Updates in intravesical electromotive drug administration(A (R)) of mitomycin-C for non-muscle invasive bladder cancer

Electromotive drug administration(A (R)) (EMDA) increases the local drug efficacy by controlling and enhancing transmembranous transport into tissue. EMDA of intravesical mitomycin-C (MMC) has been used for treatment of non-muscle invasive bladder cancer (NMIBC) for about a decade on the basis of laboratory studies that demonstrated an enhanced administration rate of MMC into all bladder wall layers after EMDA compared to standard instillation/passive diffusion (PD). Higher MMC concentrations might have a clinical impact since EMDA was associated with lower recurrence rates than PD in randomized studies. Further data suggest that EMDA/MMC is at least equivalent to BCG in treatment of high-risk bladder tumours. In addition, BCG combined with EMDA/MMC as well as preoperative EMDA/MMC are new therapeutic strategies with promising preliminary results in terms of higher remission rates and longer remission times. In summary, these findings suggest that EMDA for MMC delivery in the bladder could be a major therapeutic breakthrough in the treatment of NMIBC

Seabird bycatch in New Zealand trawl and longline fisheries, 1998-2004

Fisheries bycatch is a threatening process for populations of procellariiform seabirds, and is of particular importance for the conservation of albatross, an especially threatened group at a global scale. There is a high level ofendemism of albatross and petrels in New Zealand waters, and around one-third of the world's species of procellariiform seabirds breed in this area. Therefore, understanding the levels of mortality of these species in the New Zealand Exclusive Economic Zone is important for global conservation of the order. For New Zealand fisheries for the 1998-2004 fishing years, we estimated total seabird bycatch using data from scientific observers with model-based estimation procedures. Although sectors of the fishing activity were not evenly covered by observers, we were able to estimate seabird bycatch for large scale fisheries by vessel size (split at 28 m length), season, area and year. Approximately 5500 seabirds (credible interval between 2000 and 10 000) are estimated to be landed in New Zealand trawl and longline fisheries annually, as a result of interactions with fishing gear. Few data were available for the small vessels, thus estimates are highly uncertain. Mortalities are likely to be most common in trawl fisheries at approximately 2000-3000 seabirds annually, with the greatest contribution coming from large vessels. Around one half of these birds were albatross. For large surface longline vessels we estimated that fewer than 500 seabirds were killed annually during the main tuna fishing season. For large demersal vessels, seabird mortality was estimated to have decreased from around 1800 seabirds in 2001 to 600 seabirds in 2004. We report observed captures by species for each fishing method and area for the fishing years 1998-2004. Thirty-one species of Procellariiformes were identified during this period, over half of which are threatened species. For some species, such as White-chinned Petrel, Procellaria aequinoctialis and White-capped Albatross, 1halassarche steadi, several hundred individuals were caught. For 15 species, fewer than 10 individuals were identified. However, the unrepresentative deployment ofobserver coverage across fishery areas makes it difficult to interpret the conservation implications of species captures. A high proportion of the petrel species was observed caught primarily from areas surrounding their breeding sites while albatross were caught across breeding and non-breeding areas. Greatly improved observer sampling ratios, and studies of population status and trends, are needed to understand the conservation implications of the effects of New Zealand trawl and longline fishing mortalities on seabird populations

Social problem solving in carers of young people with a first episode of psychosis: A randomized controlled trial

"Brief report

Therapeutic strategies utilising SDF-1α in ischaemic cardiomyopathy

Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilise and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium. These effects have beneficial effects on infarct size, and left ventricular remodelling and function. However, the timing of endogenous SDF-1α release and CXCR4 upregulation may not be optimal. Furthermore, current ELISA-based assays cannot distinguish between active SDF-1α, and SDF-1α inactivated by dipeptidyl peptidase 4 (DPP4). Current therapeutic approaches aim to recruit the SDF-1α-CXCR4 pathway or prolong SDF-1α life-time by preventing its cleavage by DPP4. This review assesses the evidence supporting these approaches and proposes SDF-1α as an important confounder in recent studies of DPP4 inhibitors

Stack and Queue Layouts via Layered Separators

It is known that every proper minor-closed class of graphs has bounded stack-number (a.k.a. book thickness and page number). While this includes notable graph families such as planar graphs and graphs of bounded genus, many other graph families are not closed under taking minors. For fixed $g$ and $k$, we show that every $n$-vertex graph that can be embedded on a surface of genus $g$ with at most $k$ crossings per edge has stack-number $\mathcal{O}(\log n)$; this includes $k$-planar graphs. The previously best known bound for the stack-number of these families was $\mathcal{O}(\sqrt{n})$, except in the case of $1$-planar graphs. Analogous results are proved for map graphs that can be embedded on a surface of fixed genus. None of these families is closed under taking minors. The main ingredient in the proof of these results is a construction proving that $n$-vertex graphs that admit constant layered separators have $\mathcal{O}(\log n)$ stack-number.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemothera-peutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community

Localised prostate cancer and hemophilia A (AHA): Case report and management of the disease.

Acquired Hemophilia A (AHA) is a rare bleeding diathesis characterized by the development of autoantibodies against factor VIII (FVIII). About half of the cases are idiopathic and the other half are associated with autoimmune diseases, postpartum problems, infections, inflammatory bowel disease, drugs, lymphoproliferative disorders or solid tumors . AHA is associated with malignancies in 7-15% of cases. We report a case of AHA in a 65 year old patient with prostatic carcinoma, who underwent retropubic radical prostatectomy (RP)

A novel recombinant antibody specific to full-length stromal derived factor-1 for potential application in biomarker studies

Background: Stromal derived factor-1α (SDF-1α/CXCL12) is a chemokine that is up-regulated in diseases characterised by tissue hypoxia, including myocardial infarction, ischaemic cardiomyopathy and remote ischaemic conditioning (RIC), a technique of cyclical, non-injurious ischaemia applied remote from the heart that protects the heat from lethal ischaemia-reperfusion injury. Accordingly, there is considerable interest in SDF-1α as a potential biomarker of such conditions. However, SDF-1α is rapidly degraded and inactivated by dipeptidyl peptidase 4 and other peptidases, and the kinetics of intact SDF-1α remain unknown. Methods & results: To facilitate investigation of full-length SDF-1α we established an ELISA using a novel recombinant human antibody we developed called HCI.SDF1. HCI.SDF1 is specific to the N-terminal sequence of all isoforms of SDF-1 and has a comparable KD to commercially available antibodies. Together with a detection antibody specific to the α-isoform, HCI.SDF1 was used to specifically quantify full-length SDF-1α in blood for the first time. Using RIC applied to the hind limb of Sprague-Dawley rats or the arms of healthy human volunteers, we demonstrate an increase in SDF-1α using a commercially available antibody, as previously reported, but an unexpected decrease in full-length SDF-1α after RIC in both species. Conclusions: We report for the first time the development of a novel recombinant antibody specific to fulllength SDF-1. Applied to RIC, we demonstrate a significant decrease in SDF-1α that is at odds with the literature and suggests a need to investigate the kinetics of full-length SDF-1α in conditions characterised by tissue hypoxia

The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE To evaluate the efficacy and safety of duloxetine hydrochloride in the treatment of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS Thirty-eight CP/CPPS patients completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-Erectile Function-5 (IIEF-5) questionnaires, uroflowmetry, and evaluation of psychologic status using Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). Patients were randomly assigned to 2 treatments groups. Treatment in group 1 consisted of a simultaneous oral administration of tamsulosin (0.4 mg/d, 60 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d). Treatment in group 2 consisted of tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). NIH-CPSI and IIEF-5 questionnaires, uroflowmetry, and evaluation of the psychological status were repeated at 16 weeks of follow-up. RESULTS At 16 weeks, a significant improvement in NIH-CPSI pain subscore, NIH-CPSI quality of life subscore, and NIH-CPSI total score were observed in group 1 patients compared with those in group 2 (P <.01, respectively), together with a significant improvement in HAM-A and HAM-D scores (P <.01, respectively). Patients in group 2 showed a significant improvement in NIH-CPSI total score, in the urinary symptoms subscore, and in the HAM-A total score. No significant differences were observed in IIEF-5 scores in the 2 groups. Maximum flow rate significantly increased in both groups. In group 1, 20% of patients stopped the study due to adverse effects. CONCLUSION The use of duloxetine in a multimodal treatment with an alpha-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychologic status and quality of life patients affected by CP/CPPS