Optimizing the utility of anorectal manometry for diagnosis and therapy: A roundtable review and recommendations

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders

Surgical Interventions and the Use of Device-Aided Therapy for the Treatment of Fecal Incontinence and Defecatory Disorders

The purpose of this clinical practice update expert review is to describe the key principles in the use of surgical interventions and device-aided therapy for managing fecal incontinence (FI) and defecatory disorders. The best practices outlined in this review are based on relevant publications, including systematic reviews and expert opinion (when applicable). Best Practice Advice 1: A stepwise approach should be followed for management of FI. Conservative therapies (diet, fluids, techniques to improve evacuation, a bowel training program, management of diarrhea and constipation with diet and medications if necessary) will benefit approximately 25% of patients and should be tried first. Best Practice Advice 2: Pelvic floor retraining with biofeedback therapy is recommended for patients with FI who do not respond to the conservative measures indicated above. Best Practice Advice 3: Perianal bulking agents such as intra-anal injection of dextranomer may be considered when conservative measures and biofeedback therapy fail. Best Practice Advice 4: Sacral nerve stimulation should be considered for patients with moderate or severe FI in whom symptoms have not responded after a 3-month or longer trial of conservative measures and biofeedback therapy and who do not have contraindications to these procedures. Best Practice Advice 5: Until further evidence is available, percutaneous tibial nerve stimulation should not be used for managing FI in clinical practice. Best Practice Advice 6: Barrier devices should be offered to patients who have failed conservative or surgical therapy, or in those who have failed conservative therapy who do not want or are not eligible for more invasive interventions. Best Practice Advice 7: Anal sphincter repair (sphincteroplasty) should be considered in postpartum women with FI and in patients with recent sphincter injuries. In patients who present later with symptoms of FI unresponsive to conservative and biofeedback therapy and evidence of sphincter damage, sphincteroplasty may be considered when perianal bulking injection and sacral nerve stimulation are not available or have proven unsuccessful. Best Practice Advice 8: The artificial anal sphincter, dynamic graciloplasty, may be considered for patients with medically refractory severe FI who have failed treatment or are not candidates for barrier devices, sacral nerve stimulation, perianal bulking injection, sphincteroplasty and a colostomy. Best Practice Advice 9: Major anatomic defects (eg, rectovaginal fistula, full-thickness rectal prolapse, fistula in ano, or cloaca-like deformity) should be rectified with surgery. Best Practice Advice 10: A colostomy should be considered in patients with severe FI who have failed conservative treatment and have failed or are not candidates for barrier devices, minimally invasive surgical interventions, and sphincteroplasty. Best Practice Advice 11: A magnetic anal sphincter device may be considered for patients with medically refractory severe FI who have failed or are not candidates for barrier devices, perianal bulking injection, sacral nerve stimulation, sphincteroplasty, or a colostomy. Data regarding efficacy are limited and 40% of patients had moderate or severe complications. Best Practice Advice 12: For defecatory disorders, biofeedback therapy is the treatment of choice. Best Practice Advice 13: Based on limited evidence, sacral nerve stimulation should not be used for managing defecatory disorders in clinical practice. Best Practice Advice 14: Anterograde colonic enemas are not effective in the long term for management of defecatory disorders. Best Practice Advice 15: The stapled transanal rectal resection and related procedures should not be routinely performed for correction of structural abnormalities in patients with defecatory disorders

The modulatory effect of septilin on cytotoxicity of cisplatin in a human breast adenocarcinoma cell line

435-441Cisplatin (Csp) is a recurrently used chemotherapeutic drug but its use is inadequate due to undesirable adverse effects. In search of alternative medicine more attention has been given to phytochemicals. Septilin (Spt), a polyherbal drug and its therapeutic potential is huge but there is a scarcity of studies on its cytotoxic potential on cancer cells. The current study was designed to examine the effects of Spt in combination with Csp on human breast adenocarcinoma (MCF-7) and normal human breast epithelial (MCF-10A) cell lines. Cell viability for Spt treated cells was studied using MTT assay. IC50 value of Csp on MCF-7 cells was found to be 10 µg/mL at 24 h. This dose was further used to study the combined effects of Csp with Spt on MCF-7 and MCF-10A cell lines. Maximum cytotoxicity of Spt on MCF-7 cells was observed at Spt 5 µg/mL. The mechanism of Spt induced cytotoxicity was studied using apoptosis assay. Spt did not show any cytotoxic effects on MCF-10 A normal human breast epithelial cells, indicating Spt has no effect on normal cells. Our findings suggest that Spt can be used in combination with an anticancer drug Csp to increase its efficacy and/or to minimize its side effects on normal cells

On the Importance of MC&A to Nuclear Security

Over the past fifty years, the threats posed by nuclear material and nuclear weapons have changed. These changes demand a new response. During the Cold War, the primary concern was that more States might establish programs to develop nuclear weapons. This is still a possibility, however, the concern of State proliferation of nuclear weapons has been joined by a new concern, namely the concern that a non-State actor might acquire a nuclear weapon or misuse nuclear or other radioactive material to create a disruptive nuclear security event. Because the threat has changed, international and national approaches to nuclear security need to change. Measures should be adopted world-wide that respond to the potential for a non-State actor to acquire and misuse nuclear material. (The primary subject of this paper is containing nuclear material threats. However, the same concepts that apply to nuclear material apply to other radioactive material, and from this point forward “nuclear material” could be interchanged with “nuclear and other radioactive material.”) The first step in preventing a non-State actor from acquiring nuclear material is for States to require nuclear facilities (i.e. organizations that possess nuclear material) to establish programs to maintain control over and account for the nuclear material that they possess. Most States already require a program of accounting for and control of nuclear material as part of their international nuclear safeguards programs. Enhancing existing nuclear material control and accounting (MC&A) programs could help to address the evolved threat to nuclear security, in addition to improving safeguards. This paper addresses the need to enhance existing MC&A programs to accommodate the needs of nuclear security. If you know what nuclear material you have, if you know where it is, and if you would recognize if it had gone missing, then you have taken the first step toward protecting people and the environment from misuse of it—one of the primary goals of nuclear security

The modulatory effect of septilin on cytotoxicity of cisplatin in a human breast adenocarcinoma cell line

Cisplatin (Csp) is a recurrently used chemotherapeutic drug but its use is inadequate due to undesirable adverse effects. In search of alternative medicine more attention has been given to phytochemicals. Septilin (Spt), a polyherbal drug and its therapeutic potential is huge but there is a scarcity of studies on its cytotoxic potential on cancer cells. The current study was designed to examine the effects of Spt in combination with Csp on human breast adenocarcinoma (MCF-7) and normal human breast epithelial (MCF-10A) cell lines. Cell viability for Spt treated cells was studied using MTT assay. IC50 value of Csp on MCF-7 cells was found to be 10 μg/mL at 24 h. This dose was further used to study the combined effects of Csp with Spt on MCF-7 and MCF-10A cell lines. Maximum cytotoxicity of Spt on MCF-7 cells was observed at Spt 5 μg/mL. The mechanism of Spt induced cytotoxicity was studied using apoptosis assay. Spt did not show any cytotoxic effects on MCF-10 A normal human breast epithelial cells, indicating Spt has no effect on normal cells. Our findings suggest that Spt can be used in combination with an anticancer drug Csp to increase its efficacy and/or to minimize its side effects on normal cells

Renormalization group study of the Kondo problem at a junction of several Luttinger wires

We study a system consisting of a junction of N quantum wires, where the junction is characterized by a scalar S-matrix, and an impurity spin is coupled to the electrons close to the junction. The wires are modeled as weakly interacting Tomonaga-Luttinger liquids. We derive the renormalization group equations for the Kondo couplings of the spin to the electronic modes on different wires, and analyze the renormalization group flows and fixed points for different values of the initial Kondo couplings and of the junction S-matrix (such as the decoupled S-matrix and the Griffiths S-matrix). We generally find that the Kondo couplings flow towards large and antiferromagnetic values in one of two possible ways. For the Griffiths S-matrix, we study one of the strong coupling flows by a perturbative expansion in the inverse of the Kondo coupling; we find that at large distances, the system approaches the ferromagnetic fixed point of the decoupled S-matrix. For the decoupled S-matrix with antiferromagnetic Kondo couplings and weak inter-electron interactions, the flows are to one of two strong coupling fixed points in which all the channels are strongly coupled to each other through the impurity spin. But strong inter-electron interactions, with K_\rho < N/(N+2), stabilize a multi-channel fixed point in which the coupling between different channels goes to zero. We have also studied the temperature dependence of the conductance at the decoupled and Griffiths S-matrices.Comment: Revtex4, 16 pages including 6 figure

Effects of the vibrating capsule on colonic circadian rhythm and bowel symptoms in chronic idiopathic constipation

BackgroundConstipated patients remain dissatisfied with current treatments suggesting a need for alternative therapies.AimEvaluate the mechanistic effects of oral vibrating capsule in chronic idiopathic constipation (CIC) by examining the temporal relationships between the onset of vibrations, complete spontaneous bowel movements (CSBM), and circadian rhythm.MethodsIn post hoc analyses of two double‐blind studies, CIC patients (Rome III) were randomized to receive 5 active or sham capsules/week for 8 weeks. The capsules were programmed for single vibration (study 1) or two vibration sessions with two modes, 8 hours apart (study 2). Daily electronic diaries assessed stool habit and percentage of CSBMs associated with vibrations. Responders were patients with ≥ 1 CSBM per week over baseline.Results250 patients were enrolled (active = 133, sham = 117). During and within 3 hours of vibration, there were significantly more % CSBMs in the active vs. sham group (50% vs. 42%; P = .0018). In study 2, there were two CSBM peaks associated with vibration sessions. Significantly more % CSBMs occurred in active mode 1 (21.5%) vs. sham (11.5%); (P = .0357). Responder rates did not differ in study 1 (active vs. sham: 26.9% vs. 35.9%, P = .19) or study 2 (mode 1 vs. sham: 50% vs. 31.8%, P = .24; mode 2 vs. sham: 38.1% vs. 31.8%, P = .75). Device was well‐tolerated barring mild vibration sensation.ConclusionsVibrating capsule may increase CSBMs possibly by enhancing the physiologic effects of waking and meals, and augmenting circadian rhythm, although responder rate was not different from sham. Two vibration sessions were associated with more CSBMs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163488/2/nmo13890.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163488/1/nmo13890_am.pd

Dirichlet Process Gaussian Mixture Models for Real-Time Monitoring and Their Application to Chemical Mechanical Planarization

The goal of this work is to use sensor data for online detection and identification of process anomalies (faults). In pursuit of this goal, we propose Dirichlet process Gaussian mixture (DPGM) models. The proposed DPGM models have two novel outcomes: 1) DP-based statistical process control (SPC) chart for anomaly detection and 2) unsupervised recurrent hierarchical DP clustering model for identification of specific process anomalies. The presented DPGM models are validated using numerical simulation studies as well as wireless vibration signals acquired from an experimental semiconductor chemical mechanical planarization (CMP) test bed. Through these numerically simulated and experimental sensor data, we test the hypotheses that DPGM models have significantly lower detection delays compared with SPC charts in terms of the average run length (ARL1) and higher defect identification accuracies (F-score) than popular clustering techniques, such as mean shift. For instance, the DP-based SPC chart detects pad wear anomaly in CMP within 50 ms, as opposed to over 140 ms with conventional control charts. Likewise, DPGM models are able to classify different anomalies in CMP

Quantification of Ultraprecision Surface Morphology using an Algebraic Graph Theoretic Approach

Assessment of progressive, nano-scale variation of surface morphology during ultraprecision manufacturing processes, such as fine-abrasive polishing of semiconductor wafers, is a challenging proposition owing to limitations with traditional surface quantifiers. We present an algebraic graph theoretic approach that uses graph topological invariants for quantification of ultraprecision surface morphology. The graph theoretic approach captures heterogeneous multi-scaled aspects of surface morphology from optical micrographs, and is therefore valuable for in situ real-time assessment of surface quality. Extensive experimental investigations with specular finished (Sa ~ 5 nm) blanket copper wafers from a chemical mechanical planarization (CMP) process suggest that the proposed method was able to quantify and track variations in surface morphology more effectively than statistical quantifiers reported in literature

Bacterial Endo-Symbiont Inhabiting Tridax procumbens L. and Their Antimicrobial Potential

Bacterial symbionts inhabiting Tridax procumbens L. were screened for antimicrobial potential with the aim to isolate potent bacteria bearing significant activity against test pathogens. The selected isolate was subjected to large scale fermentation to extract antimicrobial metabolite. The organic phase was reduced under vacuum pressure and crude ethyl acetate extract (10 mg/mL) was evaluated for antimicrobial activity against panel of test pathogens. The antibacterial activity was measured as a zone of inhibition and compared with standard antibiotics, gentamicin and tetracycline. Similarly, antifungal activity was compared with miconazole and bavistin. Significant activity was conferred against Shigella flexneri (MTCC 731) with 27±1.5 mm zone across the disc. Partially, purification of antimicrobial metabolite with TLC-bioautography and HPLC resulted in active fraction bearing activity at Rf 0.65 and eluting between 4 and 5 retention times. The obtained results are promising enough for future purification and characterization of antimicrobial metabolite. Thus, the study attributes to the growing knowledge on endophytes as one of the rich sources of antimicrobial potentials