The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics.

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.

Defecatory Function Studies Using the Fecobionics Device Are Repeatable.

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.

Biomechanical constitutive modeling of the gastrointestinal tissues: a systematic review.

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.

Fecobionics Characterization of Patients With Fecal Incontinence.

Fecal incontinence (FI) is characterized by involuntary loss of rectal content. Up to 9.5% of Americans younger than 70 years suffer from FI.1 The pathophysiology has many causes and is not well understood and diagnosed.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

AIM: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. METHODS: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. RESULTS: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56). CONCLUSION: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Simulated stool for assessment of anorectal physiology.

Fecal continence is maintained by several mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, mobility, and psychological factors. The homeostatic balance is easily disturbed, resulting in symptoms including fecal incontinence and constipation. Current technologies for assessment of anorectal function have limitations. Overlap exist between data obtained in different patient groups, and there is lack of correlation between measurements and symptoms. This review describes a novel technology named Fecobionics for assessment of anorectal physiology. Fecobionics is a simulated stool, capable of dynamic measurements of a variety of variables during defecation in a single examination. The data facilitate novel analysis of defecatory function as well as providing the foundation for modeling studies of anorectal behavior. The advanced analysis can enhance our physiological understanding of defecation and future interdisciplinary research for unraveling defecatory function, anorectal sensory-motor disorders, and symptoms. This is a step in the direction of improved diagnosis of anorectal diseases.

Targeted polyethylenimine/(p53 plasmid) nanocomplexes for potential antitumor applications.

The development of the tumor-targeting ability of nanocarriers is of paramount importance for gene delivery into tumor lesions as well as to avoid biotoxicity. Here we report the synthesis of the polyethyleneimine-fluorescein isothiocyanate-folic acid (PEI-FITC-FA) polymer, which could condense the tumor suppressor pp53 to form nanocomplexes. These targeted nanocomplexes exhibited favorable physical properties including a small size of <100 nm, exploiting the enhanced permeability and retention effect and tumor-targeting ability by binding to the overexpressed FA receptors on tumor cell surfaces. In addition, once the nanocomplexes are accumulating in the tumor tissue, the target functional ligand, FA, can selectively recognize the over-expressed FA receptor and subsequently remain on the tumor cell surface, which can significantly promote the tumor cell uptake because of the time- and concentration-dependent internalization caused by the enhanced interaction between nanocomplex and tumor cell. Our results indicated that PEI-FITC-FA/pp53 nanocomplexes could be efficiently delivered into tumor cells, and subsequently induce tumor cell apoptosis. Thus, the targeted cationic polymer PEI-FITC-FA could be used as an advanced nanocarrier for gene delivery.

Amelioration of TMAO through probiotics and its potential role in atherosclerosis.

Atherosclerosis is a major cause of mortalities and morbidities worldwide. It is associated with hyperlipidemia and inflammation, and become chronic by triggering metabolites in different metabolic pathways. Disturbance in the human gut microbiota is now considered a critical factor in the atherosclerosis. Trimethylamine-N-oxide (TMAO) attracts attention and is regarded as a vital contributor in the development of atherosclerosis. TMAO is generated from its dietary precursors choline, carnitine, and phosphatidylcholine by gut microbiota into an intermediate compound known as trimethylamine (TMA), which is then oxidized into TMAO by hepatic flavin monooxygenases. The present review focus on advances in TMAO preventing strategies through probiotics, including, modulation of gut microbiome, metabolomics profile, miRNA, or probiotic antagonistic abilities. Furthermore, possible recommendations based on relevant literature have been presented, which could be applied in probiotics and atherosclerosis-preventing strategies.

Anal sphincter dysfunction in patients treated with primary radiotherapy for anal cancer: a study with the functional lumen imaging probe.

BACKGROUND: Sphincter-sparing radiotherapy or chemoradiation are standard treatments for patients with anal cancer. The ultimate treatment goal is full recovery from anal cancer with preserved anorectal function. Unfortunately, long-term survivors often suffer from severe anorectal symptoms. The aim of the present study was to characterize changes in anorectal physiology after radiotherapy for anal cancer. METHOD: We included 13 patients (10 women, age 63.4 ± 1.9) treated with radiotherapy or chemoradiation for anal cancer and 14 healthy volunteers (9 women, age 61.4 ± 1.5). Symptoms were assessed with scores for fecal incontinence and low anterior resection syndrome. Anorectal physiology was examined with anorectal manometry and the Functional Lumen Imaging Probe. RESULTS: Patients had a median Wexner fecal incontinence score of 5 (0-13) and a median LARS score of 29 (0-39). Compared to healthy volunteers, patients had lower mean (±SE) anal -resting (38 ± 5 vs. 71 ± 6, p < .001) and -squeeze pressures (76 ± 11 vs. 165 ± 15, p < .001). Patients also had lower anal yield pressure (15.5 ± 1.3 mmHg vs. 28.0 ± 2.0 mmHg, p < .001), higher distensibility, and lower resistance to flow (reduced resistance ratio of the anal canal during distension, q = 5.09, p < .001). No differences were found in median (range) rectal volumes at first sensation (70.5 (15-131) vs. 57 (18-132) ml, p > .4), urge (103 (54-176) vs. 90 (32-212), p > .6) or maximum tolerable volume (173 (86-413) vs. 119.5 (54-269) ml, p > .10). CONCLUSION: Patients treated with radiotherapy or chemoradiation for anal cancer have low anal resting and squeeze pressures as well as reduced resistance to distension and flow.

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

BACKGROUND: Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. AIMS: To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. METHODS: A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. RESULTS: Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). CONCLUSION: Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats.

Partial intestinal obstruction causes smooth muscle hypertrophy, enteric neuronal plasticity, motility disorders, and biomechanical remodeling. In this study we characterized the stimulus-response function of afferent fibers innervating the partially obstructed jejunum. A key question is whether changes in afferent firing arise from remodeled mechanical tissue properties or from adaptive afferent processes. Partial obstruction was created by placing a polyethylene ring for 2 wk in jejunum of seven rats. Sham obstruction was made in six rats and seven rats served as normal controls. Firing from mesenteric afferent nerve bundles was recorded during mechanical ramp, relaxation, and creep tests. Stress-strain, spike rate increase ratio (SRIR), and firing rate in single units were assessed for evaluation of interdependency of the mechanical stimulations, histomorphometry data, and afferent nerve discharge. Partial intestinal obstruction resulted in hypertrophy and jejunal stiffening proximal to the obstruction site. Low SRIR at low strains during fast distension and at high stresses during slow distension was found in the obstructed rats. Single unit analysis showed increased proportion of mechanosensitive units but absent high-threshold (HT) units during slow stimulation, decreased number of HT units during fast stimulation, and shift from HT sensitivity towards low threshold sensitivity in the obstructed jejunum. Biomechanical remodeling and altered afferent response to mechanical stimulations were found in the obstructed jejunum. Afferents from obstructed jejunum preserved their function in encoding ongoing mechanical stimulation but showed changes in their responsiveness. The findings support that mechanical factors rather than adaption are important for afferent remodeling.

Ravages of Diabetes on Gastrointestinal Sensory-Motor Function: Implications for Pathophysiology and Treatment.

Symptoms related to functional and sensory abnormalities are frequently encountered in patients with diabetes mellitus. Most symptoms are associated with impaired gastric and intestinal function. In this review, we discuss basic concepts of sensory-motor dysfunction and how they relate to clinical findings and gastrointestinal abnormalities that are commonly seen in diabetes. In addition, we review techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of sensory-motor function. Such technological advances, while not readily available in the clinical setting, may facilitate stratification and individualization of therapy in diabetic patients in the future. Unraveling the structural, mechanical, and sensory remodeling in diabetes disease is based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The final goal is to increase the understanding of the damage to GI structures and to sensory processing of symptoms, in order to assist clinicians with developing an optimal mechanics based treatment.

Distensibility and pain of the uterine cervix evaluated by novel techniques.

The article serves to review the literature on the human uterine cervix based on a new distension technology named functional luminal imaging probe. This technology was originally developed to study the biomechanical competence of the gastro-esophageal junction where it provides a geometric profile of the lumen during distension, which can be related to sensory data. We searched and reviewed publications on cervical distention from 2002. The functional luminal imaging probe technology has been used for studying the mechanical and mechano-sensory properties of the cervix in non-pregnant women. In early pregnant women and in term pregnant women, the technique provides geometric measurements from the whole cervical canal during distension, which changes dramatically during pregnancy. Furthermore, it has been demonstrated that the technique predicts the outcome of labor induction better than the Bishop score does. The functional luminal imaging probe technology has potential as a research tool as well as for clinical use in gynecology and obstetrics.

An image-based method to quantify biomechanical properties of the rectum in radiotherapy of prostate cancer.

BACKGROUND: Gastrointestinal morbidity after radiotherapy (RT) for prostate cancer may be related to the biomechanical properties of the rectum. In this study we present a magnetic resonance imaging (MRI)-based method to quantitate the thickness and elasticity of the rectal wall in prostate cancer patients treated with RT. MATERIAL AND METHODS: Four patients previously treated with RT for prostate cancer underwent an MRI session with stepwise rectal bag deflation (from a maximum tolerable volume to 0 ml, in 50 ml steps), with a probe inserted inside the bag to monitor the internal rectal pressure. MRIs were acquired using Dixon sequences (4 mm axial slice thickness) at each deflation step. Rectal walls were defined from the recto-sigmoid junction to 3 cm above the anal canal as the space between the inner and outer wall surfaces. The wall thickness was determined and biomechanical properties (strain and stress) were calculated from the pressure measurements and the MRI-segmented rectal walls. RESULTS: The integral rectal pressure varied for the maximum tolerable volume (range 150-250 ml) across patients and ranged from 1.3 to 4.0 kPa (SD = 1.2 kPa). Wall thickness was found to vary between patients and also across different rectum segments, with a mean (SD) thickness for the different segments at the 50 ml distension volume of 1.8-4.0 (0.6) mm. Stress showed larger variation than strain, with mean (SD) values for the different segments ranging between 1.5 and 7.0 (1.5) kPa. CONCLUSION: We have developed a method to quantify biomechanical properties of the rectal wall. The resulting rectal wall thickness, strain and stress differed between patients, as well as across different rectal wall sections. These findings could provide guidance in future predictive outcome modelling in order to better understand the rectal dose-volume response relationship.

Quantitative differences between primary and secondary peristaltic contractions of the esophagus.

BACKGROUND AND AIMS: Differences in contraction characteristics between primary and secondary peristalsis have only been scarcely studied. Recently new measures of contractile activity in the human esophagus were developed. The study aims were to use combined manometry and impedance planimetry [pressure-cross-sectional area (P-CSA)] recordings from healthy volunteers to examine esophageal peristalsis, and, furthermore, to investigate the effect of the motility enhancing drug erythromycin to study differential effects on the two types of contractions. METHODS: Sixteen healthy volunteers participated in the study [mean age 23 (range, 19-34) years, 6 females]. An esophageal probe with a bag for CSA measurement was positioned 10 cm above the lower esophageal sphincter. Bag volume was increased stepwise from 5 to 25 ml before and after intravenous infusion of 250 mg erythromycin. Swallow-evoked primary and distension-evoked secondary esophageal peristalsis were compared with regard to (1) pressure amplitude, (2) CSA amplitude, (3) preload tension (wall tension before an evoked contraction), (4) contractile tension, and (5) work outputs. RESULTS: Primary peristalsis induced more efficient contractions as the contraction amplitudes, work output and contractile tension were higher compared to secondary peristalsis (P < 0.001). Erythromycin induced change in CSA during distension-evoked secondary peristalsis (CSA before 212.9 ± 26.8 vs. after 180.5 ± 23.3, P < 0.05). The sensitivity to esophageal distension increased with the distending volume both before and during erythromycin. The sensitivity was not changed by erythromycin (P = 0.6). CONCLUSIONS: Esophageal primary peristaltic contractions were more forceful with longer duration, and higher work output compared to secondary peristalsis contractions. Erythromycin affected peristalsis only to a minor degree.

Pain evoked by distension of the uterine cervix in women with dysmenorrhea: evidence for central sensitization.

OBJECTIVE: To study sensitization in women with dysmenorrhea using a standardized experimental model. Women with dysmenorrhea experience intense visceral pain during menstruation. The dysmenorrhea pain mechanisms are not known but sensitization may play a role. DESIGN: Prospective experimental study. SAMPLE: Ten women with dysmenorrhea and 10 control women having uterine cervical distensions in the mid-follicular period (days 6-10). SETTING: University clinic. METHOD: Cervical distension was delivered as three phasic stimuli with 1 min between distensions and as a prolonged (1 min) distension. MAIN OUTCOME MEASURE: Sensory intensity rated on a continuous visual analog scale. RESULTS: Distension-induced pain was described as dull and aching and referred to the pelvis, lower back and lower abdomen. Larger evoked referred pain areas were present in women with dysmenorrhea compared with control women (p < 0.05). The pain threshold to the first stimulus was significantly higher in patients than controls (p < 0.04), but decreased significantly with repeated distensions (p < 0.01). For the prolonged distension the pain rating increased significantly (p < 0.008) in women with dysmenorrhea, but decreased (p < 0.02) in control women. CONCLUSIONS: Pain sensitization (temporal summation, i.e. increase in pain during prolonged stimulation, and facilitation of referred pain areas as an indicator of central nervous system changes) is present in women with dysmenorrhea. The study provided new information on a poorly understood yet widespread condition and a basis for clinical studies to develop a biomarker tests for objective assessment of dysmenorrhea.

Association between jejunal remodeling in fasting rats and hypersensitivity of intestinal afferent nerves to mechanical stimulation.

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.

BiU-net: A dual-branch structure based on two-stage fusion strategy for biomedical image segmentation.

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).

Consistency of Feces Affects Defecatory Function.

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.