Multi-Plant Assembly Planning Model in Collaborative Manufacturing and Commerce Systems

With emerging e-business models in a global supply chain, the components or parts of a product may be distributed and produced at various plants in a collaborative way for the purpose of expanding capacity and reducing costs. For an assembled product, the assembly operations for assembling the product may be performed at different assembly plants at various geographical locations. In the collaborative commerce environment, it is required to develop a multi-plant assembly planning model for orgaizing and distributing the assembly operations to the suitable plants for completing the final product. In this research, a multi-plant assembly planning model for generating and evaluating the multi-plant assembly sequences is presented. A graph-based model is developed to model and generate the assembly sequences. The feasible assembly sequences are analyzed and evaluated based on several cost objectives. The multi-plant assembly planning model is formulated with an aim of minimizing the total of assembly costs and multiplant costs. As a result, the optimized multi-plant assembly sequences can be obtained and each of the assembly operations is assigned to the suitable plant with a minimized cost. Example parts are tested and discussed

Using Botulinum Toxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome—Possible Pathomechanisms and Practical Issues

Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles in treating patients with IC/BPS. Although current guidelines consider BoNT-A injection to be a standard treatment, some practical issues remain debatable. Most clinical evidence of this treatment comes from retrospective uncontrolled studies, and only two randomized placebo-control studies with limited patient numbers have been published. Although 100 U BoNT-A is effective for most patients with IC/BPS, the potential efficacy of 200 U BoNT-A has not been evaluated. Both trigone and diffuse body BoNT-A injections are effective and safe for IC/BPS, although comparison studies are lacking. For IC/BPS patients with Hunner’s lesion, the efficacy of BoNT-A injection remains controversial. Most patients with IC/BPS experience symptomatic relapse at six to nine months after a BoNT-A injection, although repeated injections exhibit a persistent therapeutic effect in long-term follow-up. Further randomized placebo-controlled studies with a larger number of patients are needed to support BoNT-A as standard treatment for patients with IC/BPS

Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. Patients with Hunner’s lesion (HIC) and without Hunner’s lesion (NHIC) should be treated differently. Based on the histopathological findings, NHIC can be treated with intravesical instillation of urothelial protective agents, such as hyaluronic acid, to cover the urothelial defects. In non-responders, chronic inflammation and higher urothelial dysfunction can be treated with intravesical botulinum toxin A injection, platelet-rich plasma injection, or low-energy shock wave treatment to reduce inflammation, increase tissue regeneration, and improve the urothelial barrier. Patients with HIC should be treated with electrocauterization first; augmentation enterocystoplasty should only be used in end-stage HIC when the contracted bladder is refractory to other treatments. The antiviral agent, valacyclovir, can be used in patients with HIC, small bladder capacity, and high-grade glomerulations. In addition, behavioral modification is always recommended from the beginning of treatment. Treatment with cognitive behavioral therapy interventions in combination with bladder therapy can reduce anxiety and improve treatment outcomes. Herein, recent advances in the pathophysiology and novel treatments for IC/BPS are reviewed

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months’ duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment

Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention

Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market

Role of serum immunoglobulin E in patients with interstitial cystitis/bladder pain syndrome

Objective: The actual pathophysiology of interstitial cystitis (IC)/bladder pain syndrome (BPS) is still uncertain. Immune or hypersensitivity mechanisms may play an important role in the pathogenesis of IC/BPS. This study was designed to investigate and analyze serum immunoglobulin E (IgE) levels in patients with IC/BPS. Materials and methods: Patients with IC/BPS who were admitted for cystoscopic hydrodistention were enrolled in this study. Blood samples were obtained to investigate their serum IgE levels. A serum IgE level more than 200 IU/mL was considered abnormal. The patients' symptoms, visual analog scale (VAS) scores, O'Leary–Sant symptom (OSS) scores, cystometric bladder capacity (CBC), maximal bladder capacity (MBC), and grading of bladder glomerulation hemorrhage during cystoscopic hydrodistention were recorded. Serum IgE levels were also investigated in women with stress urinary incontinence, who served as the control group. Results: Two hundred patients with IC/BPS and 35 controls were investigated. In total, 22 IC/BPS patients (11%) had abnormal serum IgE levels. No abnormal serum IgE levels were detected in the controls. The mean serum IgE level in IC/BPS patients and controls were 102.37 IU/mL±250.68 IU/mL and 74.21 IU/mL±88.62 IU/mL, respectively (p = 0.204). The VAS, OSS, CBC, MBC, and grading of glomerulations were not significantly correlated with serum IgE levels (p = 0.317, 0.587, 0.774, 0.559, and 0.309, respectively). The serum IgE levels were slightly higher in men than in women, although the difference was not significant (152.98 IU/mL ± 201.73 IU/mL vs. 94.87 IU/mL±262.54 IU/mL, p = 0.183). Conclusion: In this study, 11% of patients with IC/BPS had IgE level more than 200 IU/mL, but the mean serum IgE level was not higher than the controls. Aggravating factors such as food or environmental substance should be carefully investigated in IC/BPS patients with elevated serum IgE levels

Botulinum Toxin A and Lower Urinary Tract Dysfunction: Pathophysiology and Mechanisms of Action

The use of onabotulinumtoxinA (BoNT-A) for the treatment of lower urinary tract diseases (LUTD) has increased markedly in recent years. The indications for BoNT-A treatment of LUTD now include neurogenic or idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome and voiding dysfunction. The mechanisms of BoNT-A action on LUTDs affect many different aspects. Traditionally, the effects of BoNT-A were believed to be attributable to inhibition of acetylcholine release from the presynaptic efferent nerves at the neuromuscular junctions in the detrusor or urethral sphincter. BoNT-A injection in the bladder also regulated sensory nerve function by blocking neurotransmitter release and reducing receptor expression in the urothelium. In addition, recent studies revealed an anti-inflammatory effect for BoNT-A. Substance P and nerve growth factor in the urine and bladder tissue decreased after BoNT-A injection. Mast cell activation in the bladder also decreased. BoNT-A-induced improvement of urothelium function plays an important mitigating role in bladder dysfunction. Vascular endothelial growth factor expression in urothelium decreased after BoNT-A injection, as did apoptosis. Studies also revealed increased apoptosis in the prostate after BoNT-A injection. Although BoNT-A injection has been widely used to treat different LUTDs refractory to conventional treatment, currently, onabotulinumtoxinA has been proven effective only on urinary incontinence due to IDO and NDO in several large-scale clinical trials. The effects of onabotulinumtoxinA on other LUTDs such as interstitial cystitis, benign prostatic hyperplasia, dysfunctional voiding or detrusor sphincter dyssynergia have not been well demonstrated