A Rare Case of Squamous Cell Carcinoma of the Bladder Presenting as a Metastatic Right Ventricular Mass

A 74-year-old woman presented with bilateral lower extremity swelling, worsening dyspnea on exertion, and mild hemoptysis. An echocardiogram at time of admission showed a mass in the right ventricle. The pathology of a sample obtained via transvenous biopsy was consistent with squamous cell carcinoma; no primary source could initially be identified. Severe thrombocytopenia, likely consumptive, precluded surgical intervention, so the patient underwent palliative radiation. Unfortunately, she developed fatal respiratory failure. Upon autopsy, the bladder was found to contain polyps of invasive squamous cell carcinoma, similar in morphology to the tumor mass in the heart. Her lungs contained multiple tumor emboli at different stages, which was likely the final cause of her death. Squamous cell carcinoma metastases to the endocardium are extremely rare and without defined treatment. Surgery can improve prognosis in those with primary tumors that are benign or without metastases. In those with symptomatic metastatic tumors, palliative debulking can done although generally will not improve prognosis. It is currently unknown whether radiation improves survival. In this case, irradiation did destroy a portion of the tumor as the final pathology showed extensive necrosis of the tumor; unfortunately, it did not change her symptoms and did not change the final outcome

Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands.

G-Quadruplex DNAs are folded, non-Watson-Crick structures that can form within guanine-rich DNA sequences such as telomeric repeats. Previous studies have identified a series of trisubstituted acridine derivatives that are potent and selective ligands for G-quadruplex DNA. These ligands have been shown previously to inhibit the activity of telomerase, the specialized reverse transcriptase that regulates telomere length. The RecQ family of DNA helicases, which includes the Bloom's (BLM) and Werner's (WRN) syndrome gene products, are apparently unique among cellular helicases in their ability to efficiently disrupt G-quadruplex DNA. This property may be relevant to telomere maintenance, since it is known that the sole budding yeast RecQ helicase, Sgs1p, is required for a telomerase-independent telomere lengthening pathway reminiscent of the "ALT" pathway in human cells. Here, we show that trisubstituted acridine ligands are potent inhibitors of the helicase activity of the BLM and WRN proteins on both G-quadruplex and B-form DNA substrates. Inhibition of helicase activity is associated with both a reduction in the level of binding of the helicase to G-quadruplex DNA and a reduction in the degree to which the G-quadruplex DNA can support DNA-dependent ATPase activity. We discuss these results in the context of the possible utility of trisubstituted acridines as antitumor agents for the disruption of both telomerase-dependent and telomerase-independent telomere maintenance

Impact of calcium on salivary α-amylase activity, starch paste apparent viscosity and thickness perception

Thickness perception of starch-thickened products during eating has been linked to starch viscosity and salivary amylase activity. Calcium is an essential cofactor for α-amylase and there is anecdotal evidence that adding extra calcium affects amylase activity in processes like mashing of beer. The aims of this paper were to (1) investigate the role of salivary calcium on α-amylase activity and (2) to measure the effect of calcium concentration on apparent viscosity and thickness perception when interacting with salivary α-amylase in starch-based samples. α-Amylase activity in saliva samples from 28 people was assessed using a typical starch pasting cycle (up to 95 °C). The activity of the enzyme (as measured by the change in starch apparent viscosity) was maintained by the presence of calcium, probably by protecting the enzyme from heat denaturation. Enhancement of α-amylase activity by calcium at 37 °C was also observed although to a smaller extent. Sensory analysis showed a general trend of decreased thickness perception in the presence of calcium, but the result was only significant for one pair of samples, suggesting a limited impact of calcium enhanced enzyme activity on perceived thickness

What limits supercurrents in high temperature superconductors? A microscopic model of cuprate grain boundaries

The interface properties of high-temperature cuprate superconductors have been of interest for many years, and play an essential role in Josephson junctions, superconducting cables, and microwave electronics. In particular, the maximum critical current achievable in high-Tc wires and tapes is well known to be limited by the presence of grain boundaries, regions of mismatch between crystallites with misoriented crystalline axes. In studies of single, artificially fabricated grain boundaries the striking observation has been made that the critical current Jc of a grain boundary junction depends exponentially on the misorientation angle. Until now microscopic understanding of this apparently universal behavior has been lacking. We present here the results of a microscopic evaluation based on a construction of fully 3D YBCO grain boundaries by molecular dynamics. With these structures, we calculate an effective tight-binding Hamiltonian for the d-wave superconductor with a grain boundary. The critical current is then shown to follow an exponential suppression with grain boundary angle. We identify the buildup of charge inhomogeneities as the dominant mechanism for the suppression of the supercurrent.Comment: 28 pages, 12 figure

Following a natural experiment of guideline adaptation and early implementation: a mixed-methods study of facilitation

<p>Abstract</p> <p>Background</p> <p>Facilitation is emerging as an important strategy in the uptake of evidence. However, it is not entirely clear from a practical perspective how facilitation occurs to help move research evidence into nursing practice. The Canadian Partnership Against Cancer, also known as the 'Partnership,' is a Pan-Canadian initiative supporting knowledge translation activity for improved care through guideline use. In this case-series study, five self-identified groups volunteered to use a systematic methodology to adapt existing clinical practice guidelines for Canadian use. With 'Partnership' support, local and external facilitators provided assistance for groups to begin the process by adapting the guidelines and planning for implementation.</p> <p>Methods</p> <p>To gain a more comprehensive understanding of the nature of facilitation, we conducted a mixed-methods study. Specifically, we examined the role and skills of individuals actively engaged in facilitation as well as the actual facilitation activities occurring within the 'Partnership.' The study was driven by and builds upon a focused literature review published in 2010 that examined facilitation as a role and process in achieving evidence-based practice in nursing. An audit tool outlining 46 discrete facilitation activities based on results of this review was used to examine the facilitation noted in the documents (emails, meeting minutes, field notes) of three nursing-related cases participating in the 'Partnership' case-series study. To further examine the concept, six facilitators were interviewed about their practical experiences. The case-audit data were analyzed through a simple content analysis and triangulated with participant responses from the focus group interview to understand what occurred as these cases undertook guideline adaptation.</p> <p>Results</p> <p>The analysis of the three cases revealed that almost all of the 46 discrete, practical facilitation activities from the literature were evidenced. Additionally, case documents exposed five other facilitation-related activities, and a combination of external and local facilitation was apparent. Individuals who were involved in the case or group adapting the guideline(s) also performed facilitation activities, both formally and informally, in conjunction with or in addition to appointed external and local facilitators.</p> <p>Conclusions</p> <p>Facilitation of evidence-based practice is a multifaceted process and a team effort. Communication and relationship-building are key components. The practical aspects of facilitation explicated in this study validate what has been previously noted in the literature and expand what is known about facilitation process and activity.</p

Lymph Node Negative Colorectal Cancers with Isolated Tumor Deposits Should Be Classified and Treated As Stage III

BACKGROUND: The prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients. MATERIALS AND METHODS: The medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated. RESULTS: Disease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P <.01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present. CONCLUSIONS: Because of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considere

Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial

Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma