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Bipolar membranes (BPMs) enable the operation of electrochemical reactors with electrode compartments in different chemical environments or pH. The transport properties at the microscopic scale are dictated by the composition and morphology of the interfacial junctions as well as the specific chemistry of the ion-exchange layers that support the current of protons and hydroxide ions. This work elucidates the relation between water-dissociation efficiency and the physicochemical properties of the individual ion-exchange membrane layers in the poly(styrene- b -poly(ethylene- ran -butylene)- b -polystyrene) (SEBS)-based BPM. The optimal water dissociation performance of three previously reported water-dissociation catalysts in the SEBS-based BPM was examined, with junction thickness of graphene oxide > TiO 2 > SnO 2 , resulting in disparate junction morphologies at the BPM's interface. A hybrid junction system, which included both the effective water dissociation catalyst SnO 2 and direct contacting of the ion-exchange membrane layer, exhibited high water dissociation efficiency. This was likely due to the immediate ion transport pathway provided by direct membrane contact around the catalyst, which also improved the interfacial adhesion. A higher ion exchange capacity (IEC) in BPMs substantially enhanced the water dissociation performance in BPMs without water-dissociation catalysts. However, the incorporation of the effective SnO 2 catalyst into the BPMs with a lower IEC significantly improved performance, an effect attributed to the hybrid junction system. Additionally, the increase in water uptake and ion conductivity of the cation exchange layer with higher IEC suggested that the cation exchange layer and its interface to the water-dissociation catalyst layer may play a key role in water dissociation. This study identifies the key parameters of individual BPM components and their interactions to water dissociation performance, offering new insights to guide in the construction of future BPMs optimized for enhanced water dissociation efficiency at high current densities.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is often resistant to therapy. An immune suppressive tumor microenvironment (TME) and oncogenic mutations in KRAS have both been implicated as drivers of resistance to therapy. Mitogen-activated protein kinase (MAPK) inhibition has not yet shown clinical efficacy, likely because of rapid acquisition of tumor-intrinsic resistance. However, the unique PDAC TME may also be a driver of resistance. We found that long-term focal adhesion kinase (FAK) inhibitor treatment led to hyperactivation of the RAS/MAPK pathway in PDAC cells in mouse models and tissues from patients with PDAC. Concomitant inhibition of both FAK (with VS-4718) and rapidly accelerated fibrosarcoma and MAPK kinase (RAF-MEK) (with avutometinib) induced tumor growth inhibition and increased survival across multiple PDAC mouse models. In the TME, cancer-associated fibroblasts (CAFs) impaired the down-regulation of MYC by RAF-MEK inhibition in PDAC cells, resulting in resistance. By contrast, FAK inhibition reprogramed CAFs to suppress the production of FGF1, which can drive resistance to RAF-MEK inhibition. The addition of chemotherapy to combined FAK and RAF-MEK inhibition led to tumor regression, a decrease in liver metastasis, and improved survival in KRAS-driven PDAC mouse models. Combination of FAK and RAF-MEK inhibition alone improved antitumor immunity and priming of T cell responses in response to chemotherapy. These findings provided the rationale for an ongoing clinical trial evaluating the efficacy of avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in patients with PDAC and may suggest further paths for combined stromal and tumor-targeting therapies.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Titanium and its alloys are extensively applied in artificial tooth roots because of their excellent corrosion resistance, high specific strength, and low elastic modulus. However, because of their biological inertness, their surface needs to be modified to improve the osteointegration of titanium implants. The preparation of biologically active calcium-phosphorus coatings on the surface of an implant is one effective method for enhancing the likelihood of bone integration. In this study, osteoinductive peptides were extracted from oyster shells by using acetic acid. Two peptide-containing hydroxyapatite (HA) composite coatings were then prepared: one coating was prepared by hydrothermally synthesizing an HA coating in the presence of peptides (HA/P/M), and the other coating was prepared by hydrothermally synthesizing HA and then immersing the hydrothermally synthesized HA in a peptide solution (HA/P/S). Characterization results indicated that the composite HA coatings containing oyster shell-based peptides were successfully prepared on the alkali-treated pure titanium surfaces. The HA/P/M and HA/P/S composite coatings were found to exhibit excellent hydrophilicity. Protein adsorption tests confirmed that the HA/P/M and HA/P/S coatings had an approximately 2.3 times higher concentration of adsorbed proteins than the pure HA coating.

Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes., Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery., Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor., Conclusion: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Purpose: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors., Materials and Methods: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore., Results: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively)., Conclusion: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes., (© 2024 Wiley Periodicals LLC.)

Ground glass hepatocytes (GGHs) have been associated with hepatocellular carcinoma (HCC) recurrence and poor prognosis. We previously demonstrated that pre-S expression in some GGHs is resistant to current hepatitis B virus (HBV) antiviral therapies. This study aimed to investigate whether integrated HBV DNA (iDNA) is the primary HBV DNA species responsible for sustained pre-S expression in GGH after effective antiviral therapy. We characterized 10 sets of micro-dissected, formalin-fixed-paraffin-embedded, and frozen GGH, HCC, and adjacent hepatitis B surface antigen-negative stained tissues for iDNA, pre-S deletions, and the quantity of covalently closed circular DNA. Eight patients had detectable pre-S deletions, and nine had detectable iDNA. Interestingly, eight patients had integrations within the TERT and CCNE1 genes, which are known recurrent integration sites associated with HCC. Furthermore, we observed a recurrent integration in the ABCC13 gene. Additionally, we identified variations in the type and quantity of pre-S deletions within individual sets of tissues by junction-specific PacBio long-read sequencing. The data from long-read sequencing indicate that some pre-S deletions were acquired following the integration events. Our findings demonstrate that iDNA exists in GGH and can be responsible for sustained pre-S expression in GGH after effective antiviral therapy., (© 2024 Wiley Periodicals LLC.)

The declining birth rate, population ageing and the outbound migration of young people in recent years have created obstacles for local companies in recruiting skilled personnel. Similar factors have also affected recruitment in the outlying island of Penghu, Taiwan. Multiple-attribute decision-making (MADM) techniques for evaluation model development were incorporated in the present research to investigate the key determinants of talent recruitment by the coffee house operators in the outlying island of Penghu. The decision-making trial and evaluation laboratory (DEMATEL) approach was first implemented to (i) examine the extent of mutual impact between evaluation predictors and (ii) develop an influential network relation map (NRM) for indicator and sub-indicator assessments. Subsequently, the DEMATEL-based analytic network process (DANP) technique was utilised to compute the weights of every indicator and sub-indicator. Additionally, the modified VlseKriterijumska Optimizcija I Kaompromisno Resenje or VIKOR (in Serbian) approach evaluated every indicator and sub-indicator performance gap for empirical data analysis with suggested conclusions and recommendations. The results showed that the first dimension that should be improved is past experience, followed by personality traits and professional competence, according to the causal diagram of the NRM. The weights acquired through the DANP indicated that professional competence was the most influential dimension, followed by personality traits, whereas past experience was the least influential. Past experience revealed that the highest gap value is the most important for development if coffee house operators want to attain the appropriate levels. Finally, the theoretical, managerial, and practical implications were discussed. Notably, the research outcomes could optimise talent recruitment, establish appropriate talent recruitment methods for coffee house operators, and enhance the human resource quality in the outlying island of Penghu., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Spinal cord injury (SCI) is a devastating condition that enormously affects an individual's health and quality of life. Neurogenic lower urinary tract dysfunction (NLUTD) is one of the most important sequelae induced by SCI, causing complications including urinary tract infection, renal function deterioration, urinary incontinence, and voiding dysfunction. Current therapeutic methods for SCI-induced NLUTD mainly target on the urinary bladder, but the outcomes are still far from satisfactory. Stem cell therapy has gained increasing attention for years for its ability to rescue the injured spinal cord directly. Stem cell differentiation and their paracrine effects, including exosomes, are the proposed mechanisms to enhance the recovery from SCI. Several animal studies have demonstrated improvement in bladder function using mesenchymal stem cells (MSCs) and neural stem cells (NSCs). Human clinical trials also provide promising results in urodynamic parameters after MSC therapy. However, there is still uncertainty about the ideal treatment window and application protocol for stem cell therapy. Besides, data on the therapeutic effects regarding NSCs and stem cell-derived exosomes in SCI-related NLUTD are scarce. Therefore, there is a pressing need for further well-designed human clinical trials to translate the stem cell therapy into a formal therapeutic option for SCI-induced NLUTD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During the SARS-CoV-2 pandemic, the use of in-laboratory positive airway pressure (PAP) titration studies was not routinely suggested. PAP pressure prediction calculations are emerging as alternative methods for the treatment of these patients. The underestimation of PAP titration pressure usually leads to unsatisfactory results for PAP therapy. This study aimed to evaluate the factors associated with the underestimation of PAP titration pressure when using PAP pressure prediction equations. Estimated PAP pressure formulas based on body mass index (BMI) and apnea-hypopnea index (AHI) were chosen to validate the accuracy of equations in the successful prediction of titration pressure. Among 341 adult patients diagnosed with obstructive sleep apnea (OSA) by overnight polysomnography (PSG) and who received overnight PAP titration in order to select a successful pressure, the mean age of the total subjects was 55.4 years old and 78.9% of patients were male. The average BMI and AHI scores were 27.1 ± 4.8 and 37 ± 21.7, respectively. After multivariate stepwise regression analysis, the odds ratio of participants with a pretitration AHI was 1.017 (95% CI: 1.005-1.030). Only the severity of OSA was significantly different between the underestimated group and the adequately assessed group. In conclusion, a high AHI, but not BMI, is associated with an underestimated CPAP titration pressure in adult patients with OSA.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

Background and Objective: The aim of this study was to investigate the factors affecting extrusion time in both children and adults with ventilation tube (VT) insertion, providing useful information for clinicians for better decision-making, follow strategy, and potentially improve clinical outcomes for these patients., Methods: Data from patients receiving myringotomy with VT insertion from January 1, 2007, to June 30, 2012, were retrospectively collected and analyzed by the end of 2018. Various factors, including age, gender, history of VT insertion, tympanogram, size of VT used, local finding of tympanic membrane, hypertension, diabetes mellitus, hyperlipidemia, and postoperative ear infection, were included and analyzed to examine the effects of these factors on extrusion time., Results: A total of 447 patients were included in this study (Child group-Adult group = 237:210). The overall average extrusion time was 225.85 days. In the subgroup analysis, the average time was 221.3 days and 231.0 days for children and adults, respectively. The results showed that the VT extrusion time was significantly longer in participants without a history of VT insertion and in those where larger sized VTs were inserted in both age-groups. Male gender had an influence on extrusion time in children. In addition, a history of VT insertion and VT size were determined to be factors related to extrusion before 12 months in children., Conclusion: History of VT insertion and VT size were significantly related to VT extrusion time in both children and adults and defined as factors associated with extrusion before 12 months in children. The findings suggest avoiding VT with a diameter < 1 mm and considering an appropriately larger size in patients with a history of VT insertion to optimize VT retention.

Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged ≥75 years, and to identify factors associated with unfavorable outcomes. Patients receiving intradetrusor injections of 100 U onabotulinumtoxinA for refractory OAB between 2011 and 2021 were retrospectively reviewed. Urodynamic parameters, underlying comorbidities, subjective success, and unfavorable outcomes were assessed. A total of 192 patients were included, and 65 of them were classified into the elderly group. For the elderly group, 60.0% experienced subjective dryness, and 84.6% remained subjective success at 6 months after the injections. The prevalence rates of common unfavorable outcomes, including urinary tract infections, large post-void residual urine volume, and urinary retention, were 9.2%, 27.7%, and 12.3%, respectively. Multivariate analysis revealed that female, baseline urodynamic parameters, and diabetes mellitus were associated with unfavorable outcomes in the elderly group. Intravesical BoNT-A injections provide comparable therapeutic efficacy and safety concerns in elderly patients with refractory OAB. A thorough consultation for treatment benefits and possible adverse events is mandatory before the procedure.

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that it may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we find that centrosomes are highly accessible to soluble molecules with a Stokes radius of less than 5.8 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of this barrier is tightly regulated by branched actin filaments outside of centrosomes and it decreases during anaphase when branched actin temporally increases. The actin-based diffusion barrier gates microtubule nucleation by interfering with γ-tubulin ring complex recruitment. We propose that actin filaments spatiotemporally constrain protein complexes at centrosomes in a size-dependent manner., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Objectives: The aim was to investigate the feasibility and effects of an eight-week multimodal exercise program in sedentary postmenopausal women with urinary incontinence (UI) compared with pelvic floor muscle training (PFMT) only., Study Design: This was a pilot randomized controlled trial. The participants were randomly allocated to either the intervention group (IG), who received a multimodal exercise program that incorporated aerobic exercise, resistance exercise, and PFMT, or the control group (CG), who received PFMT only. The intervention was provided twice weekly for eight weeks., Main Outcome Measures: The primary outcome was feasibility in relation to consent rate, attendance, withdrawal rate, satisfaction with program, and adverse events. The secondary outcomes included pelvic floor muscle function (assessed using digital palpation and manometry), UI-specific quality of life (QoL) (rated on the International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]), symptom severity (assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form [ICIQ-UI SF] and a bladder diary), and physical activity levels (rated on the International Physical Activity Questionnaire- short form [IPAQ])., Results: Thirty-three of 63 eligible participants (52.4 %) consented to participate in the study and 26 completed it (IG n = 13, CG n = 13); the withdrawal rate was lower in the IG than in the CG (13.3 % vs 27.8 %). In both groups the attendance rate was 100 % and the satisfaction rate was 84.6 %. No adverse events were reported. The intention-to-treat analysis showed that UI-specific QoL (p = 0.011, mean difference: -5.62, 95 % CI: -9.67 to -1.57) and symptom severity measured using the ICIQ-UI SF (p = 0.001, mean difference: -3.23, 95 % CI: -4.93 to -1.54) were significantly improved in the IG after intervention, while no significant changes were found in the CG after intervention. The daytime frequency (p = 0.001) and number of leakages (p = 0.045) recorded in the bladder diary were significantly reduced in the CG after intervention. No significant differences between groups were found on any of the outcome measurements after intervention, except the daytime frequency from the bladder diary, which was significantly more reduced in the CG than in the IG (p = 0.003, mean difference: -0.28, 95 % CI: -2.25 to 1.67)., Conclusion: An eight-week multimodal exercise program is feasible for sedentary postmenopausal women with UI, and the multimodal exercise program demonstrated potential benefits for improving UI-specific QoL and symptom severity in this population. The trial was registered at ClinicalTrials.gov (NCT04351750)., Competing Interests: The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, non-neurogenic voiding dysfunction. Patients who received urethral sphincter BoNT-A injection for refractory voiding dysfunction due to detrusor underactivity (DU) or urethral sphincter dysfunction were retrospectively reviewed. A successful outcome was defined as a marked improvement as reported in the global response assessment. The study evaluated the therapeutic efficacy of urethral sphincter BoNT-A injections and measured the changes in urodynamic parameters after the procedure in the patients. A total of 181 patients including 138 women and 43 men were included. The overall success rate was 64%. A lower success rate was noted in patients with DU compared to those with urethral sphincter dysfunction in both genders. In the multivariable analysis, recurrent urinary tract infection (UTI) and bladder voiding efficiency (BVE) were positive predictors for a successful outcome, while DU was a negative predictor. Urethral sphincter BoNT-A injection is an effective treatment for refractory non-neurogenic voiding dysfunction. Baseline BVE and history of recurrent UTI positively predict a successful outcome. DU is a negative outcome predictor.

Purpose: To describe the investigation and intervention of a cluster of Legionnaires' disease detected during the outbreak of coronavirus disease 2019 (COVID-19) pandemic., Methods: From June 7 to 22, 2021, 15 cases in the neighborhood near our hospital were detected. Information about residence, workplace, hospital visit, and potential exposures was collected. Sampling and decontamination were performed for potential sources., Results: All 15 patients had pneumonia when visiting the emergency room with negative COVID-19 test results. Most patients were male (73.3%) with the mean age of 65.7 years. The most common comorbidities were diabetes mellitus (40.0%) and hypertension (40%). The most common symptom was fever (93.3%). Two (13.3%) patients needed mechanical ventilators. Fever subsided within 2 days of treatment for most cases (85.7%). Five cases had exposure history at our hospital, and the other 10 lived or worked in the area within 2 km of our hospital, mostly in buildings A and B. Water sampling was carried out for our hospital, buildings A and B; one water sample from a cooling tower in our hospital cultured positive for Legionella bacteria. Early testing and treatment for suspected cases were carried out for the outbreak, and all cases were discharged with pneumonia resolution., Conclusion: This was a community outbreak of Legionnaires' disease near our hospital. COVID-19 tests were repeated frequently before testing for Legionnaires' disease during the COVID-19 pandemic. Early recognition of Legionnaires' disease and timely treatment improved outcome., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. No funding sources had any role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript., (Copyright © 2022. Published by Elsevier B.V.)

A bimetallic Fe/Al disinfection system was developed to examine the feasibility of inactivation of water borne microorganisms. In this study, the effectiveness and mechanisms of the bimetallic Fe/Al system on the inactivation of model bacteria, Escherichia coli (E. coli), were investigated. Results revealed that the Fe/Al system effectively inactivated E. coli to reach nearly 2 logs (99%) removal within 20 min and 4 logs (99.99%) at 24 h, indicating that the Fe/Al composite was able to sustain a long-term disinfection capacity. The inactivation ability resulted from hydroxyl radicals produced by a Fenton reaction through in-situ self-generated Fe 2+ and H 2 O 2 species in the Fe/Al system. In addition to the attack by the radicals, some of E. coli were adsorbed onto the Fe/Al composite (zeta potential of 30-50 mV) as a result of Coulomb interaction. Scanning electron microscope (SEM) images showed that the adsorbed bacteria had damaged pores at the two ends of their rod-like cells. This phenomenon suggested that a micro-electric field between the Fe/Al galvanic couple induced electroporation of the adsorbed E. coli and thus further advanced additional inactivation ability for the bacteria disinfection., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bladder dysfunction, which involves inadequacies of urine storage or emptying, increases with age. Conventional medications may have insufficient efficacy for patients with refractory lower urinary tract symptoms, and their concomitant adverse events (AEs) may be intolerable for the older adult population. For decades, the botulinum toxin type A (BoNT-A) injection has been an option for managing urine frequency, urge incontinence, and voiding dysfunction in the general population refractory to conventional management. This review focuses on studies of BoNT-A application in the management of bladder dysfunction in older adult patients aged ≥ 65 years. In this target population, intravesical BoNT-A injections provide similar efficacy in idiopathic overactive bladder to that in younger adults. Good clinical response has also been demonstrated in older adult patients presenting with storage dysfunction and with various concomitant underlying neurological diseases. However, caution must be taken for the AEs that occur after intravesical BoNT-A injection, including increased post-void residual urine, acute urine retention, and urinary tract infection. Most evidence shows that age is not a major determinant of AEs after adjusting for other factors. In contrast to its application in storage dysfunction, evidence for voiding dysfunction in older adults is scarce. In general, BoNT-A may be a reasonable option for older adult patients with refractory storage dysfunction because of its promising clinical response without significant systemic AEs. Overall, clinicians should be aware of the balance between the therapeutic efficacy of BoNT-A and local AEs in vulnerable members of this population., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The prognosis of patients undergoing 2-sided radical nephroureterectomies (RNUs) with a residual bladder due to bilateral upper tract urothelial carcinoma (UTUC) is poorly understood. This study was aimed toward surveying the oncology outcomes and prognostic factors that may help in shared decision-making related to bladder preservation in patients preparing to receive 2-sided RNUs., Methods: Patients with synchronous or metachronous bilateral UTUC who received bilateral RNUs with a residual bladder in our hospital were retrospectively reviewed. Clinical and pathological data were analyzed for potential variables affecting the oncology outcomes., Results: A total of 50 patients were included. The average age at completion of the 2-sided RNU was 62.7 ± 12.4 years, with a mean follow-up of 88.4 ± 59.3 months after the 2-sided RNUs. The medium overall survival was 13.4 ± 1.8 years. Twenty-six patients (52%) had cancer recurrence in the residual bladder, but only 2 (8%) of the recurrences were muscle invasive. The highest UTUC stage was the only predictive factor for cancer-specific survival (CSS) rather than intravesical recurrence. The 5 year CSS rates in patients with the highest UTUC stage ≦ pT2 and ≧ pT3 were 90% and 51%, respectively (p = 0.007)., Conclusions: Risk of cancer recurrence in the residual bladder is high, but does not affect survival outcomes. The highest UTUC stage plays a significant role in cancer-specific survival. With a careful patient surveillance, bladder preservation may be reasonable in patients with bilateral UTUC preparing for 2-sided RNUs., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Chronic rhinosinusitis affects approximately 5%-2% of the general population worldwide. Steroid implants after endoscopic sinus surgery (ESS) have drawn considerable interest for their cost savings, but relevant guidelines indicate that evidence on this topic is of low quality with high heterogeneity. The purpose of this study was to examine the efficacy of steroid implants after ESS by synthesizing relevant randomized controlled trials (RCTs)., Methods: Two authors independently assessed the eligibility of potential references from five biomedical databases. They further extracted relevant data from the included studies, including (a) mean, standard deviation, or standard error for Lund-Kennedy endoscopic (LKE) score and Perioperative Sinus Endoscopy (POSE) score and (b) events and sample sizes of each group for further intervention. Data were pooled in a random-effects model, and results were presented as the weighted mean difference (WMD) or risk ratio (RR) with 95% confidence interval (CI) and I 2 ., Results: Eleven RCTs (n = 853) were included and showed that the steroid implant group had lower LKE scores (WMD, -1.19; 95% CI, -1.75 to -0.62; I 2  = 0%) and POSE scores (WMD, -1.62; 95% CI, -2.47 to -0.76; I 2  = 48%) than the placebo implant group at postoperative week 2. Moreover, the reoperation rate in the steroid implant group was also lower than in the placebo implant group (RR, 0.49; 95% CI, 0.30 to 0.80; I 2  = 0%). However, no significant difference was observed in the postoperative oral steroid requirement between both groups., Conclusions: Collectively, steroid implant decreases LKE and POSE among patients receiving ESS in the short term, but long-term effects remain unclear. Patient-based outcomes are worth further discussion in the future., (© 2021 ARS-AAOA, LLC.)

Integrated hepatitis B virus (HBV) DNA, found in more than 85% of HBV-associated hepatocellular carcinomas (HBV-HCCs), can play a significant role in HBV-related liver disease progression. HBV-host junction sequences (HBV-JSs), created through integration events, have been used to determine HBV-HCC clonality. Here, we investigate the feasibility of analyzing HBV integration in a noninvasive urine liquid biopsy. Using an HBV-targeted next-generation sequencing (NGS) assay, we first identified HBV-JSs in eight HBV-HCC tissues and designed short-amplicon junction-specific polymerase chain reaction assays to detect HBV-JSs in matched urine. We detected and validated tissue-derived junctions in five of eight matched urine samples. Next, we screened 32 urine samples collected from 25 patients infected with HBV (5 with hepatitis, 10 with cirrhosis, 4 with HCC, and 6 post-HCC). Encouragingly, all 32 urine samples contained HBV-JSs detectable by HBV-targeted NGS. Of the 712 total HBV-JSs detected in urine, 351 were in gene-coding regions, 11 of which, including TERT (telomerase reverse transcriptase), had previously been reported as recurrent integration sites in HCC tissue and were found only in the urine patients with cirrhosis or HCC. The integration breakpoints of HBV DNA detected in urine were found predominantly (~70%) at a previously identified integration hotspot, HBV DR1-2 (down-regulator of transcription 1-2). Conclusion: HBV viral-host junction DNA can be detected in urine of patients infected with HBV. This study demonstrates the potential for a noninvasive urine liquid biopsy of integrated HBV DNA to monitor patients infected with HBV for HBV-associated liver diseases and the efficacy of antiviral therapy., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Objectives: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes., Results: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001)., Conclusions: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.

Whole-cell biosensors are useful for monitoring heavy metal toxicity in public health and ecosystems, but their development has been hindered by intrinsic trade-offs between sensitivity and specificity. Here, we demonstrated an effective engineering solution by building a sensitive, specific, and high-response biosensor for carcinogenic cadmium ions. We genetically programmed the metal transport system of Escherichia coli to enrich intracellular cadmium ions and deprive interfering metal species. We then selected 16 cadmium-sensing transcription factors from the GenBank database and tested their reactivity to 14 metal ions in the engineered E. coli using the expression of the green fluorescent protein as the readout. The resulting cadmium biosensor was highly specific and showed a detection limit of 3 nM, a linear increase in fluorescent intensities from 0 to 200 nM, and a maximal 777-fold signal change. Using this whole-cell biosensor, a smartphone, and low-tech equipment, we developed a simple assay capable of measuring cadmium ions at the same concentration range in irrigation water and human urine. This method is user-friendly and cost-effective, making it affordable to screen large amounts of samples for cadmium toxicity in agriculture and medicine. Moreover, our work highlights natural gene repositories as a treasure chest for bioengineering.

GNRA tetraloop-binding receptor interactions are key components in the macromolecular assembly of a variety of functional RNAs. In nature, there is an apparent bias for GAAA/11nt receptor and GYRA/helix interactions, with the former interaction being thermodynamically more stable than the latter. While past in vitro selections allowed isolation of novel GGAA and GUGA receptors, we report herein an in vitro selection that revealed several novel classes of specific GUAA receptors with binding affinities comparable to those from natural GAAA/11nt interactions. These GUAA receptors have structural homology with double-locked bulge RNA modules naturally occurring in ribosomal RNAs. They display mutational robustness that enables exploration of the sequence/phenotypic space associated to GNRA/receptor interactions through epistasis. Their thermodynamic self-assembly fitness landscape is characterized by a rugged neutral network with possible evolutionary trajectories toward natural GNRA/receptor interactions. High throughput sequencing analysis revealed synergetic mutations located away from the tertiary interactions that positively contribute to assembly fitness. Our study suggests that the repertoire of GNRA/receptor interactions is much larger than initially thought from the analysis of natural stable RNA molecules and also provides clues for their evolution towards natural GNRA/receptors., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Generic quality of life (QoL) is an important issue in decision making related to the primary treatment of localized prostate cancer (PC). This study assessed the dynamic changes of QoL in patients with localized PC under different treatment modalities. From 2013 to 2018, we prospectively assessed QoL scores in patients with localized PC under unitary treatment using the World Health Organization Quality of Life (WHOQOL) BREF version. The trajectories of the QoL scores after different treatments were estimated using a kernel-smoothing method. Dynamic changes in the major determinants were analyzed using a mixed effects model. The clinical features of the participants in our institute were compared with PC patients in Taiwan's cancer registry. A total of 196 patients were enrolled with 491 repeated assessments. The participants shared similar clinical characteristics with the PC patients in Taiwan as a whole. Patients with lower household incomes showed statistically significant lower scores on all four domains and related facets, while PC survivors with comorbidities of anxiety and/or diabetes appeared to be affected on the physical domain and related facets. After controlling for these determinants, patients under active surveillance or observation demonstrated significantly higher QoL scores in the physical and social domains, as well as several facets belonging to these domains, in mixed models compared with patients undergoing radical prostatectomy or radiotherapy within the first year. The generic QoL scores were higher within the first year in patients receiving active surveillance or observation after controlling other significant factors. The difference diminished after one year of post management. More studies are needed to corroborate our findings.

Introduction: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries., Objective: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries MATERIALS AND METHODS: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction., Results: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction., Conclusions: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler's syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed.

Background: The advancements in cancer therapy have improved the clinical outcomes of cancer patients in recent decades. However, advanced cancer therapy is expensive and requires good health care systems. For kidney cancer, no studies have yet established an association between clinical outcome and health care disparities., Methods: We used the mortality-to-incidence ratio (MIR) for kidney cancer as a marker of clinical outcome to compare World Health Organization (WHO) country rankings and total expenditures on health/gross domestic product (e/GDP) using linear regression analyses., Results: We included 57 countries based on data from the GLOBOCAN 2012 database. We found that more highly developed regions have higher crude and age-standardized rates of kidney cancer incidence and mortality, but a lower MIR, when compared to less developed regions. North America has the highest crude rates of incidence, but the lowest MIRs, whereas Africa has the highest MIRs. Furthermore, favorable MIRs are correlated with countries with good WHO rankings and high e/GDP expenditures (p < 0.001 and p = 0.013, respectively)., Conclusions: Kidney cancer MIRs are positively associated with the ranking of health care systems and health care expenditures.

We developed an ultrasound-chemical hybrid tool to precisely manipulate cellular activities. A focused ultrasound coupled with gas-filled microbubbles was used to rapidly trigger the influx of membrane-impermeable chemical dimerizers into living cells to regulate protein dimerization and location without inducing noticeable toxicity. With this system, we demonstrated the successful modulation of phospholipid metabolism triggered by a short pulse of ultrasound exposure. Our technique offers a powerful and versatile tool for using ultrasound to spatiotemporally manipulate the cellular physiology in living cells.

The variation in the mortality-to-incidence ratio (MIR) between countries and genders reflects the complex etiology and intervention of bladder cancer. In this study, we investigated the MIR variation between genders and health care disparities among countries. Cancer incidence and mortality were obtained from the GLOBOCAN 2012 database. The ranking and the total expenditure on health of countries were obtained from the World Health Organization. Linear regression was used to estimate the significance between variables. We estimated the role of MIRs from 33 countries. Bladder cancer incidence and mortality rates were higher in more developed regions, Europe, and the Americas. The MIRs were higher in less developed regions. Analysis according to country revealed Germany to have the lowest MIR. High relative MIRs (female MIR/male MIR) for bladder cancer were noted in many developed countries. A correlation between MIR and health care disparities among countries was indicated by a significant association between the World Health Organization ranking and total expenditure on health/GDP with the MIR and relative MIR. Low bladder cancer MIR is prone to be more prevalent in countries with good health care system.

The variation in mortality-to-incidence ratios (MIRs) among countries reflects the clinical outcomes and the available interventions for colorectal cancer treatments. The association between MIR of prostate cancer and cancer care disparities among countries is an interesting issue that is rarely investigated. For the present study, cancer incidence and mortality rates were obtained from the GLOBOCAN 2012 database. The rankings and total expenditures on health of various countries were obtained from the World Health Organization (WHO). The association between variables was analyzed by linear regression analyses. In this study, we estimated the role of MIRs from 35 countries that had a prostate cancer incidence greater than 5,000 cases per year. As expected, high prostate cancer incidence and mortality rates were observed in more developed regions, such as Europe and the Americas. However, the MIRs were 2.5 times higher in the less developed regions. Regarding the association between MIR and cancer care disparities, countries with good WHO ranking and high total expenditures on health/gross domestic product (GDP) were significant correlated with low MIR. The MIR variation for prostate cancer correlates with cancer care disparities among countries further support the role of cancer care disparities in clinical outcome.

A 67-year-old man with a biopsy proving prostate diffuse large B-cell lymphoma was referred for an F-FDG PET/CT scan for postchemotherapy treatment monitoring. The FDG PET/CT scan revealed a significant reduction of prostate lymphoma and a prostatorectal fistula formation. The patient developed Klebsiella pneumoniae sepsis, and a follow-up FDG PET/CT 3 months later revealed multifocal lung, bone, and muscle infection. The FDG PET/CT scans of this patient not only demonstrated the effectiveness of chemotherapy for prostate lymphoma but also the complications of a prostatorectal fistula and multiple infectious foci.

This work demonstrates the efficiency and directionality of a method of extracting light from thin-film emissive devices by near-field evanescent waves in plasmonic emitters used in metal composite grating structures. A near-field evanescent wave can induce a surface plasmon wave on the surface of a metal under resonant conditions. Enhancing the near-field evanescent wave generates strong far-field nonlinear optical effects. This effect is highly efficient in some plasmonic emitter structures. Theoretical and experimental results demonstrate that such a metal composite grating structure exhibits good performance, a high coupling ratio, a small coupling angle, enhanced light extraction and a small FWHM. It also improves luminous efficiency, emitter angle, and directivity.

A 43-year-old male patient with follicular B-cell lymphoma was referred for a FDG PET/CT scan due to severe left lower abdominal pain to rule out recurrent cancer. These FDG PET/CT images and previous FDG PET/CT images 5 months ago both revealed an air bubble in the urinary bladder on the CT images. He had a recurrent urinary tract infection history for 6 months. A list-mode dynamic data acquisition with diuresis intravenous injection revealed linear FDG activity extending from the upper-left portion of the bladder to a soft tissue mass in the lower-left pelvic region. An enterovesical fistula was confirmed by surgery.

Driving a bus is a stressful job, and may result in aberrant behaviors or health problems. The purpose of this study is to investigate the effects of bus driver burnout on aberrant behaviors and health problems, as well as the role of self-criticism and confrontive and reappraisal coping as moderator variables in the hassle-burnout relationship. A self-administered questionnaire was designed to collect empirical data from bus drivers working at a Taiwanese motor transport company. The results confirm that burnout has a significantly positive relationship with both health problems and aberrant driving behaviors. In addition, although self-criticism positively moderates the relationship between job hassles and burnout, confrontive and reappraisal coping negatively moderate it., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Reports on foreign bodies within the ureter are extremely rare in the literature. Herein, we present a case of a foreign body in a ureter, specifically a particle of glue resulting from transarterial embolization of a renal pseudoaneurysm secondary to percutaneous nephrostomy. Emergent transarterial embolization was required due to life-threatening active bleeding of the pseudoaneurysm. However, the glue material subsequently fell into the ureter where it became a foreign body, resulting in obstructive uropathy. Several surgical interventions, including endoscopic and laparoscopic methods, were performed to retrieve the foreign body, but these attempts were unsuccessful. Finally, the glue material was spontaneously passed out by chance. To the best of our knowledge, this type of complication (a glue particle left over from an embolization procedure migrating into the urinary collecting system) has never been reported. We recommend close follow-up examinations after transarterial embolization for renal pseudoaneurysm in order to avoid possible obstructive uropathy caused by glue materials or coils., (Copyright © 2012. Published by Elsevier B.V.)

We employ a microfluidic chip with three culture chambers to investigate the interactions among lung cancer cells, macrophages and myofibroblasts. By mixing the conditioned media of macrophages and myofibroblasts in this chip, we confirm that these two stromal cells have synergistic effects in accelerating the migration of cancer cells. However, as the myofibroblasts are pretreated with the conditioned medium of macrophages, the myofibroblasts' ability to enhance the migration of cancer cells is lowered. The tumour necrosis factor-α produced by macrophages reduces the expression of α-smooth muscle actin and the secretion of transforming growth factor-β1 in myofibroblasts. Once the tumour necrosis factor-α in the macrophage conditioned medium is neutralized, the macrophage medium-pretreated myofibroblasts can still accelerate the migration of cancer cells., (This journal is © The Royal Society of Chemistry 2012)

This study constructs a novel blood pressure measurement device without the air cuff to overcome the problem of discomfort and portability. The proposed device measures the blood pressure through a mechanism that is made of silicon rubber and pressure transducer. The system uses a microcontroller to control the measurement procedure and to perform the necessary computation. To verify the feasibility of the constructed device, ten young volunteers were recruited. Ten blood pressure readings were obtained using the new system and were compared with ten blood pressure readings from bedside monitor (Spacelabs Medical, model 90367). The results indicated that, when all the readings were included, the mean pressure, systolic pressure and diastolic pressure from the new system were all higher than those from bedside monitor. The correlation coefficients between these two were 0.15, 0.18 and 0.29, for mean, systolic and diastolic pressures, respectively. After excluding irregular apparatus utilization, the correlation coefficient increased to 0.71, 0.60 and 0.41 for diastolic pressure, mean pressure and systolic pressure, respectively. We can conclude from these results that the accuracy can be improved effectively by defining the user regulation more precisely. The above mentioned irregular apparatus utilization factors can be identified and eliminated by the microprocessor to provide a reliable blood pressure measurement in practical applications in the future.

Endopolyploidy is frequently observed during development in plant species. Patterns of endopolyploidy are diverse in the various organs of different plant species. However, little is known about the role of endopolyploidization and its significance in orchids. This study was undertaken to determine the extent of endopolyploidy in different tissues of the diploid and tetraploid genotypes of Phalaenopsis aphrodite subsp. formosana and to examine the factors that contribute to increased ploidy levels. Endopolyploidy occurs in various tissues of diploid and tetraploid orchids, at different developmental stages and under different culture conditions, as determined by flow cytometry. In this study, different patterns of endopolyploidy were observed in parts of the protocorms, leaves, roots and flowers. Endopolyploidy was found in all tissues studied except the pollinia and the tetraploid ovaries. A higher degree of endopolyploidy was observed in mature tissues compared to young tissues, greenhouse-grown plants compared to in vitro plants and diploid plants compared to tetraploid plants. We discuss the relationships between endopolyploidization and several factors related to plant growth, as well as some practical considerations of these findings., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We use a microfluidic cell culture chip equipped with pneumatic microvalves to analyze the paracrine loop between lung cancer cells and fibroblasts. In order to assess the cellular responses in the paracrine loop, we measure the migration speeds of cancer cells and the aspect ratios of fibroblasts which reflect the phenotype of myofibroblasts. With well-controlled interaction sequences between these two types of cells, we verify that the cytokines from cancer cells effectively stimulate the fibroblasts into myofibroblasts. The cytokines from myofibroblasts, rather than fibroblasts, increase the migration speeds of cancer cells. We confirm that the transforming growth factor-β1 (TGF-β1) is involved in the interaction between cancer cells and fibroblasts, and we also interrupt this paracrine loop in the cell culture chip by inhibiting the TGF-β1 receptors on fibroblasts., (© The Royal Society of Chemistry 2011)

Pharmacokinetics of free-form levobupivacaine (LB) and free-form racemic bupivacaine (BU) using microdialysis sampling technique were conducted in this study. Three microdialysis probes were implanted in the jugular vein toward the right atrium, brain striatum and bile duct of male Sprague-Dawley rats for concurrently sampling free drug. Effects of P-glycoprotein (P-gp) on the brain distribution and hepatobiliary excretion of LB and BU were examined for the first time after cyclosporine (CsA) administration. LB and BU in samples were determined by HPLC. The blood pharmacokinetics of free LB and free BU were not significantly different. For brain pharmacokinetics, the CsA pretreatment raised significantly the area under curve (AUC) of BU (24.0+/-5.9 vs. 14.6+/-4.4min microg/mL, p=0.015). Brain regions concentrations of LB and BU were significantly higher than plasma concentrations of LB (p<0.001) and BU (p<0.001), respectively. The BU concentration of cerebral cortex was significant higher than that of striatum (6.06+/-1.03 vs. 4.04+/-0.90microg/mL, p=0.005) and hippocampus (6.06+/-1.03 vs. 4.45+/-1.07microg/mL, p=0.04), suggesting that BU might display an uneven brain distribution. For bile pharmacokinetics, LB and BU went through hepatobiliary excretion, and the AUC of BU was significantly higher than that of the LB group (6.6+/-1.0 vs. 4.6+/-0.6min microg/mL, p=0.005). In addition, the pretreatment of CsA significantly reduced the hepatobiliary excretion of BU in terms of AUC (4.4+/-0.8 vs. 6.6+/-1.0minmicrog/mL, p=0.003). Furthermore, the maximum concentration (C(max)) of BU diminished significantly as a result of the CsA pretreatment (0.10+/-0.03 vs. 0.20+/-0.05microg/mL, p=0.002). To sum up, enantioselective brain distribution and hepatobiliary excretion of free LB and free BU were observed, and P-gp may relate to the drug transport., (Copyright 2010 Elsevier B.V. All rights reserved.)

Aberrant alternative splicing of key cellular regulators may play a pivotal role in cancer development. To investigate the potential influence of altered alternative splicing on the development of transitional cell carcinoma (TCC), splicing activity in the TCC cell lines TSGH8301 and BFTC905 was examined using the SV40-immortalized uroepithelial cell line SV-HUC-1 as a reference. Our results indicate a significant alteration in splice site selection in the TCC cell lines. By gene expression profiling and subsequent validation, we discovered that sex-determining region Y-box protein 2 (SOX2) is specifically upregulated in BFTC905. Furthermore, ectopic expression of SOX2 modulates alternative splicing of the splicing reporter in vivo. More significantly, using an in vitro pull-down assay, it was found that SOX2 exhibits RNA-binding capability. Our observations suggest that SOX2 modulates alternative splicing by functioning as a splicing factor., (2010 Elsevier Inc. All rights reserved.)

Urothelial cell carcinoma is the most common type of malignancy found in long-term dialysis patients and kidney transplant recipients in Taiwan. Surgical specimens of tumorous and non-tumorous bladder tissues were collected from 12 patients with bladder cancer. Increased expressions of Ras, RhoA, Akt, PI-3K were demonstrated in the tumors as compared to adjacent control tissues. To understand the impact of Ras over-expression on bladder cancer progression, human bladder cancer TSGH 8301 cells were transfected with Ras DNA. The Ras-transfected cells were then treated with either a PI-3K inhibitor (wortmannin) or Rho kinase inhibitor (Y-27632) and the expressions of Ras, PI-3K, Akt, NF-kappaB, and RhoA were analyzed. Fluorescent phalloidin staining demonstrated more intense F-actin staining in the Ras over-expressed cells than in the control cells, and the intensity of F-actin was inhibited by Y-27632. A gelatin zymography study demonstrated that the MMP-2 and MMP-9 expressions of the Ras-transfected cells were enhanced, and Y-27632 treatment reduced the levels of MMP-2 and MMP-9. Similarly, a wound healing assay revealed that the ability of cell migration was markedly increased by Ras transfection and the healing rate after treatment of Y-27632 was delayed. Our results provide evidence that Ras-induced RhoA and NF-kappaB activation was involved in the invasion/migration of bladder cancer. Through Ras and/or RhoA inhibition, there might be an opportunity for new therapeutic interventions in bladder cancer.

There is yet to be a reliable prediction of urolithiasis. To facilitate early diagnosis, a simple and rapid high performance liquid chromatography method with electrochemical detection using disposable copper-nanoparticle-plated electrodes (Cu(n)-SPE) was developed for multiple detection of creatinine and 4 urolithic organic acids. A total of 206 normal and urolithic human and canine urines and urolith samples were collected for direct analysis of creatinine, cystine, uric acid, oxalic acid, and citric acid without sample cleanup and derivatization processes. Urinary organic acids were separated in 11 min and were devoid of ascorbic acid interference. The detection limits (S/N>3) were at the nanomolar level with linear dynamic ranges spanning 2-3 orders of magnitude. Recoveries in urine ranged from 99.5% for creatinine to 86.5% for citric acid. The analytical variations (RSD) were less than 6.2% in phosphate buffer and 7.7% in urine. Important differences in organic acid levels/profiles between animal species and among normal and urolithic urines/urolith were unveiled and corresponded well (70-90%) with the urolithic risk in a retrospective assessment. The simplicity and reproducibility of this method using disposable Cu(n)-SPE has made routine urine analysis possible and can be of great clinical and diagnostic potential in the screening of urolithiasis and abnormal states related to excess secretion of organic acids and amino acids in humans and animals.

A clonal cell line, GBC4, derived from grouper (Epinephelus coioides) brain is proposed to represent an immature astroglial cell line because it expresses glial fibrillary acidic protein (GFAP), cytokeratin and vimentin. In teleost brain, tanycytes are the most abundant GFAP-expressing cell type, suggesting that GBC4 cells are derived from tanycytes. To test this hypothesis, protein and mRNA expression profiles of GBC4 cells were evaluated. We detected protein and/or mRNA expression of aromatase B, brain lipid binding protein, connexin43 protein, glutamine synthetase, S100 protein and Sox2. These proteins/mRNAs are also expressed in fish tanycytes. GBC4 cells also contained oligodendroglia proteins, including A2B5, galactocerebroside, myelin basic protein, proteolipid protein and platelet-derived growth factor receptor alpha as well as certain neuronal protein markers such as connexin35 protein and tyrosine hydroxylase. Our results indicate that GBC4 cells may be multipotent neural progenitor cells similar to tanycytes. Because GBC4 expresses several neural-specific genes, this line will be useful for studies on gene expression/regulation and neural development.

Splenogonadal fusion (SGF) is a rare congenital non-malignant anomaly characterized by fusion of splenic tissue to the gonad, and can be continuous or discontinuous. Very few cases have been diagnosed preoperatively, and many patients who present with testicular swelling undergo unnecessary orchiectomy under the suspicion of testicular neoplasm. A 16-year-old boy presented with a left scrotal mass and underwent total excision of a 1.6-cm tumor without damaging the testis, epididymis or its accompanying vessels. Pathologic examination revealed SFG (discontinuous type). If clinically suspected before surgery, the diagnosis may be confirmed by Tc-99m sulfur colloid imaging, which shows uptake in both the spleen and accessory splenic tissue within the scrotum. Frozen section should be considered if there remains any doubt regarding the diagnosis during operation.