Fecobionics assessment of the effect of position on defecatory efficacy in normal subjects.

BACKGROUND: Defecation is a complex process and up to 25% of the population suffer from symptoms of defecatory dysfunction. For functional testing, diagnostics, and therapy of anorectal disorders, it is important to know the optimal defecation position. is The aim of this study was to evaluate defecation pressure patterns in side lying, seated and squatting defecation positions in normal subjects using a simulated stool device called Fecobionics. METHODS: The Fecobionics expulsion parameters were assessed in an interventional study design conducted from May 29 to December 9 2019. Subjects were invited to participate in the study through advertisement at The Chinese University of Hong Kong. The Fecobionics device consisted of a core containing pressure sensors at the front (caudal end) and rear (cranial end) and a polyester-urethane bag spanning most of the core length which also contained sensors. The Fecobionics bag was distended to 50 ml in the rectum of normal subjects (no present and past symptoms of defecatory disorders, no prior abdominal surgery, medication or chronic diseases). Studies were done in side lying (left lateral recumbent position), seated (hip flexed 90°) and squatting position (hip flexed 25°). Pressure endpoints including the rear-front pressure diagram and defecation indices were compared between positions. RESULTS: Twelve subjects (6 females/6 males, mean age 26.3 ± 2.6 [19.0-48.0] years) were included and underwent the planned procedures. The resting anal pressure for side lying and seated positions were 33.1 ± 4.1 cmH2O and 37.1 ± 4.0 cmH2O (p > 0.3). The anal squeeze pressure for side lying and seated positions were 98.4 ± 6.9 cmH2O and 142.3 ± 16.4 cmH2O (p < 0.05). The expulsion duration for the side lying, seated and squatting positions were 108.9 ± 8.3 s, 15.0 ± 2.1 s and 16.1 ± 2.9 s, respectively (p < 0.01 between lying and the two other positions). The maximum evacuation pressure for seated and squatting were 130.1 ± 12.4 cmH2O and 134.0 ± 11.1 cmH2O (p > 0.5). Rear-front pressure diagrams and distensibility indices demonstrated distinct differences in pressure patterns between the side lying position group and the other positions. CONCLUSIONS: The delay in expelling the Fecobionics device in the lying position was associated with dyssynergic pressure patterns on the device. Quantitative differences were not found between the seated and squatting position. Trial Registration http://www.clinicaltrials.gov Identifier: NCT03317938.

Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment for early stage CRC, adjuvant chemotherapy is usually given to reduce the risk of recurrence after colectomy. Overexpression of a multidrug resistance (MDR) transporter ABCG2 in vitro has been shown to cause resistance to 5-fluorouracil (5-FU) and irinotecan, components of the most commonly adopted regimens for treating CRC. Both anticancer drugs are known ABCG2 substrates. An effective way to predict drug response may provide guidance for better cancer treatment. We investigated the effect of ABCG2 dysregulation on cancer cell sensitivity to chemotherapy using pairs of snap-frozen paraffin-embedded archival blocks of human colorectal cancer tissues and their matched non-cancerous colon tissues from CRC patients. In CRC patients responding to chemotherapy, the tumors were found to have remarkable lower ABCG2 expression than the adjacent normal colon tissues. On the contrary, the tumors from patients not responding to 5-FU-based chemotherapy have higher ABCG2 level than the adjacent normal tissues. The high ABCG2 expression in the tumor is associated with the concomitant overexpression of the mRNA binding protein HuR but a low expression of miR-519c because miR-519c is known to target both ABCG2 and HuR. Further investigation in CRC cell lines revealed that the ABCG2 overexpression was caused by an interplay between miR-519c, HuR and the length of the 3' untranslated region (UTR) of ABCG2. These parameters may be further developed as useful biomarkers to predict patient response to adjuvant chemotherapy. Besides being predictive biomarkers, the microRNAs and mRNA binding protein identified may also be potential drug targets for modulating ABCG2 to combat resistance in CRC chemotherapy.

Electroacupuncture for ileus after laparoscopic colorectal surgery: a randomised sham-controlled study.

1. Electroacupuncture at acupoints of Zusanli, Sanyinjiao, Hegu, and Zhigou is more effective than no acupuncture and sham acupuncture in stimulating early return of bowel function and reducing analgesic requirement after laparoscopic colorectal surgery. 2. Electroacupuncture is more effective than no acupuncture in reducing the duration of hospital stay. 3. Receipt of electroacupuncture is an independent predictor of shorter duration of ileus and hospital stay after laparoscopic colorectal surgery.

New developments in defecatory studies based on biomechatronics.

Introduction: Defecation is a complex process that is difficult to study and analyze directly. In anorectal disease conditions, the defecation process may be disturbed, resulting in symptoms including fecal incontinence and constipation. Current state-of-the-art technology measures various aspects of anorectal function but detailed analysis is impossible because they are stand-alone tests rather than an integrated multi-dimensional test. Objectives: The need for physiologically-relevant and easy-to-use diagnostic tests for identifying underlying mechanisms is substantial. We aimed to advance the field with integrated technology for anorectal function assessment. Methods: We developed a simulated stool named Fecobionics that integrates several tests to assess defecation pressures, dimensions, shape, orientation and bending during evacuation. A novelty is that pressures are measured in axial direction, i.e. in the direction of the trajectory. Using this novel tool, we present new analytical methods to calculate physiologically relevant parameters during expulsion in normal human subjects. Results: Data are reported from 28 human subjects with progressively more advanced versions of Fecobionics. A new concept utilizes the rear-front pressure (preload-afterload) diagram for computation of novel defecation indices. Fecobionics obtained physiological data that cannot be obtained with current state-of-the-art technologies. Conclusion: Fecobionics measures well known parameters such as expulsion time and pressures as well as new metrics including defecation indices. The study suggests that Fecobionics is effective in evaluation of key defecatory parameters and well positioned as an integrated technology for assessment of anorectal function and dysfunction.

Computational Prediction and Experimental Realization of Earth-Abundant Transparent Conducting Oxide Ga-Doped ZnSb2O6.

Transparent conducting oxides have become ubiquitous in modern optoelectronics. However, the number of oxides that are transparent to visible light and have the metallic-like conductivity necessary for applications is limited to a handful of systems that have been known for the past 40 years. In this work, we use hybrid density functional theory and defect chemistry analysis to demonstrate that tri-rutile zinc antimonate, ZnSb2O6, is an ideal transparent conducting oxide and to identify gallium as the optimal dopant to yield high conductivity and transparency. To validate our computational predictions, we have synthesized both powder samples and single crystals of Ga-doped ZnSb2O6 which conclusively show behavior consistent with a degenerate transparent conducting oxide. This study demonstrates the possibility of a family of Sb(V)-containing oxides for transparent conducting oxide and power electronics applications.

Anion Distribution, Structural Distortion, and Symmetry-Driven Optical Band Gap Bowing in Mixed Halide Cs2SnX6 Vacancy Ordered Double Perovskites.

Mixed anion compounds in the Fm3̅m vacancy ordered perovskite structure were synthesized and characterized experimentally and computationally with a focus on compounds where A = Cs+. Pure anion Cs2SnX6 compounds were formed with X = Cl, Br, and I using a room temperature solution phase method. Mixed anion compounds were formed as solid solutions of Cs2SnCl6 and Cs2SnBr6 and a second series from Cs2SnBr6 and Cs2SnI6. Single phase structures formed across the entirety of both composition series with no evidence of long-range anion ordering observed by diffraction. A distortion of the cubic A2BX6 structure was identified in which the spacing of the BX6 octahedra changes to accommodate the A site cation without reduction of overall symmetry. Optical band gap values varied with anion composition between 4.89 eV in Cs2SnCl6 to 1.35 eV in Cs2SnI6 but proved highly nonlinear with changes in composition. In mixed halide compounds, it was found that lower energy optical transitions appeared that were not present in the pure halide compounds, and this was attributed to lowering of the local symmetry within the tin halide octahedra. The electronic structure was characterized by photoemission spectroscopy, and Raman spectroscopy revealed vibrational modes in the mixed halide compounds that could be assigned to particular mixed halide octahedra. This analysis was used to determine the distribution of octahedra types in mixed anion compounds, which was found to be consistent with a near-random distribution of halide anions throughout the structure, although some deviations from random halide distribution were noted in mixed iodide-bromide compounds, where the larger iodide anions preferentially adopted trans configurations.

Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia.

AIM: To compare the short term outcome of endoscopic submucosal dissection (ESD) with that of laparoscopic colorectal resection (LC) for the treatment of early colorectal epithelial neoplasms that are not amenable to conventional endoscopic removal. METHODS: This was a retrospective cohort study. The clinical data of all consecutive patients who underwent ESD for endoscopically assessed benign lesions that were larger than 2 cm in diameter from 2009 to 2013 were collected. These patients were compared with a cohort of controls who underwent LC from 2005 to 2013. Lesions that were proven to be malignant by initial endoscopic biopsies were excluded. Mid and lower rectal lesions were not included because total mesorectal excision, which bears a more complicated postoperative course, is not indicated for lesions without histological proof of malignancy. Both ESD and LC were performed by the same surgical unit with a standardized technique. The patients were managed according to a standard protocol, and they were closely monitored for complications after the procedures. All hospital records were reviewed, and the following data were compared between the ESD and LC groups: patient demographics, size and location of the lesions, procedure time, short-term clinical outcomes and pathology results. RESULTS: From 2005 to 2013, 65 patients who underwent ESD and 55 patients who underwent LC were included in this study. The two groups were similar in terms of sex (P = 0.41) and American Society of Anesthesiologist class (P = 0.58), although patients in the ESD group were slightly older (68.6 ± 9.4 vs 64.6 ± 9.9, P = 0.03). ESD could be accomplished with a shorter procedure time (113 ± 66 min vs 153 ± 43 min, P < 0.01) for lesions of comparable size (3.0 ± 1.2 cm vs 3.4 ± 1.4 cm, P = 0.22) and location (colon/rectum: 59/6 vs colon/rectum: 52/3, P = 0.43). ESD appeared to be associated with a lower short-term complication rate, but the difference did not reach statistical significance (10.8% vs 23.6%, P = 0.06). In the LC arm, a total of 22 complications occurred in 13 patients. A total of 7 complications occurred in the ESD arm, including 5 perforations and 2 episodes of bleeding. All perforations were observed during the procedure and were successfully managed by endoscopic clipping without emergency surgical intervention. Patients in the ESD arm had a faster recovery than patients in the LC arm, which included shorter time to resume normal diet (2 d vs 4 d, P = 0.01) and a shorter hospital stay (3 d vs 6 d, P < 0.01). CONCLUSION: ESD showed better short-term clinical outcomes in this study. Further prospective randomized studies will be required to evaluate the efficacy and superiority of colorectal ESD over LC.

The cytolytic effect of cobra cardiotoxin on Ehrlich ascites tumor cells and its inhibition by Ca2+.

In the presence of cobra cardiotoxin, cellular constituents from Ehrlich ascites tumor cells leak out into the medium. The leakage is detrimental to important cell functions. The rate of cardiotoxininduced cytolysis is dose-dependent and is not affected by cell concentration. Calcium ion inhibits the cytolysis reversibly; addition of calcium ion stops the cytolytic action whereas removal of calcium ion by EDTA abolishes the the inhibitory effect. Among the alkaline earth metals studied, Ca2+, Sr2+ and Ba2+ inhibit whereas Mg2+ potentiates the cytolysis. Progression of cytolysis requires a continuous presence of cardiotoxin; removal of cardiotoxin molecules by cardiotoxin antiserum completely abolishes the cytolytic activity. The ability of calcium ion to inhibit cardiotoxin-induced cytolysis is probably due to an interference of the binding of cardiotoxin molecules to the cell membrane.

Osteoclast inhibition by factors from cells associated with regenerative tissue.

Guided tissue regeneration (GTR) uses expanded polytetrafluoroethylene (ePTFE) membranes to favor the repopulation of the healing wound with cells with bone regenerative potential. As bone remodeling is a tightly coupled process, inhibition of osteoclast-mediated bone resorption may be critical to regeneration. Thus, this study was undertaken to determine whether cells associated with regenerative tissue can inhibit osteoclast differentiation and activity and to begin characterizing and identifying the factor(s) mediating the observed effects. Conditioned media were harvested from human periodontal cell lines established in culture: cells adherent to ePTFE membranes, recovered from patients after GTR; cells adherent to ePTFE augmentation membranes, recovered from edentulous ridge augmentation procedures; and periodontal ligament cells from periodontally healthy bicuspids. Conditioned medium from each of these regenerative cell lines reduced the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells formed from hemopoietic precursors in mouse bone marrow cultures. Also, both the total resorbed surface area and number of resorption pits formed by these cells on calcium phosphate ceramic films were reduced. The factor in the conditioned medium which inhibited osteoclast differentiation was soluble, heat labile, and resided in the lower molecular weight (< 30 kDa) fraction, the same fraction which would contain cytokines. Western blot analysis of the conditioned medium detected a band at the molecular weight of interferon gamma (IFN-gamma), using a polyclonal rabbit anti-human IFN-gamma. Thus, the factor in the conditioned medium with inhibitory activity may have identity with IFN-gamma or one of the other anti-inflammatory cytokines.

Role of whole-blood interferon-gamma release assay in the diagnosis of smear-negative tuberculosis.

SETTING: Hong Kong Chest Clinics. OBJECTIVES AND METHODS: To conduct a prospective study investigating the role of a whole-blood interferon-gamma release assay, QuantiFERON®-TB Gold In-Tube (QFT-GIT), in the diagnosis of smear-negative tuberculosis (TB). The QFT-GIT result was compared with the final confirmed diagnosis after 12 months. RESULTS: Of 262 smear-negative subjects, 188 had active TB, 167 (88.8%) of whom were QFT-GIT-positive; 74 had inactive/non-TB, 30 (40.5%) of whom were QFT-GIT-negative. The positive (PPV) and negative predictive values for active TB were respectively 79.1% and 58.8%. For this target group with high TB prevalence (71.8%), a positive test increased the chance of active disease by only 7.3%. Despite a positive likelihood ratio (LR) of 1.49, the negative LR was 0.28, making the diagnosis of active TB much less likely after a negative test. Although sensitivity and specificity showed no difference across different age groups, the PPV decreased (P < 0.001) with increasing age, likely reflecting the increased prevalence of competing diagnoses. CONCLUSION: In an area with a high prevalence of latent TB infection, a positive QFT-GIT test does not add much to confirm the diagnosis of smear-negative TB, while a negative test indicates a need for further investigation.

Quantitative evaluation of motor functional recovery process in chronic stroke patients during robot-assisted wrist training.

This study was to investigate the motor functional recovery process in chronic stroke during robot-assisted wrist training. Fifteen subjects with chronic upper extremity paresis after stroke attended a 20-session wrist tracking training using an interactive rehabilitation robot. Electromyographic (EMG) parameters, i.e., EMG activation levels of four muscles: biceps brachii (BIC), triceps brachii (TRI, lateral head), flexor carpiradialis (FCR), and extensor carpiradialis (ECR) and their co-contraction indexes (CI) were used to monitor the neuromuscular changes during the training course. The EMG activation levels of the FCR (11.1% of decrease from the initial), BIC (17.1% of decrease from the initial), and ECR (29.4% of decrease from the initial) muscles decreased significantly during the training (P<0.05). Such decrease was associated with decreased Modified Ashworth Scores for both the wrist and elbow joints (P<0.05). Significant decrease (P<0.05) was also found in CIs of muscle pairs, BIC&TRI (21% of decrease from the initial), FCR&BIC (11.3% of decrease from the initial), ECR&BIC (49.3% of decrease from the initial). The decreased CIs related to the BIC muscle were mainly caused by the reduction in the BIC EMG activation level, suggesting a better isolation of the wrist movements from the elbow motions. The decreased CI of ECR& FCR in the later training sessions (P<0.05) was due to the reduced co-contraction phase of the antagonist muscle pair in the tracking tasks. Significant improvements (P<0.05) were also found in motor outcomes related to the shoulder/elbow and wrist/hand scores assessed by the Fugl-Meyer assessment before and after the training. According to the evolution of the EMG parameters along the training course, further motor improvements could be obtained by providing more training sessions, since the decreases of the EMG parameters did not reach a steady state before the end of the training. The results in this study provided an objective and quantitative EMG measure to describe the motor recovery process during poststroke robot-assisted wrist for the further understanding on the neuromuscular mechanism associated with the recovery.

Transformation and allelic replacement in Francisella spp.

We describe methods for transposon mutagenesis and allelic replacement in the facultative intracellular pathogen Francisella. Recombinant clones were constructed by insertion of partially cut F. tularensis or F. novicida DNA into pUC19 and then mutagenized with a mini-Tn10-Km transposon. F. novicida could be transformed with these plasmids either by a chemical transformation method or by electroporation, whereas F. tularensis could be transformed only by electroporation. Transformation of F. tularensis by electroporation was enhanced in the absence of the capsule. Southern blot analysis showed that the KmR marker was rescued either by integration of the plasmid into the Francisella chromosome or by allelic replacement. Allelic replacement was found to be the mechanism underlying a site-specific mutation affecting FopA, an outer-membrane protein of Francisella. F. novicida could also be transformed with chromosomal DNA carrying the KmR marker and the transformation frequency obtained using chromosomal DNA was generally greater than that obtained using plasmid DNA. F. novicida was also transformed by an IncQ plasmid containing an F. novicida DNA insert, which replicated autonomously in this host.