Does knowledge of cancer diagnosis affect quality of life? A methodological challenge

BACKGROUND: As part of an assessment of quality of life in lung cancer patients an investigation was carried out to examine whether the knowledge of their diagnosis affected their quality of life. METHODS: Every patient in a defined geographical area with a potential diagnosis of lung cancer was interviewed at first consultation and after a definitive treatment has been given. Quality of life was assessed using three standard measures: the Nottingham Health Profile (NHP), the EORTC quality of life questionnaire (QLQ-C30) and its lung cancer supplementary questionnaire (QLQ-LC13). Comparison was made in quality of life scores between patients who knew their cancer diagnosis and those who did not. RESULTS: In all, 129 lung cancer patients were interviewed. Of these, 30 patients (23%) knew and 99 (78%) did not know their cancer diagnosis at the time of baseline assessment. The patient groups were similar in their characteristics except for age (P = 0.04) and cell type (P < 0.0001). Overall, there were no significant differences between these two groups with regard to their scores on the three instruments used. A major finding was that both group scored almost the same on emotional reactions (P = 0.8) and social isolation (P = 1.0) as measured by the NHP, and emotional (P = 0.7) and social functioning (P = 1.0) as measured by the EORTC QLQ-C30. In addition there were no significant differences in patients' symptom scores between those who knew their diagnosis and those who did not, nor did any consistent pattern emerge. The only significant difference was for sleep difficulties (P = 0.02). CONCLUSION: The findings suggest that the knowledge of cancer diagnosis does not affect the way in which patients respond to quality of life questionnaires

Methods for genetic manipulation of Burkholderia gladioli pathovar cocovenenans

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia gladioli </it>pathovar <it>cocovenenans </it>(BGC) is responsible for sporadic food-poisoning outbreaks with high morbidity and mortality in Asian countries. Little is known about the regulation of virulence factor and toxin production in BGC, and studies in this bacterium have been hampered by lack of genetic tools.</p> <p>Findings</p> <p>Establishment of a comprehensive antibiotic susceptibility profile showed that BGC strain ATCC33664 is susceptible to a number of antibiotics including aminoglycosides, carbapenems, fluoroquinolones, tetracyclines and trimethoprim. In this study, we established that gentamicin, kanamycin and trimethoprim are good selection markers for use in BGC. Using a 10 min method for preparation of electrocompetent cells, the bacterium could be transformed by electroporation at high frequencies with replicative plasmids containing the pRO1600-derived origin of replication. These plasmids exhibited a copy number of > 100 in BGC. When co-conjugated with a transposase expressing helper plasmid, mini-Tn<it>7 </it>vectors inserted site- and orientation-specifically at a single <it>glmS</it>-associated insertion site in the BGC genome. Lastly, a <it>Himar1 </it>transposon was used for random transposon mutagenesis of BGC.</p> <p>Conclusions</p> <p>A series of genetic tools previously developed for other Gram-negative bacteria was adapted for use in BGC. These tools now facilitate genetic studies of this pathogen and allow establishment of toxin biosynthetic pathways and their genetic regulation.</p

Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy

BACKGROUND: In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. METHODS: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. RESULTS: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. CONCLUSION: Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines

Trackways Produced by Lungfish During Terrestrial Locomotion

Some primarily aquatic vertebrates make brief forays onto land, creating traces as they do. A lack of studies on aquatic trackmakers raises the possibility that such traces may be ignored or misidentified in the fossil record. Several terrestrial Actinopterygian and Sarcopterygian species have previously been proposed as possible models for ancestral tetrapod locomotion, despite extant fishes being quite distinct from Devonian fishes, both morphologically and phylogenetically. Although locomotion has been well-studied in some of these taxa, trackway production has not. We recorded terrestrial locomotion of a 35 cm African lungfish (Protopterus annectens; Dipnoi: Sarcopterygii) on compliant sediment. Terrestrial movement in the lungfish is accomplished by planting the head and then pivoting the trunk. Impressions are formed where the head impacts the substrate, while the body and fins produce few traces. The head leaves a series of alternating left-right impressions, where each impact can appear as two separate semi-circular impressions created by the upper and lower jaws, bearing some similarity to fossil traces interpreted as footprints. Further studies of trackways of extant terrestrial fishes are necessary to understand the behavioural repertoire that may be represented in the fossil track record

Docking of LDCVs Is Modulated by Lower Intracellular [Ca2+] than Priming

Many regulatory steps precede final membrane fusion in neuroendocrine cells. Some parts of this preparatory cascade, including fusion and priming, are dependent on the intracellular Ca2+ concentration ([Ca2+]i). However, the functional implications of [Ca2+]i in the regulation of docking remain elusive and controversial due to an inability to determine the modulatory effect of [Ca2+]i. Using a combination of TIRF-microscopy and electrophysiology we followed the movement of large dense core vesicles (LDCVs) close to the plasma membrane, simultaneously measuring membrane capacitance and [Ca2+]i. We found that a free [Ca2+]i of 700 nM maximized the immediately releasable pool and minimized the lateral mobility of vesicles, which is consistent with a maximal increase of the pool size of primed LDCVs. The parameters that reflect docking, i.e. axial mobility and the fraction of LDCVs residing at the plasma membrane for less than 5 seconds, were strongly decreased at a free [Ca2+]i of 500 nM. These results provide the first evidence that docking and priming occur at different free intracellular Ca2+ concentrations, with docking efficiency being the most robust at 500 nM

Joint effect of phosphorus limitation and temperature on alkaline phosphatase activity and somatic growth in Daphnia magna

Alkaline phosphatase (AP) is a potential biomarker for phosphorus (P) limitation in zooplankton. However, knowledge about regulation of AP in this group is limited. In a laboratory acclimation experiment, we investigated changes in body AP concentration for Daphnia magna kept for 6 days at 10, 15, 20 and 25°C and fed algae with 10 different molar C:P ratios (95–660). In the same experiment, we also assessed somatic growth of the animals since phosphorus acquisition is linked to growth processes. Overall, non-linear but significant relationships of AP activity with C:P ratio were observed, but there was a stronger impact of temperature on AP activity than of P limitation. Animals from the lowest temperature treatment had higher normalized AP activity, which suggests the operation of biochemical temperature compensation mechanisms. Body AP activity increased by a factor of 1.67 for every 10°C decrease in temperature. These results demonstrate that temperature strongly influences AP expression. Therefore, using AP as a P limitation marker in zooplankton needs to consider possible confounding effects of temperature. Both temperature and diet affected somatic growth. The temperature effect on somatic growth, expressed as the Q10 value, responded non-linearly with C:P, with Q10 ranging between 1.9 for lowest food C:P ratio and 1.4 for the most P-deficient food. The significant interaction between those two variables highlights the importance of studying temperature-dependent changes of growth responses to food quality

Relapse patterns in NMOSD: evidence for earlier occurrence of optic neuritis and possible seasonal variation

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD