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BACKGROUND AND OBJECTIVE: Computer-based biomedical image segmentation plays a crucial role in planning of assisted diagnostics and therapy. However, due to the variable size and irregular shape of the segmentation target, it is still a challenge to construct an effective medical image segmentation structure. Recently, hybrid architectures based on convolutional neural networks (CNNs) and transformers were proposed. However, most current backbones directly replace one or all convolutional layers with transformer blocks, regardless of the semantic gap between features. Thus, how to sufficiently and effectively eliminate the semantic gap as well as combine the global and local information is a critical challenge. METHODS: To address the challenge, we propose a novel structure, called BiU-Net, which integrates CNNs and transformers with a two-stage fusion strategy. In the first fusion stage, called Single-Scale Fusion (SSF) stage, the encoding layers of the CNNs and transformers are coupled, with both having the same feature map size. The SSF stage aims to reconstruct local features based on CNNs and long-range information based on transformers in each encoding block. In the second stage, Multi-Scale Fusion (MSF), BiU-Net interacts with multi-scale features from various encoding layers to eliminate the semantic gap between deep and shallow layers. Furthermore, a Context-Aware Block (CAB) is embedded in the bottleneck to reinforce multi-scale features in the decoder. RESULTS: Experiments on four public datasets were conducted. On the BUSI dataset, our BiU-Net achieved 85.50 % on Dice coefficient (Dice), 76.73 % on intersection over union (IoU), and 97.23 % on accuracy (ACC). Compared to the state-of-the-art method, BiU-Net improves Dice by 1.17 %. For the Monuseg dataset, the proposed method attained the highest scores, reaching 80.27 % and 67.22 % for Dice and IoU. The BiU-Net achieves 95.33 % and 81.22 % Dice on the PH2 and DRIVE datasets. CONCLUSIONS: The results of our experiments showed that BiU-Net transcends existing state-of-the-art methods on four publicly available biomedical datasets. Due to the powerful multi-scale feature extraction ability, our proposed BiU-Net is a versatile medical image segmentation framework for various types of medical images. The source code is released on (https://github.com/ZYLandy/BiU-Net).
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Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , AlgoritmosRESUMEN
Background/Aims: It is a common belief that constipated patients have hard feces that contributes to the difficulties defecating. To the best of our knowledge, no studies had been published on controlled evacuation of simulated feces with different consistencies. Methods: Twelve normal subjects were recruited for studies with the simulated feces device "Fecobionics" of different consistency (silicone shore 0A-40A corresponding to Bristol stool form scale types 2-4). The subjects filled out questionnaires and had the balloon expulsion test and anorectal manometry done for reference. The Fecobionics probes were inserted in rectum in random order with +20 minutes between insertions. The bag was filled to urge-to-defecate and evacuations took place in privacy. Non-parametric statistics with median and quartiles are provided. Results: One subject was excluded due to technical issues, and another had abnormal anorectal manometry-balloon expulsion test. The 4 females/6 males subjects were aged 23 (range 20-48) years. Most differences were observed between the 0A and 10A probe (duration, maximum bag pressure, duration x maximum bag pressure, and relaxation of the front pressure and the bend angle during evacuation), eg, the duration was 9 (8-12) seconds at 0A and 18 (12-21) seconds at 10A (P < 0.05), and maximum bag pressure was 107 (96-116) cmH2O at 0A and 140 (117-162) cmH2O at 10A (P < 0.05). The bend angle before evacuation differed between the probes whereas only the 10A differed from 40A during defecation. The 10A was harder to evacuate than the 0A probe. Except for the bend angles, no further significant change was observed from 10A to 40A. Conclusion: Fecal consistency affects defecatory parameters.
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Contractile patterns in rectum, puborectalis muscle and anal sphincter must be studied to understand defecation. Six subjects had contractile waveforms studied with Fecobionics. Symptom questionnaires, balloon expulsion test and anorectal manometry were done for reference. The Fecobionics bag was filled in rectum to urge-to-defecate volume and measurements were done for 4 h before the subjects attempted to evacuate the device. Pressures and bend angle (BA) variations were analyzed with Fast Fourier Transformation. Four normal subjects exhibited low frequency waves (< 0.06 Hz) for pressures and BA. The waves were uncoordinated between recordings, except for rear and bag pressures. Peak wave amplitudes occurred at 0.02-0.04 Hz. Pressures and the BA differed for peak 1 (p < 0.001) and peak 2 amplitudes (p < 0.005). The front pressure amplitude was bigger than the others (rear and BA, p < 0.05; bag, p < 0.005) for peak 1, and bigger than bag pressure (p < 0.005) and BA (p < 0.05) for peak 2. One subject was considered constipated with lower front pressure amplitudes compared to normal subjects and increased amplitudes for other parameters. The sixth subject was hyperreactive and differed from the other subjects. In conclusion, the rectum, anal sphincter and puborectalis muscle showed different contraction waves during prolonged measurements. The data call for larger studies to better understand normal defecation, feces-withholding patterns, and the implications on anorectal disorders.
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Canal Anal , Recto , Humanos , Recto/fisiología , Defecación/fisiología , Manometría , Estreñimiento , Contracción Muscular/fisiología , Diafragma Pélvico , HecesRESUMEN
Remodeling of Intestinal properties and hypersensitivity of intestinal afferents to mechanical stimulation were previously demonstrated in a fasting rat model. Other studies investigated the association between mechanical and histological remodeling during fasting. This study aimed to further explore the relationship between the jejunal remodeling and intestinal afferent hypersensitivity by combining afferent nerve recordings with histological and mechanical data. Eight male Sprague Dawley rats had no access to food for 7 days (Fasting group). Seven male rats served as controls (Control group). Jejunal segments were studied in vitro in an organ bath for analysis of afferent signaling and for analysis of mechanical and histomorphological parameters. Correlation analyses were done to analyze association between nerve activity (spike rate increase ratio, SRIR) at distension levels of 20, 40 and 80 cmH2O and mechanical stress and histomorphological changes of the jejunal segments. Compared with the Control group, the main findings in jejunal segments in the Fasting group were (1) Most histomorphometry parameters were reduced (P < 0.05-P < 0.001), (2) SRIR values were higher (P < 0.001), (3) The relative numbers of intermuscular and submucosal neurons were increased (P < 0.05-P < 0.01), and (4) SRIR was negatively correlated with intestinal wall thickness, circumferential muscle layer thickness and positively correlated with the inner residual strain, the number of neurons, and the mechanical stress. In conclusion, the fasting-induced histomorphological remodeling (reduced wall thickness and increased relative number of neurons) and biomechanical remodeling (residual strain changes and high stress level) of the intestine in fasting rats were associated with hypersensitivity of intestinal afferents. Afferent hypersensitivity appears to be dependent on stress rather than on strain.
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Intestinos , Yeyuno , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Fenómenos Biomecánicos , Yeyuno/inervación , Yeyuno/fisiología , AyunoRESUMEN
BACKGROUND: Only limited data exist on repeatability of anorectal studies with the established physiological and clinical technologies for assessment of anorectal function. Fecobionics is a new multi-sensor simulated feces that provide data by integrating elements from current tests. AIMS: To study repeatability of anorectal data obtained with the Fecobionics device. METHODS: We assessed the database of Fecobionics studies to determine how many repeated studies were done. From a total of 260 Fecobionics studies, 19 subjects with repeated studies using approximately the same protocol and prototype were identified. Key pressure and bending parameters were assessed and the repeatability analyzed using Bland Altman plots. Furthermore, the inter- and intra-individual coefficient of variation (CV) were computed. RESULTS: Fifteen subjects (5F/10 M) with repeated studies were normal subjects, three were patients with fecal incontinence and one subject suffered from chronic constipation. The main analysis was conducted on the cohort of normal subjects. The bias for 11 parameters were within the confidence interval, whereas two were slightly outside. The interindividual CV was lowest for the bend angle (10.1-10.7) and between 16.3 and 51.6 for the pressure parameters. The intra-individual CVs were approximately half of the inter-individual CVs, spanning from 9.7 to 27.6. CONCLUSION: All data from normal subjects were within previously defined normality. The Fecobionics data showed acceptable repeatability with bias within the confidence limits for almost all parameters. The intra-individual CV was much lower than the inter-individual CV. Dedicated large-scale studies are warranted to evaluate the influence of age, sex, and disease on repeatability as well as comparing between technologies.
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Estreñimiento , Incontinencia Fecal , Humanos , Estreñimiento/diagnóstico , Recto/fisiología , Incontinencia Fecal/diagnóstico , Heces , Canal Anal , Defecación/fisiología , Manometría/métodosRESUMEN
BACKGROUND: Stomach-related disorders impose medical challenges and are associated with significant social and economic costs. The field of biomechanics is promising for understanding tissue behavior and for development of medical treatments and surgical interventions. In gastroenterology, animal models are often used when studies on humans are not possible. Often large animal models with similar anatomical characteristics (size and shape) are preferred. However, it is uncertain if stomachs from humans and large animals have similar mechanical properties. The aim of the present study is to characterize and compare hyper- and viscoelastic properties of porcine and human gastric tissue using tension and radial compression tests. METHODS: Hyperelastic and viscoelastic properties were quantified from quasi-static ramp tests and stress relaxation tests. Tension in two directions and radial compression experiments were done on intact stomach wall samples as well as on separated mucosa and muscularis layer samples from porcine and human fundus, corpus and antrum. RESULTS AND CONCLUSIONS: Similar hyper- and viscoelastic constitutive models can be used to describe porcine and human gastric tissue. In total, 19 constitutive parameters were compared and results showed significant variations between species. For example, for intact circumferential samples from antrum, the stiffness (a) and relaxation (τ1) were greater for human samples than for porcine samples (p < 0.0001). The constitutive parameters were condition-, region- and layer-dependent and no distinct pattern hereof between species was found. This indicates that different parameters must be used to describe the specific situation. The present work provides insight into porcine and human gastric radial compressive and tensile hyper- and viscoelastic properties, strengthening the inter-species relation of the biomechanical properties. Constitutive relations were established that may aid development and translation of diagnostic or therapeutic devices with computational models.
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Estómago , Humanos , Porcinos , Animales , Elasticidad , Estrés Mecánico , Modelos Animales , Fenómenos BiomecánicosRESUMEN
Obesity has grown to epidemic proportions with 2.1 billion people being overweight worldwide. A food-grade expandable capsule named EndoXpand for the treatment of overweight people was designed and developed in this study. EndoXpand consists of an inner expandable material (core), an embracing membrane, and a gelatin capsule shell. It is designed to occupy volume in the stomach and reduce hunger sensation. The occupied volume is changeable over time, dependent on the number of ingested capsules and their degradation time. This will avoid gastric accommodation to constant volume devices as seen in the use of intragastric balloons. Several materials were tested. Collagen casing was selected as the membrane and corn silk was used to tie the membrane. Dried black fungus (Auricularia auricula) was the biological material that expanded most. However, synthesized cellulose-based hydrogel expanded more and was chosen as the optimal expandable core material. The hydrogel-based EndoXpand expanded 72 times after soaking in an acidic environment for 80 min. The corn silk ligations weakened and broke after 3 h. This resulted in release of the expanded material that was designed to easily pass the pylorus and travel down the intestine for digestion or excretion. In conclusion, this study provides design and in vitro proof-of-technology data for a potential groundbreaking approach. Further studies are needed in animal models and human phase I studies.
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Sobrepeso , Estómago , Animales , Humanos , Pérdida de Peso , Hidrogeles , SedaRESUMEN
The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are characterized by a biomechanical constitutive model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract. Here, a systematic review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies.
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Fecobionics is an integrated device that has shown promise for assessment of anorectal function. We used a wireless Fecobionics prototype to visualize defecatory patterns and to compute volume-pressure, contraction work, and flow. Twelve normal subjects were studied. The probe was 10 cm-long and contained pressure sensors and electrodes for impedance planimetry. Pressures, diameters, and volume data during defecation were analyzed. The bag was distended inside rectum to the urge-to-defecate level where after the subjects were asked to evacuate. The contraction work and defecatory flow were computed from the volume changes during expulsion. The minimum anal diameter during the evacuation was 17.6 ± 1.5 mm. The middle diameter recording was 10-20% lower than the front diameter channels and 10-20% bigger than the rear channels. The bag volume at urge correlated with the minimum diameter (r = 0.63). The diameter-pressure and volume-pressure loops were counterclockwise with phases of bag filling, isometric contraction, ejection and anal passage. The defecatory contraction work was 3520 ± 480 mL × cmH2O. The maximum flow during defecation was 302 ± 33 mL/s. The flow was associated with the anal diameter (r = 0.84) but not with the rectoanal pressure gradient (r = 0.14). Volume-pressure loops have a tremendous impact on the understanding of cardiopulmonary pathophysiology. Future studies will shed light on potential clinical impact in defecatory pathophysiology.
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Canal Anal , Defecación , Humanos , Defecación/fisiología , Manometría , Canal Anal/fisiología , Recto/fisiología , Contracción IsométricaRESUMEN
Strictures and abdominal pain often complicate Crohn's disease (CD). The primary aim was to explore whether parameters obtained by preoperative contrast-enhanced (CE) ultrasonography (US) and dynamic CE MR Enterography (DCE-MRE) of strictures associates with biomechanical properties. CD patients undergoing elective small intestinal surgery were preoperatively examined with DCE-MRE and CEUS. The excised intestine was distended utilizing a pressure bag. Luminal and outer bowel wall cross-sectional areas were measured with US. The circumferential stricture stiffness (Young's modulus E) was computed. Stiffness was associated with the initial slope of enhancement on DCE-MRE (ρ = 0.63, p = 0.007), reflecting active disease, but lacked association with CEUS parameters. For structural imaging parameters, inflammation and stricture stiffness were associated with prestenotic dilatation on US (τb = 0.43, p = 0.02) but not with MRE (τb = 0.01, p = 1.0). Strictures identified by US were stiffer, 16.8 (14.0-20.1) kPa, than those graded as no or uncertain strictures, 12.6 (10.5-15.1) kPa, p = 0.02. MRE global score (activity) was associated with E (ρ = 0.55, p = 0.018). Elastography did not correlate with circumferential stiffness. We conclude that increasing activity defined by the initial slope of enhancement on DCE-MRE and MRE global score were associated with stricture stiffness. Prestenotic dilatation on US could be a potential biomarker of CD small intestinal stricture stiffness.
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Several technologies have been developed for assessing anorectal function including the act of defecation. We used a new prototype of the Fecobionics technology, a multi-sensor simulated feces, to visualize defecatory patterns and introduced new metrics for anorectal physiology assessment in normal subjects. Fourteen subjects with normal fecal incontinence and constipation questionnaire scores were studied. The 10-cm-long Fecobionics device provided measurements of axial pressures, orientation, bending, and shape. The Fecobionics bag was distended to the urge-to-defecate level inside rectum where after the subjects were asked to evacuate. Physiological evacuation parameters were assessed. Special attention was paid to the Fecobionics rectoanal pressure gradient (F-RAPG) during evacuation. Anorectal manometry (ARM) and balloon expulsion test (BET) were done as references. The user interface displayed the fine coordination between pressures, orientation, bending angle, and shape. The pressures showed that Fecobionics was expelled in 11.5 s (quartiles 7.5 and 18.8s), which was shorter than the subjectively reported expulsion time of the BET balloon. Six subjects did not expel the BET balloon within 2 min. The F-RAPG was 101 (79-131) cmH2 O, whereas the ARM-RAPG was -28 (-5 to -47) cmH2 0 (p < 0.001). There was no association between the two RAPGs (r2 = 0.19). Fecobionics showed paradoxical contractions in one subject (7%) compared to 12 subjects with ARM (86%). Fecobionics obtained novel physiological data. Defecatory patterns and data are reported and can be used to guide larger-scale studies in normal subjects and patients with defecatory disorders. In accordance with other studies, this Fecobionics study questions the value of the ARM-RAPG.
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Canal Anal , Defecación , Canal Anal/fisiología , Defecación/fisiología , Estudios de Factibilidad , Humanos , Manometría/métodos , Recto/fisiologíaRESUMEN
Defecatory disorders including fecal incontinence (FI) are diagnosed on the symptom pattern supplemented by anorectal manometry (ARM), the balloon expulsion test (BET), and endo-anal ultrasonography. In this study, we used a simulated stool named Fecobionics to study distinct defecation patterns in FI patients using preload-afterload diagrams and to provide comparative data on defecation indices (DIs) between passive and urge incontinent patients. All subjects had Fecobionics, endo-anal ultrasonography and ARM-BET done. The Fecobionics bag was distended in rectum until urge in 37 female patients (64.1 ± 1.5 yrs) and a group of normal subjects (NS, 12F, age 64.8 ± 2.8 yrs). Rear-front pressure (preload-afterload) diagrams and DIs were compared between groups. The FISI score in the patients was 8.6 ± 0.6. The NS did not report FI-related symptoms. All patients and NS defecated Fecobionics and ARM-BET within 2 min. The urge volume was 46.1 ± 3.6 and 35.3 ± 5.9 mL in the FI and normal groups (P > 0.1). The expulsion duration was 14.8 ± 2.4 and 19.8 ± 5.1 s for the two groups (P > 0.1). The preload-afterload diagrams demonstrated clockwise loops that clearly differed between the FI subtypes and NS. The DIs showed profound difference between patients and NS. Fecobionics data showed higher correlation with symptoms in FI patients than ARM-BET. Fecobionics obtained novel pressure signatures in subtypes of FI patients and NS. Fecobionics provides DI data that cannot be obtained with ARM-BET.
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Incontinencia Fecal , Anciano , Canal Anal/diagnóstico por imagen , Defecación , Incontinencia Fecal/diagnóstico por imagen , Femenino , Humanos , Manometría , Persona de Mediana Edad , RectoRESUMEN
INTRODUCTION: Biofeedback therapy (BFT) is a well-known treatment for functional anorectal disorders. The effect of BFT was monitored in fecal incontinence (FI) patients with the Fecobionics test and with the conventional technologies, anorectal manometry (ARM) and balloon expulsion test (BET). METHODS: Studies were performed in 12 patients before and after 8 weeks of biofeedback training. The Fecal Incontinence Severity Index (FISI) score was obtained. Anal resting and squeeze pressures were measured before the bag was distended in the rectum until urge to defecate. Pressure recordings were made during Fecobionics evacuation. RESULTS: BFT resulted in 24% reduction in FISI scores (P < 0.01). Seven patients were characterized as responders. Anal pressures, the urge-to-defecate volume, and defecatory parameters did not change significantly during BFT. For ARM-BET, the maximum anal squeeze pressure, the urge-to-defecate volume, and the expulsion time were lower after BFT compared with those before BFT (P < 0.05). For Fecobionics, the change in urge volume (r = 0.74, P < 0.05) and the change in defecation index (r = 0.79, P < 0.01) were associated with the change in FISI score. None of the ARM-BET parameters were associated with the change in FISI score. It was studied whether any pre-BFT data could predict treatment success. The Fecobionics expulsion duration and the defecation index predicted the outcome (P < 0.05). The defecation index had a sensitivity of 100% and a specificity of 72%. None of the ARM-BET parameters predicted the outcome (all P > 0.2). DISCUSSION: Fecobionics was used as a tool to monitor the effect of BFT and proved better than conventional technologies for monitoring and predicting the outcome in the FISI score.
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Biorretroalimentación Psicológica , Incontinencia Fecal/terapia , Biorretroalimentación Psicológica/métodos , Defecación/fisiología , Incontinencia Fecal/diagnóstico , Humanos , Manometría/métodos , Índice de Severidad de la EnfermedadRESUMEN
Background: TET1 has been implicated in regulating inflammation and cardiovascular disease, but a newly discovered short isoform of TET1 (termed TET1s) exhibits higher expression in adult tissues than full-length TET1. However, the precise role of TET1 in cardiovascular disease remains undefined. Methods and Results: Based on TET1-/- knockout mice (with deletion of both TET1 and TET1s ) and TET1cs/cs mice (with deletion of only TET1), we found that TET1s deletion in TET1-/- mice resulted in more serious atherosclerotic lesions in the whole aorta than TET1cs/cs in the ApoE-/- background mice fed a high-fat diet. Atherosclerotic lesions with Oil red staining were dramatically localized in the aortic arch, abdominal aorta and ligated LCA, where they were exposed to OSS. Furthermore, the OSS-induced depression of TET1s in vitro and in vivo increased inflammatory cell and red blood cell infiltration into the subendothelial layer by impairing the vascular intimal barrier. TET1s upregulation enhanced vascular endothelial barrier function by increasing gap protein connexin 40 (CX40) expression as measured by RNA-seq and was confirmed by CX40 knockdown. TET1s interaction with Sin3a increased the global and CX40 promoter histone H3K27 acetylation levels, but not DNA methylation, to induce CX40 expression. Conclusions: These data demonstrate the unexpected discovery that laminar shear stress induces TET1s expression to protect the vascular endothelial barrier by increasing CX40 expression in ECs and that TET1s overexpression may be the core step for OSS-induced atherosclerosis therapy.
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Aterosclerosis , Enfermedades Cardiovasculares , Animales , Aorta/metabolismo , Aterosclerosis/metabolismo , Enfermedades Cardiovasculares/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Estrés MecánicoRESUMEN
BACKGROUND: Most patients who have undergone low anterior resection suffer from bowel dysfunction postoperatively. This condition is referred to as low anterior resection syndrome (LARS). The aim was to study defecatory patterns in LARS patients compared to a primary control group of fecal incontinence (FI) patients and normal subjects (NS) with the Fecobionics device. METHODS: Fecobionics expulsion parameters were assessed in an interventional study design. The Fecobionics probe contained pressure sensors at the front, rear, and inside the bag. The bag was distended until urge sensation in rectum in 11 LARS patients (5F/6M, 63.2 ± 2.9 years), 11 FI subjects (7F/4M, 64.4 ± 2.5 years), and 11 NS (7F/4M, 63.6 ± 3.0 years). Defecation indices were computed from the Fecobionics data. All subjects had high-resolution anorectal manometry (ARM) and balloon expulsion test (BET) done. Symptoms were evaluated with LARS and Wexner scores. KEY RESULTS: The LARS score in the LARS patients was 39.0 ± 0.6. The Wexner score in the LARS, FI, and NS groups was 14.2 ± 0.7, 10.1±1.0, and 0.0 ± 0.0 (p < 0.01). The resting anal pressure and squeeze pressure were lowest in LARS patients (p < 0.05). The urge volume was 11.8 ± 4.2, 59.6 ± 6.4, and 41.6 ± 6.4 ml in the LARS, FI, and NS groups, respectively (p < 0.001). The expulsion duration did not differ between groups. Defecation indices were lowest in the LARS patients (p < 0.05). ARM-BET confirmed the low urge volume in LARS patients whereas anal pressures did not differ between groups. CONCLUSIONS AND INFERENCES: The LARS patients had low anal pressures and urge volume. Most Defecation Indices differed between the LARS group and the other groups.
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Incontinencia Fecal , Enfermedades del Recto , Neoplasias del Recto , Canal Anal/cirugía , Defecación , Incontinencia Fecal/diagnóstico , Humanos , Manometría , Complicaciones Posoperatorias , Neoplasias del Recto/cirugía , Recto/cirugía , SíndromeRESUMEN
Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.
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Circulación Sanguínea/fisiología , Proteínas de Microfilamentos/fisiología , Proteínas Musculares/fisiología , Proteínas del Tejido Nervioso/fisiología , Proteínas de Pez Cebra/fisiología , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/fisiología , Animales , Animales Modificados Genéticamente , Capilares/metabolismo , Movimiento Celular , Células Endoteliales/metabolismo , Células Endoteliales/fisiología , Factores de Transcripción de Tipo Kruppel/genética , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Morfogénesis , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Pez Cebra/metabolismo , Pez Cebra/fisiología , Proteínas de Pez Cebra/metabolismoRESUMEN
BACKGROUND AND AIMS: Intestinal stenosis is a common complication of Crohn's Disease (CD). Stenosis is associated with alteration of bowel mechanical properties. This study aims to quantitate the mechanical properties of the intestinal stenosis and to explore associations between histology and mechanical remodeling at stenotic intestinal sites in CD patients. METHODS: Intestinal segments from stenotic sites were studied in vitro from 19 CD patients. A luminal catheter with a bag was used to stepwise pressurize the intestinal segments from 0-100 cmH2O with 10 cmH2O increments. B-mode ultrasound images were obtained at the narrowest part of the stenosis at each pressure level and morphometric parameters were obtained from ultrasound images. The mechanical behavior of the stenotic tissue were characterized by using an isotropic three dimensional strain energy function in Demiray model form, the mechanical constants were obtained by fitting the model to the recorded intraluminal pressure and the inner radius of the stenotic segment of the small bowel. Grading scores were used for histological analysis of inflammation, fibrosis, muscular hypertrophy and adipocyte proliferation in the intestinal layers. The collagen area fraction in intestinal layers was also calculated. Associations between histological and the mechanical constants (stiffness) were analyzed. RESULTS: Chronic inflammation was mainly located in mucosa whereas fibrosis was found in submucosa. The mechanical remodeling was performed with changed mechanical constants ranged between 0.35-13.68kPa. The mechanical properties changes were associated mainly with chronic inflammation, fibrosis and combination of inflammation and fibrosis (R>0.69, P<0.001). Furthermore, the mechanical properties correlated with the collagen fraction in submucosa and muscular layers (R>0.53, P<0.05). CONCLUSIONS: We quantitated the intestinal stenosis stiffness. Associations were found between bowel mechanical remodeling and histological changes at the stenotic site in CD patients. STATEMENT OF SIGNIFICANCE: Although intestinal ultrasonography, CT and MRI can be used to diagnose Crohn's Disease (CD)-associated bowel strictures, these techniques may not have sufficient accuracy and resolution to differentiate predominantly inflammatory strictures from predominantly fibrotic strictures. The present study aims to quantitate the mechanical remodeling of intestinal stenosis and to explore the associations between histological parameters and mechanical properties at the intestinal stenotic sites in CD patients. For the first time, we quantitatively demonstrated that the mechanical properties of the intestinal wall in CD stenosis are associated with the chronic inflammation, fibrosis and collagen fraction in the intestinal layers. The results of this study may facilitate design and development of artificial biomaterials for gastrointestinal organs. The potential clinical implication of this study is that the histological characteristics in patients with CD can be predicted clinically by means of inflammation and fibrosis assessment in conjunction with tissue stiffness measurement.