Rectal Region Research Articles

Aberrant expression of miR-143/miR-223/miR4478 and miR145 as prognostic factor for colorectal cancer patients

Colorectal cancer (CRC) is a type of malignancy that develops in the colon or rectal region. It develops due to abnormal growth and proliferation of cells in the lining of the colon, forming a tumor. This study included tissue samples (56 malignant and 56 matched normal samples). miRNAs were determined and retrieved from miRBase database and moderated by p53 gene. Expression levels of miRNA were varied. Only miR-223 revealed greater expression than normal matched tissue. mMiR-143, miR-4478, and miR-145 exhibited lower expression than matched normal tissue. Only miR-143 and miR-145 showed considerable variations in the expression among groups while miR-4478 did not demonstrate statistically substantial difference. In conclusion, this study highlights that upregulation of P53 and miR-223 and downregulation of miR-145 and miR-143 were associated with cancer advancement and unfavorable prognosis in Saudi CRC patients, indicating P53, miR-223, miR-145 and miR-143 to be novel and valuable signatures for predicting the outcomes for patients with CRC.

Associations of intestinal diseases with anal diseases: a Mendelian randomization study

Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn’s disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

Utility of facial thermography in the recognition of acute pain in hospitalized cats (Felis catus)

Different clinical conditions have been associated with the presence of pain in animals, so understanding the pathophysiological changes associated with their response is essential in in-hospital clinical monitoring. The objective of this study was to describe the usefulness of facial thermography in the recognition of acute pain in hospitalized cats (Felis catus), for which 71 cats were studied with an average weight of 4.3±1.4 Kg and an age average of 4.4±3.5 years. Facial temperature values were obtained in different region of interest (ROI) and compared according to the values of the Grimace pain scale in cats according to the following subclassification: Group 1, control animals (n=10); Group 2, animals classified with score 0-3 (n=21); Group 3, animals classified with score 4-6 (n=30) and Group 4, animals classified with score 7-10 (n=10). The global average temperature of the facial (F), auricular (A), periocular (PO), nasal (N) and rectal (R) regions was 33.7±1.9; 31.4±3.6; 32.1±0.9; 28.9±4.5 and 38.3±0.8 oC respectively. A difference (p<0.05) was observed between the temperature of A and PO as well as between PO and N, but not between A and N. The present study allowed us to show an increase (p=0.0484) in the temperature mean PO ROI in G4 animals compared to G1 and a correlation with R temperature and peak temperature in the PO region in all groups. It is concluded that the increase in temperature of the periocular region and the nasal plane observed through infrared thermal imaging of the facial surface of hospitalized cats suggests the presence of clinically relevant acute pain. Facial thermography is a safe and non-invasive diagnostic method that complements other methods of identifying pain in cats.

Anal fistulas at roof of ischiorectal fossa inside levator ani muscle (RIFIL): MRIs key role their management

Fistulas pathways in the anal and rectal region are tricky to delimit and define their extension using imaging (MRI) because of the multilayer and condense anatomy of this region. Recently, with the increased clarity that MRIs brought to this pathology

Beyond boundaries: Feasibility of curved linear array echoendoscope in appendiceal neoplasm detection

We recently read with great interest a study by Zhang et al in the World Journal of Gastroenterology . In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with endoscopic ultrasound (EUS) using different scopes. AMNs are rare neoplastic lesions characterized by an accumulation of mucin inside a cystic dilatation of the appendix. Clinically, they can present as nonspecific acute appendicitis. AMNs can turn into a life-threatening condition, termed pseudomyxoma peritonei, in which the ruptured appendix causes accumulation of mucin in the abdomen. Therefore, accurate and rapid diagnosis of AMN is essential. EUS is able to confirm and stage AMNs; although, EUS examination was once limited to the rectal and anal regions due to the conventional oblique-view scopes. With the emergence of new forward-view linear echoendoscopes and instruments like EUS miniprobes and overtubes, the scope of examination is changing. Herein, we discuss the feasibility of using the curved linear array echoendoscopes to examine cecal and appendiceal orifice lesions.

A REVIEW ON MANAGEMENT PRINCIPLES OF ARSHA (HAEMORRHOIDS) AS PER ACHARAYA CHARAKA

Arshas (Haemorrhoids) is one of the ano rectal diseases that affects Gudapradesha (ano rectal region), Arsh is also mentioned in Astha Mahagada (8 Major disorders). haemorrhoid is one of the most prevalent illnesses that significantly lowers living quality of life. Many people in the world are suffering from this disease, this illness can strike any age group and affect both men and women. The primary causes of piles are unusual diet (junk food, lack of fibre diet and more intake spicy food) and lifestyle (inactive occupation and lack of exercise). Mental stress may potentially be the cause of Arsha. Many treatment modalities of Arsh have been told by Acharyas like Surgical, Para-Surgical and Conservatives. Acharya Shusruta explains four measures in the therapeutic plan: Bheshaja Chikitsa (Medication), Kshara karma (Chemical cautery), Agni karma (Thermal cauterization), and Shastra chikitsa (Surgery). Sushrua has described these four methods in detail, Sushruta's main treatise on surgery: That’s why he has laid special emphasis on surgery. Acharya charaka explained the conservative management (Bheshaja chikitsa) of haemorrhoids in detail in Chikitsa sthan chapter 14. In this article we will describe in detail the treatment given by Acharya Charak.

The effect of the re-segmentation method on improving the performance of rectal cancer image segmentation models.

Rapid and accurate segmentation of tumor regions from rectal cancer images can better understand the patientâs lesions and surrounding tissues, providing more effective auxiliary diagnostic information. However, cutting rectal tumors with deep learning still cannot be compared with manual segmentation, and a major obstacle to cutting rectal tumors with deep learning is the lack of high-quality data sets. We propose to use our Re-segmentation Method to manually correct the model segmentation area and put it into training and training ideas. The data set has been made publicly available. Methods: A total of 354 rectal cancer CT images and 308 rectal region images labeled by experts from Jiangxi Cancer Hospital were included in the data set. Six network architectures are used to train the data set, and the region predicted by the model is manually revised and then put into training to improve the ability of model segmentation and then perform performance measurement. In this study, we use the Resegmentation Method for various popular network architectures. By comparing the evaluation indicators before and after using the Re-segmentation Method, we prove that our proposed Re-segmentation Method can further improve the performance of the rectal cancer image segmentation model.

Comparison of Candida colonization in intensive care unit patients with and without COVID-19: First prospective cohort study from Turkey.

Candida species are the primary cause of fungal infections in intensive care units (ICUs). Despite the increasing prevalence of Candida-related infections, monitoring the progression of these infections from colonization in COVID-19 ICU patients lacks sufficient information. This study aims prospectively to compare 62 COVID-19 and 60 non-COVID-19 ICU patients from admission to discharge in terms of colonization development, rates, isolated Candida species, risk factors, and Candida infections during hospitalization. A total of 1464 samples were collected at specific time intervals from various body sites [mouth, skin (axilla), rectal, and urine]. All samples were inoculated onto CHROMagar Candida and CHROMagar Candida Plus media, and isolates identified using MALDI-TOF MS. COVID-19 patients exhibited significantly higher colonization rates in oral, rectal, and urine samples compared to non-COVID-19 patients, (p<0.05). Among the Candida species, non-albicans Candida was more frequently detected in COVID-19 patients, particularly in oral (75.8%-25%; p<0.001) and rectal regions (74.19% - 46.66%; p<0.05). Colonization with mixed Candida species was also more prevalent in the oropharyngeal region (p<0.05). Mechanical ventilation and corticosteroid use emerged as elevated risk factors among COVID-19 patients (p<0.05). Despite the colonization prevalence, both COVID-19-positive and negative patients exhibited low incidences of Candida infections, with rates of 9.67% (n=6/62) and 6.67% (n=3/60), respectively. Consequently, although Candida colonization rates were higher in COVID-19 ICU patients, there was no significant difference in Candida infection development compared to the non-COVID-19 group. However, the elevated rate of non-albicans Candida isolates highlights potential future infections, particularly given their intrinsic resistance in prophylactic or empirical treatments if needed. Additionally, the high rate of mixed colonization emphasizes the importance of using chromogenic media for routine evaluation.

Cell Spatial Analysis in Crohn's Disease: Unveiling Local Cell Arrangement Pattern with Graph-based Signatures.

Crohn's disease (CD) is a chronic and relapsing inflammatory condition that affects segments of the gastrointestinal tract. CD activity is determined by histological findings, particularly the density of neutrophils observed on Hematoxylin and Eosin stains (H&E) imaging. However, understanding the broader morphometry and local cell arrangement beyond cell counting and tissue morphology remains challenging. To address this, we characterize six distinct cell types from H&E images and develop a novel approach for the local spatial signature of each cell. Specifically, we create a 10-cell neighborhood matrix, representing neighboring cell arrangements for each individual cell. Utilizing t-SNE for non-linear spatial projection in scatter-plot and Kernel Density Estimation contour-plot formats, our study examines patterns of differences in the cellular environment associated with the odds ratio of spatial patterns between active CD and control groups. This analysis is based on data collected at the two research institutes. The findings reveal heterogeneous nearest-neighbor patterns, signifying distinct tendencies of cell clustering, with a particular focus on the rectum region. These variations underscore the impact of data heterogeneity on cell spatial arrangements in CD patients. Moreover, the spatial distribution disparities between the two research sites highlight the significance of collaborative efforts among healthcare organizations. All research analysis pipeline tools are available at https://github.com/MASILab/cellNN.

A Case Study on Effective Management of Arsha (II Degree Haemorrhoids) by Teekshna Kshar Pratisarana

Arsha, commonly known as haemorrhoids, is a prevalent medical condition characterized by dilated blood vessels in ano rectal region and they can cause bleeding, pain, mucous discharge, discomfort etc. The primary causes of Arsha include increased pressure on the rectal veins, commonly attributed to chronic constipation, prolonged sitting, and straining during bowel movements. Genetic predisposition and certain lifestyle factors, such as a sedentary lifestyle and low fiber diet, can also contribute to the development of haemorrhoids. Arsha requires a surgical technique in modern treatment, such as haemorrhoidectomy, rubber band ligation, and so on, but after sometime of excision there is great possibility of reappearance of the disease. But in Ayurveda, fourfold management of Arsha has been indicated viz., Bheshaja, Kshar karma, Agni karma and Shastra karma according to chronicity and presentation of the disease. In this case study, a 40 years old female patient presented with complaints of some mass coming out during defecation, bleeding, pain and mucous discharge while passing stool to the Shalya OPD, Rishikul Campus, Uttarakhand Ayurved University Haridwar. The patient was treated successfully with Kshar karma application. The pile mass, per rectal haemorrhage and mucous discharge was gone in 7 days and the patient was free of all symptoms within 15 days. The findings revealed that there are maximum advantages which are shared in this case study.

P183 Therapeutic Effects of Curcumin and Ginsenoside Combination in a Animal Model of Radiation Proctitis

Abstract Background Although various preventive and therapeutic modalities have been proposed to manage radiation-induced proctitis, there are no universally accepted preventive measures for effective treatment. This study aimed to investigate using an animal model whether the combination of curcumin and ginsenoside could be an effective treatment or preventive agent for progressive rectal inflammation caused by radiation. Methods C57BL/6 mice were exposed to gamma irradiation at 27 Gy (3 Gy/min) in the lower abdominal (rectal) region, establishing an animal model with acute radiation proctitis. A combination hydrogel containing 5 mM curcumin and 1 mM ginsenoside Rh1 was prepared and administered into the inflammed rectum of the murine model. This administration was repeated every 2 to 3 days after radiation exposure for a total of 6 times. Two weeks after radiation exposure, the mice were sacrificed to obtain the irradiated tissue samples. The histological and molecular evaluations were performed using H&amp;E staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, Proliferating Cell Nuclear Antigen (PCNA) staining, immunohistochemistry, and qPCR. Results The murine group treated with the combination hydrogel of curcumin and ginsenoside showed significant restoration of the damaged rectal mucosa induced by radiation, including recovery of the mucosal layer and villi, mitigation of epithelial loss, and repair of crypt damage, compared to control group. Additionally, at the cellular level, a comparative analysis of apoptosis and proliferation within the tissues through TUNEL and PCNA staining demonstrated the combination hydrogel not only significantly inhibited cell death but also significantly increased cell proliferation. The gene expression of inflammatory cytokines in rectal tissue, including IL-6 and IFN-γ was significantly decreased in the treatment group. The infiltration of immune cells including T cells (CD4) and macrophages (CD68), which are important components in the pathogenesis of radiation proctitis, as shown by immunohistochemistry of tissue samples, was significantly reduced in the treatment group compared to the control group. Conclusion These promising results suggest that the combination of curcumin and ginsenosides has therapeutic potential for the management of radiation proctitis and provide valuable insights into new therapeutic strategies in clinical applications.

More than one way to skin a dose volume: the impact of dose-surface map calculation approach on study reproducibility

Objective. Dose-surface maps (DSMs) provide spatial representations of the radiation dose to organ surfaces during radiotherapy and are a valuable tool for identifying dose deposition patterns that are predictive of radiation toxicities. Over the years, many different DSM calculation approaches have been introduced and used in dose-outcome studies. However, little consideration has been given to how these calculation approaches may be impacting the reproducibility of studies in the field. Therefore, we conducted an investigation to determine the level of equivalence of DSMs calculated with different approaches and their subsequent impact on study results. Approach. Rectum and bladder DSMs were calculated for 20 prostate radiotherapy patients using combinations of the most common slice orientation and spacing styles in the literature. Equivalence of differently calculated DSMs was evaluated using pixel-wise comparisons and DSM features (rectum only). Finally, mock cohort comparison studies were conducted with DSMs calculated using each approach to determine the level of dosimetric study reproducibility between calculation approaches. Main results. We found that rectum DSMs calculated using the planar and non-coplanar orientation styles were non-equivalent in the posterior rectal region and that equivalence of DSMs calculated with different slice spacing styles was conditional on the choice of inter-slice distance used. DSM features were highly sensitive to choice of slice orientation style and DSM sampling resolution. Finally, while general result trends were consistent between the comparison studies performed using different DSMs, statisitically significant subregions and features could vary greatly in position and magnitude. Significance. We have determined that DSMs calculated with different calculation approaches are frequently non-equivalent and can lead to differing conclusions between studies performed using the same dataset. We recommend that the DSM research community work to establish consensus calculation approaches to ensure reproducibility within the field.

Surgical Staplers in Laparoscopic Colectomy: A New Innovative Flexible Design Perspective

This article describes the development of a flexible surgical stapler mechanism, which serves as a fundamental tool for laparoscopic rectal cancer surgery, addressing the challenges posed by difficult types of accessibility using conventional instruments. The design of this mechanism involves the incorporation of a stacked tensegrity structure, in which a flexible beam serves as the central spine. To assess the stapler’s range of operation, an analysis of the workspace was conducted by examining collaborative Computed Tomography (CT) scan data obtained from different perspectives (Axial, Coronal, and Sagittal planes) at various intervals. By synthesizing kinematic equations, Hooke’s law was employed, taking into account rotational springs and bending moments. This allowed for precise control of the mechanism’s movements during surgical procedures in the rectal region. Additionally, the study examined the singularities and simulations of the tensegrity mechanism, considering the influential eyelet friction parameter. Notably, the research revealed that this friction parameter can alter the mechanism’s curvature, underscoring the importance of accurate analysis. To establish a correlation between the virtual and physical models, a preliminary design was presented, facilitating the identification of the friction parameter.

The Relationship Between the Resected Colon Length and the Number of Lymph Nodes in Colorectal Cancer: A Retrospective Cohort Study

Objective: The prognostic factors that are important for colorectal cancer are the pathological grade of the tumor and the existence of lymph node involvement. Currently, the curative treatment option is resection of the tumor with adequate length and margin along with complete dissection of lymph nodes draining the site of resection. Our study investigated into retrieving adequate lymph nodes for accurate staging as well as the relationship between lymph nodes and colon and rectum specimen length. Methods: This retrospective cross-sectional study examined the correlation between resected colon length and lymph node count in people with colorectal cancer diagnosed between January 2010 and June 2018. We defined a cutoff value for the segment length to be resected to allow adequate staging of the tumor. Furthermore, we examined the relationship between the resected segment lengths and survival. Results: Of the patients who were included in this study, 211 were men and 169 were women. The mean resected colon length was 26.47±17.09 cm and the mean dissected lymph node count was 29.05±20.84. There was a positive correlation between specimen length and total lymph node count as well as specimen length and the existence of reactive lymph nodes that were statistically significant (r=0.319, p=0.001; r=0.312, p=0.001, respectively). In our study, tumor localization was described in three regions: the right colon, left colon and rectum. The mean right colon region specimen length was 28.8±15.5 cm, while it was 22.0±11.0 cm for the left colon region, and 21.7±10.6 cm for the rectum region. The 5-year overall survival rate was 53.2%, whereas the 5-year disease-specific survival rate was 58.2%. Conclusion: The mean specimen length to achieve the cutoff value for adequate lymph node retrieval (least 12 lymph nodes) was 16 cm in our study (ROC curve, AUC=0.689±0.05, p=0.001). The resected colon length and the number of retrieved lymph nodes were positively correlated in our study. Based on this confirmation, a cutoff value of 16 cm was calculated to achieve an adequate segment length to be resected.

Excessive Glucose and Fructose Intake Aggravates the Pathogenesis of Rat Experimental Colitis

Ulcerative colitis (UC) is a relapsing and remitting disease that causes chronic inflammation and ulceration of colonic tissue, especially in the rectum region. Although sugars are rapidly digested and absorbed and can be efficiently utilized as energy in the body, they are also known to promote inflammation. Herein, we aimed to examine the effects of special diets containing excess glucose (Glu) or fructose (Fru) on the pathogenesis of dextran sulfate sodium (DSS)-induced UC in Wistar rats. The model rats (termed UC rats or UCR) were divided into three groups: DSS group, UCR fed a regular diet; DSS + Glu group, UCR fed a special diet mixed with glucose at 63% calories; DSS + Fru group, UCR fed a special diet mixed with fructose at 63% calories. The DSS + Glu and DSS + Fru groups exhibited a lower weight and colon length than the DSS group. The DSS + Fru group had a lower diet and DSS intake than the other two groups. The microscopic findings revealed that the DSS + Glu and DSS + Fru groups tended to have higher severity scores than the DSS group. The DSS + Fru group tended to have higher serum and colonic tissue concentrations of inflammatory cytokines than the DSS + Glu group. Collectively, these findings suggest that excessive glucose and fructose intake can aggravate intestinal inflammation.

Evaluation of Homocysteine, Trace Element, and Vitamin Levels in Male Individuals with Hemorrhoidal Disease

Objectives: Hemorrhoidal disease is a common and uncomfortable condition affecting people worldwide, primarily in the lower rectal region. This study explores the relationship between hemorrhoidal disease and the levels of homocysteine, folic acid, vitamin B12, zinc, and copper in men.&#x0D; Methods: A prospective study included 38 male patients with internal hemorrhoids (Group I) and 38 healthy male individuals (Group II). Venous blood samples were collected after a 12-hour fast and analyzed for homocysteine, folic acid, vitamin B12, zinc, and copper levels. Statistical analyses, including the Kolmogorov-Smirnov test, Mann-Whitney U or Two-Sample t-test, Receiver Operating Characteristic (ROC) analysis, and Multivariate Binary Logistic regression, were performed.&#x0D; Results: Group I and Group II had similar age and body mass index (BMI). Homocysteine and copper levels were significantly higher in Group I, while folic acid and vitamin B12 levels were significantly lower. High homocysteine levels (≥11.2 µmol/L) had a sensitivity of 92.11%, while low vitamin B12 (

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Automatic segmentation of rectal tumors from MRI using multiscale densely connected convolutional neural network based on attention mechanism

Rectal cancer is one of the most common malignancies in the gastrointestinal tract. Currently, magnetic resonance imaging has become a vital tool in diagnosing and treating patients with rectal cancer. Notably, early diagnosis of rectal cancer can help improve patient survival rate; however, the clinical expertize of physicians is a limiting factor. Therefore, we propose an attention-based multiscale densely connected convolutional neural network based on an attention mechanism to improve the accuracy of diagnosis by automatically segmenting rectal tumors from two-dimensional (2D) magnetic resonance images (MRI) using computer-aided diagnostic techniques. First, to address the inability of U-Net (a classical segmentation network for medical images) and extract rich semantic features and the inconsistent shape and size of tumors between different patients, we replace the conventional convolutional blocks in the U-Net network with multiscale densely connected convolutional blocks. Second, to make the network focus better on global contextual information, we add central blocks with atrous convolution in the final coding layer or the last coding layer. Finally, we add a hybrid attention mechanism to each decoder module to help the model focus on the features of the rectal tumor region. We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 572 patients. The sensitivity, specificity, Dice correlation coefficient, and Hausdorff distance of MRI rectal tumor segmentation were 85.47%, 86.35%, 94.71%, and 7.88 mm, respectively. The results showed that the proposed method outperforms conventional approaches. Moreover, the proposed method has better segmentation results in the rectal tumor segmentation task and can provide physicians with the second-most important clinical diagnostic opinion.

Colon-Adhering Delivery System with Inflammation Responsiveness for Localized Therapy of Experimental Colitis.

Ulcerative colitis (UC) is a chronic inflammation-related disease that severely affects the colon and rectum regions. A variety of therapy regimens are used for the treatment of UC. Clinically, therapeutic enema is the choice of therapy for UC patients. Irrespective of on-site administration, the major limitation of therapeutic enemas is the dispossession of the medicine followed by low drug availability for the therapeutic action. In our present work, we have developed an enzyme-responsive injectable hydrogel (ER-hydrogel) to overcome the limitations of therapeutic enema. The hydrogels possess two major advantages, which are being exploited for therapeutic drug delivery in UC: prolonged retention and enzyme responsiveness. The former is one of the prominent advantages of hydrogel compared to free drug enema and the latter controls the release of the drug or provides drug release on-demand. The ER-hydrogel was formulated by the heat-cool method and for therapeutic purposes, a corticosteroid drug, budesonide (Bud), was encapsulated into the ER-hydrogel and evaluated for its various physicochemical and therapeutic potentials in dextran sodium sulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirm the retention or mucoadhesive nature of the ER-hydrogel, and the upsurge in Bud release from the Bud-loaded ER-hydrogel upon the addition of esterase enzyme confirms the enzyme-mediated drug release from the ER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promising results in alleviating the disease activity index of UC, and restored the length of the colon, which is the main hallmark of UC. In terms of the health of the colon tissue, the Bud-loaded ER-hydrogel restored the colonic tissue damage, as seen in the H&E-stained, AB-NR-stained, and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogel also markedly subsided the IL-1β, TNF-α, MPO, and nitrite levels in serum and colon tissues. Thus, the fabricated Bud-loaded ER-hydrogel possesses appreciable translational potential due to its ability to significantly ameliorate inflammatory changes compared to naive or water-based therapeutic enema in acute experimental colitis in mice.

ID: 215134 Interpatient Variability in Neural Recruitment During Pudendal Nerve Stimulation - A Patient-Specific Computational Modeling Study

Pudendal nerve (PN) stimulation is an emerging neuromodulation technique for the treatment of refractory bladder dysfunction and pelvic pain, conditions affecting the quality-of-life and productivity of millions of individuals around the world. The PN is a mixed nerve originating from the S2-S4 sacral nerve roots and innervating the genital, perineal, and rectal regions. Although it has been studied extensively in preclinical settings, limited studies of PN stimulation have been performed in human subjects, and interpatient variability in outcomes are not well understood. Therefore, we created patient-specific computational models to study neural recruitment in human subjects undergoing PN stimulation as part of their clinical care.