibrillar structures of controlled interfacial and geometrical properties also allows the elimination of the adsorbed particles from the contact interface. Here we demonstrate that by moving the adsorbed particles from the tip to the side of the fibrils and consequently removing them from the contact interface, polymeric microfibrils can clean all contaminant particles from the surface. The effects of the geometrical and interfacial properties of polymeric micropillars on removing the adsorbed particles from the tips of the pillars are fully discussed. This research is not only important in terms of introducing a novel method which can offer a new paradigm for thorough yet nondestructive cleaning of dust particles from solid surfaces, but also it is of fundamental significance for researchers with interests in exploiting the benefits offered by microstructured surfaces in development of interfacially active materials and devices.
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We compared the cardiac output measured by the transpulmonary aortic single indicator thermodilution method with that by the pulmonary artery catheterization in a patient with ventricular septal rupture after acute myocardial infarction. Though the former cardiac output was lower than the latter, in the presence of the ventricular septal rupture, the cardiac outputs were equal after the rupture was closed. This indicates that, while the cardiac output measured by the pulmonary artery catheter is influenced by the ventricular left-to-right shunt, transpulmonary aortic thermodilution method measures the true cardiac output of the left heart, which is responsible for organ perfusion.