Death anxiety predicts fear of Cancer recurrence and progression in ovarian Cancer patients over and above other cognitive factors.

Death anxiety is understudied in people with cancer, especially in relation to fear of cancer recurrence (FCR) and fear of progression (FOP). The present study aimed to identify if death anxiety can predict FCR and FOP over and above other known theoretical predictors. One hundred and seventy-six participants with ovarian cancer were recruited for an online survey. We included theoretical variables, such as metacognitions, intrusive thoughts about cancer, perceived risk of recurrence or progression, and threat appraisal, in regression analyses to predict FCR or FOP. We investigated whether death anxiety added to the variance over and above these variables. Correlational analyses demonstrated that death anxiety is more strongly associated with FOP than FCR. The hierarchical regression including the theoretical variables described above predicted 62-66% of variance in FCR and FOP. In both models, death anxiety predicted a small but statistically significant unique variance in FCR and FOP. These findings draw attention to the importance of death anxiety in understanding FCR and FOP in people with a diagnosis of ovarian cancer. They also suggest that elements of exposure and existentialist therapies may be relevant in treating FCR and FOP.

The One-Stop Aortic Surveillance Clinic.

BACKGROUND: The principle of interval ultrasound surveillance of small abdominal aortic aneurysms (AAA) is well established. The fundamental principle of surveillance is that repair of AAA is a serious undertaking and the risk of the operation outweighs the risk of rupture in aneurysms less than 5.5 cm. Surveillance is well established but requires multiple visits to both the surgical clinic and the ultrasound department. REPORT: This report presents a system whereby the vascular surgeon is trained in the process of aortic sonography with a view to one-stop clinic assessment. After training of the main investigators in aortic sonography, the surgeons performed scans on the aortas of 80 consecutive patients and compared the scan result with the subsequent formal scan. DISCUSSION: Surgical and radiographer scans correlate very closely. It is believed that the one-stop aortic surveillance model is safe, accurate, and improves both the patient journey and clinic throughput.

Microcirculation in the foot is augmented by neuromuscular stimulation via the common peroneal nerve in different lower limb postures: a potential treatment for leg ulcers.

OBJECTIVES: To examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. STUDY DESIGN: Cross-sectional, healthy cohort, open label, physiological response study. METHODS: In 10 healthy volunteers, aged 19 to 24 years, Laser Doppler Fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive Geko device. RESULTS: The geko™ device was effective in increasing microcirculation on the dorsum of the foot in all four postures (Mean difference =141%, 95% CI 70%-212%, p=0.001). This effect was more pronounced than that of using a plaster alone (Mean increase in Flux of 73%, 95% CI 22%-125%, p=0.01) or variances due to the hydrostatic effects of different postures (Mean difference 17-27.6%, p>0.05). There was a 2 to 3 fold increase in flux when stimulation was delivered in combination with the plaster cast. CONCLUSIONS: Stimulation using the geko™ device augments microcirculation in the foot. The response is greater in lying and non-weight bearing than weight bearing standing but the most striking effect is when stimulation is combined with a plaster cast. The geko™ offers a potential means of promoting conditions favourable for wound healing, where treatment using compression may be contraindicated, such as arterial/mixed aetiology ulcers.

Microcirculation in the foot is augmented by neuromuscular stimulation via the common peroneal nerve in different lower limb postures: a potential treatment for leg ulcers.

AIM: Aim of the study was to examine the effects of the geko™ device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. METHODS: This was a cross-sectional, healthy cohort, open label, physiological response study. In 10 healthy volunteers, aged 19 to 24 years, laser Doppler fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the geko™ device applied over the common peroneal nerve, at 1 Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive geko™ device. RESULTS: The geko™ device was effective in increasing microcirculation on the dorsum of the foot in all four postures (mean difference =141%, 95% CI 70%-212%, P=0.001). This effect was more pronounced than that of using a plaster alone (Mean increase in flux of 73%, 95% CI 22%-125%, P=0.01) or variances due to the hydrostatic effects of different postures (mean difference 17-27.6%, P>0.05). There was a 2 to 3 fold increase in flux when stimulation was delivered in combination with the plaster cast. CONCLUSION: Stimulation using the geko™ device augments microcirculation in the foot. The response is greater in lying and non-weight bearing than weight bearing standing but the most striking effect is when stimulation is combined with a plaster cast. The geko™ offers a potential means of promoting conditions favourable for wound healing, where treatment using compression may be contraindicated, such as arterial/mixed aetiology ulcers.

Neuromuscular electrostimulation viathe common peroneal nerve promotes lower limb blood flow in a below-kneecast: A potential for thromboprophylaxis.

OBJECTIVES: We aimed to examine the characteristics of deep venous flow in the leg in a cast and the effects of a wearable neuromuscular stimulator (geko; FirstKind Ltd) and also to explore the participants' tolerance of the stimulator. METHODS: This is an open-label physiological study on ten healthy volunteers. Duplex ultrasonography of the superficial femoral vein measured normal flow and cross-sectional area in the standing and supine positions (with the lower limb initially horizontal and then elevated). Flow measurements were repeated during activation of the geko stimulator placed over the peroneal nerve. The process was repeated after the application of a below-knee cast. Participants evaluated discomfort using a questionnaire (verbal rating score) and a scoring index (visual analogue scale). RESULTS: The geko device was effective in significantly increasing venous blood flow in the lower limb both with a plaster cast (mean difference 11.5 cm/sec(-1); p = 0.001 to 0.13) and without a plaster cast (mean difference 7.7 cm/sec(-1); p = 0.001 to 0.75). Posture also had a significant effect on peak venous blood flow when the cast was on and the geko inactive (p = 0.003 to 0.69), although these differences were less pronounced than the effect of the geko (mean difference 3.1 cm/sec(-1) (-6.5 to 10)). The geko device was well tolerated, with participants generally reporting only mild discomfort using the device. CONCLUSION: The geko device increases venous blood flow in the lower limb, offering a potential mechanical thromboprolylaxis for patients in a cast. Cite this article: Bone Joint Res 2013;2:179-85.

Nitrogen isotopes as indicators of NO(x) source contributions to atmospheric nitrate deposition across the midwestern and northeastern United States.

Global inputs of NO(x) are dominated by fossil fuel combustion from both stationary and vehicular sources and far exceed natural NO(x) sources. However, elucidating NO(x) sources to any given location remains a difficult challenge, despite the need for this information to develop sound regulatory and mitigation strategies. We present results from a regional-scale study of nitrogen isotopes (delta15N) in wet nitrate deposition across 33 sites in the midwestern and northeastern U.S. We demonstrate that spatial variations in delta15N are strongly correlated with NO(x) emissions from surrounding stationary sources and additionally that delta15N is more strongly correlated with surrounding stationary source NO(x) emissions than pH, SO4(2-), or NO3- concentrations. Although emission inventories indicate that vehicle emissions are the dominant NO(x) source in the eastern U.S., our results suggest that wet NO3- deposition at sites in this study is strongly associated with NO(x) emissions from stationary sources. This suggests that large areas of the landscape potentially receive atmospheric NO(y) deposition inputs in excess of what one would infer from existing monitoring data alone. Moreover, we determined that spatial patterns in delta15N values are a robust indicator of stationary NO(x) contributions to wet NO3- deposition and hence a valuable complement to existing tools for assessing relationships between NO3- deposition, regional emission inventories, and for evaluating progress toward NO(x) reduction goals.

Anticoagulation, bleeding and blood transfusion practices in Australasian cardiac surgical practice.

We surveyed contemporary Australasian cardiac surgical and anaesthetic practice, focusing on antiplatelet and antifibrinolytic therapies and blood transfusion practices. The cohort included 499 sequential adult cardiac surgical patients in 12 Australasian teaching hospitals. A total of 282 (57%) patients received red cell or component transfusion. The median (IQR) red cell transfusion threshold haemogloblin levels were 66 (61-73) g/l intraoperatively and 79 (74-85) g/l postoperatively. Many (40%) patients had aspirin within five days of surgery but this was not associated with blood loss or transfusion; 15% had clopidogrel within seven days of surgery. In all, 30 patients (6%) required surgical re-exploration for bleeding. Factors associated with transfusion and excessive bleeding include pre-existing renal impairment, preoperative clopidogrel therapy, and complex or emergency surgery. Despite frequent (67%) use of antifibrinolytic therapy, there was a marked variability in red cell transfusion rates between centres (range 17 to 79%, P < 0.001). This suggests opportunities for improvement in implementation of guidelines and effective blood-sparing interventions. Many patients presenting for surgery receive antiplatelet and/or antifibrinolytic therapy, yet the subsequent benefits and risks remain unclear.

Evaluation of mattresses using interface pressure mapping.

OBJECTIVE: To compare the ranking of mattresses using several different performance indices, calculated from interface pressure-mapping data. METHOD: Five mattresses were compared using interface pressure-mapping on 10 healthy volunteers. Mattresses were ranked in order, on the basis of several different specified performance indices. RESULTS: Different performance indices ranked the mattresses in different orders. CONCLUSION: Elaborate performance indices should be used with care, since it is possible to construct a 'tailor-made' performance index to make any chosen mattress rank as the best. Care should be taken to ensure that a performance index is validated, preferably by some demonstrated link to clinical outcomes.

Chlamydial genovar distribution after community wide antibiotic treatment.

Major outer membrane protein sequences, determined from Chlamydia-positive eye swab samples collected in 2 Egyptian villages, were used to analyze the epidemiology of trachoma in an endemic setting. Samples were collected during the 1999 Azithromycin in Control of Trachoma trial, in which residents of villages were mass treated with either oral azithromycin or topical tetracycline and were followed up for nearly 2 years. Three genovar families (A, Ba, and C) and 12 genovars were detected, with 2 genovars (A1 and Ba1) comprising almost 75% of the samples. The presence of >1 genovar within households was common, with > or =24% of households having >1 genovar. Evidence consistent with reinfection and persistence as mechanisms of communitywide continued presence of trachoma was provided by data for individuals infected with rare genovars.

Feline leukemia virus DNA vaccine efficacy is enhanced by coadministration with interleukin-12 (IL-12) and IL-18 expression vectors.

The expectation that cell-mediated immunity is important in the control of feline leukemia virus (FeLV) infection led us to test a DNA vaccine administered alone or with cytokines that favored the development of a Th1 immune response. The vaccine consisted of two plasmids, one expressing the gag/pol genes and the other expressing the env gene of FeLV-A/Glasgow-1. The genetic adjuvants were plasmids encoding the feline cytokines interleukin-12 (IL-12), IL-18, or gamma interferon (IFN-gamma). Kittens were immunized by three intramuscular inoculations of the FeLV DNA vaccine alone or in combination with plasmids expressing IFN-gamma, IL-12, or both IL-12 and IL-18. Control kittens were inoculated with empty plasmid. Following immunization, anti-FeLV antibodies were not detected in any kitten. Three weeks after the final immunization, the kittens were challenged by the intraperitoneal inoculation of FeLV-A/Glasgow-1 and were then monitored for a further 15 weeks for the presence of virus in plasma and, at the end of the trial, for latent virus in bone marrow. The vaccine consisting of FeLV DNA with the IL-12 and IL-18 genes conferred significant immunity, protecting completely against transient and persistent viremia, and in five of six kittens protecting against latent infection. None of the other vaccines provided significant protection.

The practice characterization model: the importance of organizational life cycles and targeted interventions in general medical practice.

In response to a climate of constant change and increasing demand for services, general practice in the UK has undergone significant modification over the last 10 years. It has become a multi-disciplinary organisation encouraged by funding bodies to plan for service delivery using a more structured team based approach. In Tayside in 1996, practices were charged with producing formal Practice Development Plans (PDPs) which would focus on priority areas aligned with the Health Boards own strategic plan--those were teamwork, information management and technology, and clinical service delivery. The University of Dundee's Department of General Practice successfully applied for funding to develop ways of facilitating practices so that they could a) identify their own development priorities, and b) plan and implement action and learning to see these priorities through. Using action research methodology, the project attempted to create a climate for change, provide support and training to see the changes implemented, and ensure commitment to the changes from all members of the practice team. The Facilitator adopted a flexible style varying her role between expert, guide and support. Analysis of progress made by different practices, coupled with the Facilitator's in depth knowledge of them, suggested the importance of certain key aspects of practice organisation and culture. A practice characterisation model identified practices which were stable, currently coping, proactive and ready to face the challenge of change as best placed to engage in a full scale development programme. Other profiles suggested a range of alternative interventions as more likely to be acceptable and productive.

Knowledge of and attitudes toward the pill: results of a national survey in Japan.

CONTEXT: After decades of debate, the oral contraceptive pill was legalized in Japan in June 1999. Because the pill had been unavailable up until then, little is known about the public's knowledge about, attitudes toward and intentions to use the pill. METHODS: In a nationwide probability sample, 630 women and men were interviewed in their homes in March 1999. Respondents were asked a range of questions to gauge their knowledge about and attitudes toward the pill. RESULTS: Most respondents (79%) could identify both the name and purpose of the birth control pill. Roughly the same proportion of respondents held an overall positive impression (44%) as held a negative impression (42%) of the pill, and 14% were undecided about the method. The pill's high level of effectiveness in pregnancy prevention was the most common reason for having a favorable impression of it (47%). Women were more concerned about side effects than were men, and they also knew more about the pill's potential side effects than did men. Only 12% of respondents said they intended to use the pill if it were approved. Roughly one-quarter (23-26%) did not correctly identify the pill's inability to protect against HIV and other sexually transmitted diseases (STDs). CONCLUSIONS: Legalization of oral contraceptives in Japan has led to an urgent need to educate both men and women on the inability of the pill to protect against STDs, including HIV Policymakers and providers need to recognize the importance of encouraging dual method use in Japan.

The N-terminal region of human progesterone B-receptors: biophysical and biochemical comparison to A-receptors.

To understand the basis for functional differences between the two human progesterone receptors (PR), we have carried out a detailed biochemical and biophysical analysis of the N-terminal region of each isoform. Extending our previous work on the A-isoform (Bain, D. L, Franden, M. A., McManaman, J. L., Takimoto, G. S., and Horwitz, K. B. (2000) J. Biol. Chem. 275, 7313-7320), here we present studies on the N-terminal region of the B-isoform (NT-B) and compare its properties to its A-receptor counterpart (NT-A). As seen previously with NT-A, NT-B is quantitatively monomeric in solution, yet undergoes N-terminal-mediated assembly upon DNA binding. Limited proteolysis, microsequencing, and sedimentation analyses indicate that the B-isoform exists in a non-globular, extended conformation very similar to that of NT-A. Additionally, the 164 amino acids unique to the B-isoform (BUS) appear to be in a more extended conformation relative to sequences common to both receptors and do not exist as an independent structural domain. However, sedimentation studies of NT-A and NT-B show differences in the ensemble distribution of their conformational states. We hypothesize that isoform-specific functional differences are not due to structural differences, per se. Rather, the transcriptional element BUS, or possibly other transcription factors, causes a redistribution of the conformational ensemble by stabilizing a more functionally active set of conformations in NT-B.

Biophysical characterization of the DNA binding domain of gpNu1, a viral DNA packaging protein.

Terminase enzymes are common to double-stranded DNA viruses. These enzymes "package" the viral genome into a pre-formed capsid. Terminase from bacteriophage lambda is composed of gpA (72.4 kDa) and gpNu1 (20.4 kDa) subunits. We have described the expression and biochemical characterization of gpNu1DeltaK100, a construct comprising the N-terminal 100 amino acids of gpNu1 (Yang, Q., de Beer, T., Woods, L., Meyer, J., Manning, M., Overduin, M., and Catalano, C. E. (1999) Biochemistry 38, 465-477). Here we present a biophysical characterization of this construct. Thermally induced loss of secondary and tertiary structures is fully reversible. Surprisingly, although loss of tertiary structure is cooperative, loss of secondary structure is non-cooperative. NMR and limited proteolysis data suggest that approximately 30 amino acids of gpNu1DeltaK100 are solvent-exposed and highly flexible. We therefore constructed gpNu1DeltaE68, a protein consisting of the N-terminal 68 residues of gpNu1. gpNu1DeltaE68 is a dimer with no evidence of dissociation or further aggregation. Thermally induced unfolding of gpNu1DeltaE68 is reversible, with concomitant loss of both secondary and tertiary structure. The melting temperature increases with increasing protein concentration, suggesting that dimerization and folding are, at least in part, coupled. The data suggest that gpNu1DeltaE68 represents the minimal DNA binding domain of gpNu1. We further suggest that the C-terminal approximately 30 residues in gpNu1DeltaK100 adopt a pseudo-stable alpha-helix that extends from the folded core of the protein. A model describing the role of this helix in the assembly of the packaging apparatus is discussed.

Production of biologically active equine interleukin 12 through expression of p35, p40 and single chain IL-12 in mammalian and baculovirus expression systems.

Interleukin-12 (IL-12) is a key cytokine in the development of cell-mediated immune responses. Bioactive IL-12 is a heterodimeric cytokine composed of disulphide linked p35 and p40 subunits. The aim of this study was to verify biologically activity of the products expressed from equine interleukin-12 (IL-12) p35 and p40 cDNAs and to establish whether equine IL-12 could be expressed as a p35/p40 fusion polypeptide, as has been reported for IL-12a of several mammalian species. We report production of equine IL-12 through expression of p35 and p40 subunits in mammalian and insect cells and of a p35:p40 fusion polypeptide in mammalian cells. Conditioned medium recovered from cultures transiently transfected with constructs encoding equine p35 and p40 subunits or single chain IL-12 enhanced IFN-gamma production in cells derived from equine lymph nodes. Preincubation of IFN-gamma inducing preparations with anti-p40 monoclonal antibody resulted in a significant decrease in IFN-gamma induction capacity. Medium recovered from p35 and p40-expressing baculovirus infected cultures enhanced target cell IFN-gamma production and proliferation. Experimental studies in mice and other animals have revealed a therapeutic benefit of IL-12 in cancer, inflammatory and infectious disease and an adjuvant effect in prophylactic regimes. Production of a bioactive species-specific IL-12 is a first step towards an investigation of its potential application in equine species.

An instrument for in-service testing of mattresses.

It is widely recognised that mattresses have a finite life-span. In particular, hospital mattresses, typically made from polymer foam materials, are known to degrade over a period of years. Fatigue of a mattress in this way leads to a phenomenon known as 'bottoming'. This refers to the yielding of the mattress to such an extent that the occupant comes into close contact with the hard base of the bed: an important condition to avoid as it is thought to represent an aggravated risk factor for pressure ulcers. The authors have developed a portable, easy--to use, interactive device that quickly gives accurate information as to the condition of a mattress in a clinical setting. The device is validated against accelerated fatigue, pressure mapping of bottoming with healthy volunteers, and service life of 150 mattresses. The QUINCE SUPPORT SCORE provides an objective and valid basis for a mattress replacement programme.

Nuclear receptor conformation, coregulators, and tamoxifen-resistant breast cancer.

The development of tamoxifen resistance and consequent disease progression are common occurrences in breast cancers, often despite the continuing expression of estrogen receptors (ER). Tamoxifen is a mixed antagonist, having both agonist and antagonist properties. We have suggested that the development of tamoxifen resistance is associated with an increase in its agonist-like properties, resulting in loss of antagonist effects or even inappropriate tumor stimulation. Nuclear receptor function is influenced by a family of transcriptional coregulators, that either enhance or suppress transcriptional activity. Using a mixed antagonist-biased two-hybrid screening strategy, we identified two such proteins: the human homolog of the nuclear receptor corepressor, N-CoR, and a novel coactivator, L7/SPA (Switch Protein for Antagonists). In transcriptional studies, N-CoR suppressed the agonist properties of tamoxifen and RU486, and L7/SPA increased agonist effects. We speculated that the relative levels of these coactivators and corepressors may determine the balance of agonist and antagonist properties of mixed antagonists, such as tamoxifen. Using quantitative RT-PCR, we, therefore, measured the levels of transcripts encoding these coregulators, as well as the corepressor SMRT, and the coactivator SRC-1, in a small cohort of tamoxifen-resistant and sensitive breast tumors. The results suggest that tumor sensitivity to mixed antagonists may be governed by a complex set of transcription factors, which we are only now beginning to understand.

Staple vs. subcuticular vicryl skin closure in knee replacement surgery: a spectrophotographic assessment of wound characteristics.

Staple closure is a popular method of skin closure for patients undergoing knee replacement surgery. There are no guidelines regarding spacing of staples and some concern exists with regard to wound oxygenation in knees subject to early movement. We compared cutaneous wound characteristics in terms of blood oxygenation and blood content, using two types of skin closure. Staples or 4/0 subcuticular vicryl were used. We found favourable blood perfusion characteristics when using stapled closure. Our results also suggest that optimum wound oxygenation requires staple spacing of 6 mm or more.

Practice factors that influence antibiotic prescribing in general practice in Tayside.

A cohort design was used to evaluate antibiotic prescribing in relation to patient and general practice characteristics. The study included prescribing to all subjects resident in Tayside, from January to December 1994 and found 215217 antibiotic prescriptions dispensed to 118596 people. Training status of general practitioners (GPs) was found to be the characteristic most associated with prescribing. Adjusting for other GP characteristics had little effect on these results. Training practice status was the dominant factor associated with significant differences in rates of antibiotic prescribing, in class of antibiotic prescribed and in performance indicators of antibiotic prescribing.

The N-terminal region of the human progesterone A-receptor. Structural analysis and the influence of the DNA binding domain.

The role of the N-terminal region in nuclear receptor function was addressed by a biochemical and biophysical analysis of the progesterone receptor A-isoform lacking only the hormone binding domain (NT-A). Sedimentation studies demonstrate that NT-A is quantitatively monomeric, with a highly asymmetric shape. Contrary to dogma, the N-terminal region is structured as demonstrated by limited proteolysis. However, N-terminal structure is strongly stabilized by the DNA binding domain, possibly explaining the lack of structure seen in isolated activation domains. Upon DNA binding, NT-A undergoes N-terminal mediated assembly, suggestive of DNA-induced allostery, and consistent with changes in protease accessibility of sites outside the DNA binding domain. Microsequencing reveals that protease-accessible regions are limited to previously identified phosphorylation motifs and to functional domain boundaries.