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Objectives To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). Patients and methods Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients. Results The 3-year recurrence-free survival estimate for LN-positive NAC patients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients. Conclusion LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.

Social networking sites (SNSs) have increasingly become important tools for travelers to retrieve and share information related to their trips. The success of SNS marketing depends on users’ willingness to share information in SNS and intentions to build a social community with other users online. This study investigates the antecedents of travelers’ intention to participate in exchanging travel-related information on SNSs. A structural equation model reveals that trust and enjoyment plays as antecedents of intention to share travel information on SNSs whereas ease of use does not have a direct influence.

Reducing population salt intake is a global public health priority due to the potential to save lives and reduce the burden on the healthcare system through decreased blood pressure. This implementation science research project set out to measure salt consumption patterns and to assess the impact of a complex, multi-faceted intervention to reduce population salt intake in Fiji between 2012 and 2016. The intervention combined initiatives to engage food businesses to reduce salt in foods and meals with targeted consumer behavior change programs. There were 169 participants at baseline (response rate 28.2%) and 272 at 20 months (response rate 22.4%). The mean salt intake from 24-h urine samples was estimated to be 11.7 grams per day (g/d) at baseline and 10.3 g/d after 20 months (difference: -1.4 g/day, 95% CI -3.1 to 0.3, p = 0.115). Sub-analysis showed a statistically significant reduction in female salt intake in the Central Division but no differential impact in relation to age or ethnicity. Whilst the low response rate means it is not possible to draw firm conclusions about these changes, the population salt intake in Fiji, at 10.3 g/day, is still twice the World Health Organization's (WHO) recommended maximum intake. This project also assessed iodine intake levels in women of child-bearing age and found that they were within recommended guidelines. Existing policies and programs to reduce salt intake and prevent iodine deficiency need to be maintained or strengthened. Monitoring to assess changes in salt intake and to ensure that iodine levels remain adequate should be built into future surveys.

Background Urological survivorship issues encompass an area that may potentially be overlooked after treatment of childhood cancer in adolescent boys and young men. Side effects of cancer therapy may include subsequent development of erectile dysfunction (ED), hypogonadism, and infertility in adulthood. Aim The purpose of this review is to focus on the etiology and prevalence of the range of sexual and gonadal dysfunction in adolescent boys and young men who are cancer survivors, while discussing current recommendations for evaluation and treatment. Methods We performed a literature review of articles evaluating hypogonadism, sexual dysfunction, ED, and infertility in young men cancer survivors. Outcomes There is compelling evidence that significant survivorship issues are faced by boys entering adulthood after completing cancer therapy. Results Overall, young men cancer survivors are much more likely to report symptoms of sexual dysfunction than the general population of men. These patients can develop ED due to physiologic and psychological changes that take place with diagnosis of a malignancy and subsequent treatment. Primary hypogonadism can arise due to pelvic radiation or chemotherapy, and central hypogonadism may arise from pituitary insufficiency after brain radiation or surgery. Infertility develops from direct damage to the Sertoli cells and germinal epithelium from radiotherapy or chemotherapy. Cancer survivors who are men should therefore be screened for these important urological survivorship issues, although exact surveillance strategies remain unclear. Conclusions Urological survivorship issues including ED, hypogonadism, and infertility are common among cancer survivors and result in significant morbidity. Due to the medical complexity of cancer survivorship, the population of adolescent and young adult survivors would benefit from a network of multidisciplinary survivorship experts to aid the transition into adulthood. Improved research efforts may help to clarify risk factors and to develop enhanced strategies for evaluation and treatment. Sukhu T, Ross S, Coward RM. Urological Survivorship Issues Among Adolescent Boys and Young Men Who Are Cancer Survivors. Sex Med Rev 2018;6:396–409.

Background We evaluated the incidence and effect of thromboembolic events (TEEs) in patients with muscle-invasive bladder cancer treated with preoperative chemotherapy (POC) and radical cystectomy (RC) with pelvic lymph node dissection (PLND). Patients and Methods We performed a retrospective review of all patients who had undergone POC followed by RC plus PLND for muscle-invasive bladder cancer from June 2000 to January 2013 (n = 357). The chemotherapy type (neoadjuvant vs. induction), incidence and timing of TEE diagnosis (preoperatively vs. ≤ 90 days postoperatively), and effect of TEEs on clinical outcomes were recorded. Results Overall, 79 patients (22%; 95% confidence interval [CI], 18%-27%) experienced a TEE: 57 (16%) occurred during POC and 22 (6.2%) were diagnosed postoperatively. Forty patients (11%; 95% CI, 8.1%-15%) required an inferior vena cava filter. We found no significant differences in neoadjuvant versus induction chemotherapy and the risk of TEEs (difference, 3.3%; 95% CI, −5% to 12%; P = .5). No significant difference were found in the rates of POC completion according to the presence of a TEE (difference, 1.0%; 95% CI, −11% to 13%; P = .9). The occurrence of TEE did not significantly affect other perioperative outcomes. The risk of recurrence and overall survival were not associated with TEE on multivariable analysis. Conclusion We found a high incidence of TEEs (22%) in patients undergoing POC before RC plus PLND, with a 16% incidence in the preoperative period. TEEs in the POC setting leads to invasive procedures; however, we did not find a significant effect on POC completion or postoperative complication risk. Further research is required to determine whether preventative TEE measures during POC can improve clinical outcomes.

A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A Kinase Binding (AKB) domain of several AKAPs were chemically modified to contain an all-hydrocarbon staple and target the docking/dimerization domain of PKA-R, thereby occluding AKAP interactions. The peptides are cell-permeable against diverse human cell lines, are highly isoform-selective for PKA-RII, and can effectively inhibit interactions between AKAPs and PKA-RII in intact cells. These peptides can be applied as useful reagents in cell-based studies to selectively disrupt AKAP-localized PKA-RII activity and block AKAP signaling complexes. In summary, the novel hydrocarbon-stapled peptides developed in this study represent a new class of AKAP disruptors to study compartmentalized RII-regulated PKA signaling in cells.

Purpose or Research Questions: The purpose of this presentation is to investigate the feeding outcomes of mandibular distraction compared to tongue to lip adhesion in infants with Pierre Robin Sequence Background Pierre Robin Sequence (PRS) is a congenital disorder characterized by retroagnathia/micrognathia, glossoptosis, and respiratory distress and may result in a cleft palate. These craniofacial abnormalities cause significant difficulties with feeding and breathing during infancy and childhood. Though surgical intervention is a potential solution for this population, it can only be performed after a certain level of physical development has occurred, often referred to as the Rule of 10s. Children with PRS have difficulty getting the proper nutrition to optimize growth, especially in combination with breathing difficulties, which can result in failure to thrive. It is clinically important to determine the best practices for managing patients affected by craniofacial anomalies and swallowing disorders, including children with PRS who have a complex array of symptoms that impact feeding. Methods/Proposed Methods: The researchers used key terms relating to the disorder and population of choice to search across different databases focused on health science. Next, the researchers completed independent title and abstract reviews in order to exclude unrelated articles. After the title and abstract reviews, researchers performed full text and quality reviews of the remaining studies in order to finalize the data for evaluation. Results/Anticipated Results: The studies being evaluated have employed the use of mandibular distractors and tongue to lip adhesion techniques in order to improve respiration and feeding. In some instances, these interventions were ineffective and tube feeding was necessary to provide sufficient nourishment. A majority of the studies examined were conducted on smaller sample groups, due to the rarity of this condition in the general population. Quality appraisals and data extraction are in the process of being completed. Thus far, we have found that while these interventions provide adequate relief of respiratory distress in order to allow for oral feeding. Further data analysis is currently underway to determine if mandibular distraction or tongue to lip adhesion strategies provide the best outcomes for oral feeding and address feeding difficulties on a holistic level. Discussion (e.g., interpretation of results; potential contribution of anticipated results) Our anticipated results are based on multiple research studies with rather small sample groups. A majority of these studies were conducted using fewer than 50 participants, due to medical complexity of PRS and the relative rarity of studies, which look at patients with isolated PRS not occurring in conjunction with another syndrome and were conducted largely in hospitals with easy access to participants. These small, non-random samples may have skewed research findings in the direction of success for distractors, as they are most commonly used.

We present a detailed characterization of a single-cycle infection of the bocavirus minute virus of canines (MVC) in canine WRD cells. This has allowed identification of an additional smaller NS protein that derives from an mRNA spliced within the NS gene that had not been previously reported. In addition, we have identified a role for the viral NP1 protein during infection. NP1 is required for read-through of the MVC internal polyadenylation site and, thus, access of the capsid gene by MVC mRNAs. Although the mechanism of NP1's action has not yet been fully elucidated, it represents the first parvovirus protein to be implicated directly in viral RNA processing.

Overactive bladder (OAB) symptoms of urgency, frequency, and urge incontinence currently affect a substantial portion of the population, especially as age increases. Sacral neuromodulation has become a popular option for refractory OAB symptoms over the past 2 decades. Studies have demonstrated that it is an effective treatment for OAB and urge incontinence as indicated by decreased number of voids, increased bladder capacity, and fewer leakage events. In addition, the effects have proved to be durable to multiple years following implantation. These benefits come at the expense of a high rate of adverse events, although with comparable long-term cost-effectiveness to botulinum toxin A. We aimed to review the literature that demonstrates that sacral neuromodulation continues to be an efficacious treatment for refractory OAB wet and dry patients, with continuously expanding indications.

BACKGROUND: Because single-donor plateletpheresis concentrates now account for a large percentage of PLT concentrates, the PLT quality of individual donations is increasingly important. There has been little previous work on PLT function in blood donors. STUDY DESIGN AND METHODS: The aim of this study was to investigate the prevalence of defective PLT function among 100 healthy UK PLT donors on 3 consecutive donation days. Citrated blood samples were taken before plateletpheresis. High-shear PLT function testing was performed by a PLT function analyzer (PFA-100, Dade Behring), within both collagen-ADP (CADP) and collagen-epinephrine (CEPI) cartridges. RESULTS: Sixteen percent of PLT donors (mainly over the 3 donating days) had prolonged CEPI closure times (CTs) only, indicative of an aspirin-like pattern; 9 percent had a severe defect with prolonged CEPI CTs between 200 and 300 seconds, and 4 percent had maximal CEPI CTs of greater than 300 seconds. The majority of prolonged CEPI CTs appeared transient in nature. CONCLUSION: PLT dysfunction as detected by the PFA-100 is surprisingly common within a voluntary PLT donor population. The majority of CEPI defects appeared transient in nature and are indicative of surreptitious intake of cyclooxygenase inhibitors (e.g., aspirin). Identification of defective PLT function within donors would provide a simple means to eradicate defective PLTs from being clinically utilized.

significant in univariate analysis to identify predictors of perioperative (during hospital stay) morbidity and infection. Composite morbidity included hospital-acquired infection (13%) thrombotic (3.9%), renal (2.9%), ischemic (1%) or respiratory (1%) adverse events. Hospitalacquired infection included post-op infection (8.3%), Clostridium difficile (5.4%), sepsis (2%) and drug-resistant infection (0.05%). RESULTS: Similar to existing RCTs, with a cutoff of 21 days, we found no statistically significant difference in infection or morbidity. For 28 days, old blood independently predicted perioperative morbidity (HR 3.4 (1.5-8.5), p1⁄40.004). For 35 days, old blood independently predicted infection (HR 4.3 (1.4-12.8), p1⁄40.011), as well as morbidity (HR 6.2 (2.3-16.9), p1⁄40.0004). CONCLUSIONS: In conclusion, longer duration blood storage, especially 35 days, may be suboptimal and expose our bladder cancer patients to potential harm as demonstrated by increased morbidity and infectious complications in the post-operative setting.

This paper explores the male batterer's account of his violence based on a qualitative study of a sample of working class men, alleged batterers, conducted in Caribbean island of Trinidad demonstrating that the violence that they perform is integral to their masculine gender identity and that they take little or no responsibility for this violence. The findings are congruent with the international literature on the male account of battering which consistently reveals patterns of denial, minimization, excuses and justifications - tools through which the batterer may deny responsibility or accept limited responsibility for his violence. The paper also highlights the international and regional trends in responsibility in relation to masculinity and men's violence against known women particularly in the context of battering. In this study the complexity of the issue of responsibility in relation to local masculinities is further developed in the question of men taking responsibility for their violence against female intimate (ex)partners if not the men themselves.

Background: Little is known about the mechanisms and treatment of radiation-induced inhibition of craniofacial bone growth. In an earlier study, the radio-protector amifostine (WR-2721) administered to rabbits before irradiation radioprotected cultured orbitozygomatic complex periosteal osteoblast-like cells. This study assessed the effects of amifostine and its active metabolite on the radiation survival, function, and phenotype of mouse calvarial osteoblast-like cells in a cell culture model. Methods: MC3T3-E1 newborn mouse calvarial osteoblast-like cells underwent γ-radiation (0 to 10 Gy) in the presence or absence of either WR-2721 or WR-1065, its active metabolite (10 -7 to 10 -3 M). The effects of radiation with and without drugs were assessed using endpoints of colony-forming ability, cell viability, alkaline phosphatase activity, and expression of osteoblastic phenotype genes (alkaline phosphatase, collagen type I, osteocalcin, and osteopontin). All experiments were replicated at least in triplicate. Results: Irradiation resulted in a dose-dependent inhibition of clonogenic cell survival. Pretreatment with WR-1065, but not WR-2721, resulted in a significant improvement of osteoblast-like cell survival. Specifically, maximum radioprotection was observed with 10 -4 M WR-1065 at a clinically relevant 2-Gy dose of irradiation. No significant radioprotection was observed at the lower (5 X 10 -7 M) concentration of WR-1065. Furthermore, radiation seemed to suppress the expression of ostecblastic phenotype-related genes in a dose-dependent manner. Conclusions: This study reveals improved survival after irradiation in osteoblast-like cells treated with WR-1065 in vitro and corroborates previous findings from animal models. Further studies using this agent and similar drugs are important for devising strategies to prevent radiation-induced inhibition of craniofacial bone growth.

The use of d-dimer tests for the exclusion of venous thromboembolism is an important advance in clinical practice and also has economic benefits. The Stalia D-Di (Diagnostica Stago, Asnieres, France) is a semi automated system for the quantification of d-dimer using an immuno-turbidometric method incorporating a suspension of latex microparticles coated with two different monoclonal antibodies specifically targeted against human d-dimer fragments. Results are available rapidly in10 min compared with 35 min for the established VIDAS D-dimer automated enzyme-linked immunosorbent assay (ELISA, BioMerieux, Basingstoke, UK). During November and December 2005, 100 consecutive patients attending the outpatient deep venous thrombosis (DVT) clinic were tested using the VIDAS D-dimer as part of the routine DVT investigation. Using the same samples, D-dimer estimation was also performed on the STalia D-Di for comparison. Across a wide range of data (Vidas 83-5656) and (STali200-4000), there was good agreement between the two methods. Using cutoff's of 500 microg/l fibrinogen equivalent units (Keeling et al., 1999), 42% (42/100) patients were negative (500) and 46% (46/100) were positive (500) on both systems. Six per cent (6/100) were positive on the Vidas but negative on the STalia and another 6% (6/100) were positive on the STalia but negative on the Vidas. In conclusion, 88% (88/100) of patients showed agreement and in the other 12% (12/100), one had a DVT as identified by Compression ultrasonography (CUS). In this study, there were seven patients with a DVT as identified by CUS and they all scored as 'likely' on a pretest clinical probability score and so negative D-dimer would not be used clinically to rule out the disease. The Vidas is a well established instrument for D-dimer measurement in outpatient DVT clinics, and in this small study the STalia compares very well and therefore would fit into an outpatient setting for D-dimer measurement. But ideally a larger study would be required before implementing new methodology in a clinical setting.

Presence of lymph node metástasis (LNM) at salvage radical prostatectomy (sRP) is associated with poor outcome. Predictors of outcome in this context remain undetermined. ThE objective was to assess the role of number of positive lymph node on outcome of patients with LNM after sRP and for radio-recurrent prostate cancer.We analyzed data from a consecutive cohort of 215 men treated with sRP at a single institution. We used univariate Cox proportional hazard regression models for biochemical recurrence (BCR) and metastatic outcomes, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, time between radiation therapy and sRP, and number of positive nodes as predictors.Of the 47 patients with LNM, 37 developed BCR, 11 developed distant metastasis and 4 died with a median follow-up of 2.3 years for survivors. The risk of metastases increased with higher pre-operative PSA levels (HR 1.19 per 1ng/ml; 95% CI: 1.06-1.34; P=.003). The remaining predictors did not reach conventional levels of significance. However, removal of 3 or more positive lymph nodes demonstrated a positive association, as expected, with metastatic disease (HR 3.44; 95% CI: 0.91-13.05; P=.069) compared to one or 2 positive nodes. Similarly, the presence of extraprostatic extension, seminal vesicle invasion and Gleason grade greater than 7 also demonstrated a positive association with higher risk of metástasis, with hazard ratios of 3.97 (95% CI: 0.50, 31.4; P=.2), 3.72 (95% CI: 0.80-17.26; P=.1), and 1.45 (95% CI: 0.44-4.76; P=.5), respectively.In patients with LNM after sRP for radio-recurrent prostate cancer, the risk of distant metástasis is likely to be influenced by the number of positive nodes (3 or more), high preoperative PSA, Gleason grade and advanced pathologic stage. These results are consistent with the findings of number of nodes (1 to 2 vs. 3 or more nodes positive) as a prognostic indicator after primary radical prostatectomy and strengthen the plea for a revision of the nodal staging for prostate cancer.

Golgi beta1,6-N-acetylglucosaminyltransferase V (Mgat5) produces beta1,6GlcNAc-branched N-glycans on glycoproteins, which increases their affinity for galectins and opposes loss from the cell surface to constitutive endocytosis. Oncogenic transformation increases Mgat5 expression, increases beta1,6GlcNAc-branched N-glycans on epidermal growth factor and transforming growth factor-beta receptors, and enhances sensitivities to ligands, cell motility, and tumor metastasis. Here, we demonstrate that Mgat5(-/-) mouse embryonic fibroblasts (MEFs) display reduced sensitivity to anabolic cytokines and reduced glucose uptake and proliferation. Mgat5(-/-) mice are also hypoglycemic, resistant to weight gain on a calorie-enriched diet, hypersensitive to fasting, and display increased oxidative respiration and reduced fecundity. Serum-dependent activation of the extracellular response kinase (growth) and Smad2/3 (arrest) pathways in Mgat5(-/-) MEFs and bone marrow cells reveals an imbalance favoring arrest. Mgat5(-/-) mice have fewer muscle satellite cells, less osteogenic activity in bone marrow, and accelerated loss of muscle and bone mass with aging. Our results suggest that beta1,6GlcNAc-branched N-glycans promote sensitivity to anabolic cytokines, and increase fat stores, tissue renewal, and longevity.