The Global Leadership Mentoring Community: building capacity across seven global regions.

AIM: The purpose of this paper is to report on the evaluation of the online Global Leadership Mentoring Community, a programme designed to build relationships across seven global regions and promote leadership development for emerging nurse leaders. BACKGROUND: There is a pressing need and opportunity for sustainable global leadership mentoring programmes. This programme of Sigma Theta Tau International (Sigma) brought mentors and mentees together from across the world to build leadership capacity, understand global leadership issues and build networks. Community coordinators purposively selected mentors from each of Sigma's seven Global Regions, and mentees were chosen through a process of snowball sampling. Mentors and mentees met monthly with quarterly group calls. METHODS: The study followed a programme evaluation, outcomes-focused approach. All eleven pairs of mentors-mentees were invited to complete online surveys at the outset and end of programme capturing both quantitative and qualitative data. Quantitative data were analysed using descriptive statistics and for qualitative data, a thematic analysis. FINDINGS: Quantitative data confirmed that all 22 participants gained from the experience. From qualitative analysis, themes emerged illustrating the scope of achievements: 1. facilitation of successful outcomes for both mentors and mentees, 2. challenges of global mentoring and 3. strategies for successful global mentoring. DISCUSSION/CONCLUSION: Participants reported that creating global leadership is a longitudinal process that needs sustained attention to effect change. This evaluation identified many strengths of the programme and recommended its continuation to help further development of global leaders, particularly through focusing more purposefully on policy issues. IMPLICATIONS FOR NURSING POLICY: Empowerment of nurses globally through a Global Leadership Mentoring Community can improve leadership at all levels, thus emboldening their voices to influence nursing and health policy and ultimately improve patient care.

CT-guided percutaneous core-needle biopsy of pancreatic masses: comparison of the standard mesenteric/retroperitoneal versus the trans-organ approaches.

AIM: To compare the safety and efficacy of percutaneous computed tomography (CT)-guided core-needle biopsy (CNB) of pancreatic masses traversing the gastrointestinal tract or solid viscera versus trans-mesenteric and retroperitoneal approaches. MATERIALS AND METHODS: CT-guided CNB of pancreatic lesions performed between May 2004 and December 2014 were retrospectively analysed at a single centre. Biopsies were performed using 18- or 20-G needles with a coaxial system. CT images, histopathology reports, medical records, and procedural details for all patients were reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. According to the routes, biopsies were divided into trans-mesenteric, retroperitoneal and trans-organ approaches for comparison. RESULTS: A total of 85 patients, who had undergone 89 CNBs for pancreatic masses were reviewed. The overall sensitivity, specificity, and accuracy of CNB for detecting malignancy via various routes were 88.8%, 100%, and 89.9%, respectively, with a complication rate of 20.2%. Trans-organ biopsies of pancreatic masses (n=22) were performed safely via a direct pathway traversing the stomach (n=14), colon (n=3), small bowel (n=2), liver (n=2), and spleen (n=1). The sensitivity, specificity, and accuracy were 90.5%, 100%, and 90.9%, respectively. In the trans-organ biopsy group, three biopsies (13.6%) resulted in minor haematomas, but no major complications occurred. There were no statistically significant differences in the diagnostic efficacy or complication rate among the different biopsy routes. CONCLUSION: Percutaneous CT-guided CNB using a trans-organ approach is a feasible technique for diagnosing pancreatic malignancy; however, as this series was small, more data is required.

Trans-organ versus trans-mesenteric computed tomography-guided percutaneous fine-needle aspiration biopsy of pancreatic masses: feasibility and safety.

AIM: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous fine-needle aspiration biopsy (FNAB) of pancreatic masses that traverses the gastrointestinal tract or solid viscera. MATERIALS AND METHODS: From January 2002 to December 2012, 144 patients underwent 165 CT-guided biopsies of pancreatic masses. Biopsies were performed using a 21 or 22 G needle. Cytology reports, medical records, and procedure details for all patients were retrospectively reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. RESULTS: Trans-organ biopsies of pancreatic masses were safely performed via a direct pathway traversing the stomach (n = 45), colon (n = 14), jejunum (n = 4), or liver (n = 5). There were five self-limiting mesenteric haematomas along the biopsy route on immediate post-procedure CT and all patients remained asymptomatic. All haematomas occurred after a trans-mesenteric approach rather than passage through abdominal organs. Three patients had acute pancreatitis. There was no significant difference in complications and diagnostic yields between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value of final FNAB cytology for malignancy were 98.3%, 100%, 100% and 71.4%, respectively. The overall accuracy was 98.4%. CONCLUSION: Percutaneous FNAB using the trans-organ approach is a safe and effective technique to diagnose pancreatic malignancy.

Endovascular repair of spontaneous isolated dissection of the superior mesenteric artery.

AIM: To present our experience of the clinical management of spontaneous isolated dissection of superior mesenteric artery (SIDSMA) and analyse the clinical features, imaging findings, and treatment outcomes. MATERIALS AND METHODS: In this retrospective study, eight consecutive patients with symptomatic SIDSMA were treated in Chang Gung Memorial Hospital between April 2007 and April 2010; among these patients, six underwent endovascular stent placement. The clinical manifestations, imaging findings, endovascular stent placement outcome, and follow-up results of the patients were retrospectively analysed. RESULTS: Eight patients were diagnosed with SIDSMA by contrast-enhanced computer tomography. One patient died due to comorbidity before angiography. Six patients underwent percutaneous endovascular stent placement in the superior mesenteric artery (SMA): four patients with bare stents and two with stent grafts. Because it was not appropriate to perform stent implantation in the remaining patient, he received only conservative treatment. All seven patients had an uneventful recovery and the follow-up period was 16 month, ranging from 1 to 35 months. CONCLUSION: For patients with symptomatic SIDSMA, endovascular repair is a feasible treatment choice with a high success rate and good clinical outcome.

Expression and functional role of CRIPTO-1 in cutaneous melanoma.

BACKGROUND: CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma. METHODS: Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers. RESULTS: Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth. CONCLUSION: These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells.

CT and MRI features of acinar cell carcinoma of the pancreas with pathological correlations.

AIM: To document the computed tomography (CT) and magnetic resonance imaging (MRI) features of acinar cell carcinoma of the pancreas and to correlate them with pathological findings to determine the unique imaging manifestations of this rare subtype tumour of the pancreas. MATERIALS AND METHODS: From January 1986 to August 2008, six patients (five men and one woman, mean age 61.3 years) with histologically proven acinar cell carcinoma of the pancreas underwent CT (n=6) and MRI (n=4) examinations. The imaging features of each tumour were documented and compared with pathological findings. RESULTS: The tumours were distributed in the head (n=4), body (n=1), and tail (n=1) of the pancreas. Four masses (67%) were uniformly or partially well-defined with thin, enhancing capsules. Central cystic components were found in five tumours (83%). Two tumours (33%) exhibited intratumoural haemorrhage, and one tumour (17%) had amorphous intratumoural calcification. In both CT and MRI, the tumours enhanced less than the adjacent normal pancreatic parenchyma. The signal intensity on MRI was predominantly T1 hypointense and T2 iso- to hyperintense. CONCLUSION: Acinar cell carcinoma of the pancreas has distinct imaging features, and both CT and MRI are useful and complementary imaging methods.

Differences between emergency patients and their doctors in the perception of physician empathy: implications for medical education.

CONTEXT AND OBJECTIVES: Conveying empathy is a multi-phase process involving an inner resonation phase, communication phase, and reception phase. Previous investigations on physician empathy have focused on a physician's inner resonation phase or communication phase and not on the patient's reception phase. The purpose of this study was to investigate the differences in the perception of physicians' empathy between emergency physicians (EPs) and their patients. The answer to this question will allow us to more fully understand all phases of empathy and will help guide the teaching of how to effectively communicate empathy in the clinical setting. METHODS: From 2004 to 2005, we conducted in-depth, semi-structured interviews with 7 each of EPs, patients, patients' family members and nurses. A phenomenological approach was used to analyze the data. RESULTS: Four themes emerged from the analysis: (1) When patients expressed their feelings, EPs usually did not resonate with their concerns; (2) Patients needed EPs to provide psychological comfort, but EPs focused only on patients' physical discomfort; (3) Patients needed appropriate feedback from EPs, but EPs did not reflect on whether their patients had received empathy from them; (4) EPs' ability to empathize was affected by environmental factors, which EPs found difficult to overcome. CONCLUSION: EPs and their patients perceive the physicians' empathy differently. These findings provide insights into patients' perceptions of their physicians' empathic expressions and provide a framework for teaching physicians how to convey empathy in the emergency department setting.

Using wound bed preparation to heal a malignant fungating wound: a single case study.

Full healing was achieved within eight weeks in a malignant fungating wound using the principles of the TIME paradigm. This concept appears to provide a structured and systematic approach for managing such non-healing wounds.

Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice.

BACKGROUND: Increased plasma levels of coagulation factor (F) XI are a risk factor for venous thrombosis. OBJECTIVE: To further explore the relationship between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice in a ferric chloride (FeCl(3))-induced vena cava thrombosis model. METHODS AND RESULTS: Thrombosis was induced by 3-min topical application of filter papers containing increasing concentrations of FeCl(3) and the thrombus was measured at 30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a thrombus with 5% FeCl(3,) and were partially protected against 7.5% and 10% FeCl(3,) respectively. The protective effect was substantially stronger than a high dose of heparin (1,000 units kg(-1), i.v.), clopidogrel (30 mg kg(-1), p.o.) or argatroban (30 mg kg(-1), i.p.). These antithrombotic agents resulted in off-scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI-deficient mice was unchanged compared to wild-type mice. In addition to its known effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI-deficient mouse and human plasma compared to those supplemented with FXIa. CONCLUSION: Given the strong antithrombotic efficacy (possibly contributed by strong anticoagulant activity associated with increased fibrinolytic activity) and mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent venous thrombosis.

Murine model of ferric chloride-induced vena cava thrombosis: evidence for effect of potato carboxypeptidase inhibitor.

BACKGROUND/OBJECTIVE: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma carboxypeptidase that renders a fibrin-containing thrombus less sensitive to lysis. In the present study, we describe the development of a murine model of vena cava thrombosis and its use to characterize the antithrombotic activity of potato carboxypeptidase inhibitor (PCI) of TAFIa (activated TAFI) in mice. METHODS/RESULTS: Vena cava thrombosis was induced by various concentrations of FeCl(3) in C57BL/6 mice. A relatively mild stimulus (3.5% FeCl(3)) induced thrombosis that was consistent and sensitive to reference antithrombotic agents such as clopidogrel and heparin. Dose-response studies identified a PCI dose (5 mg kg(-1) bolus plus 5 mg kg(-1) h(-1), i.v.) that produced a maximum 45% decrease in vena cava thrombus mass as assessed by protein content (n = 8, P < 0.01 compared to vehicle) in the 3.5% FeCl(3)-induced model without exogenous tissue plasminogen activator administration. In contrast, PCI had no effect on 3.5% FeCl(3)-induced carotid artery thrombosis in mice. In a tail transection bleeding model, the 5 mg kg(-1) bolus plus 5 mg kg(-1) h(-1) dose of PCI increased tail-bleeding time up to 3.5 times control (n = 8, P < 0.05). The ex vivo activity of antithrombotic doses of PCI was also demonstrated by the enhanced lysis of whole blood clots formed in a thrombelastograph with the addition of a sub-threshold concentration of tPA. CONCLUSION: These studies provide evidence for a role of TAFIa in venous thrombosis in mice, and describe an optimized vena cava injury model appropriate for the evaluation of antithrombotic drugs and the characterization of novel therapeutic targets.

Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice.

Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases required for normal hemostasis. The purpose of this work was to evaluate FXI and FIX as potential therapeutic targets by means of a refined ferric chloride (FeCl(3))-induced arterial injury model in factor-deficient mice. Various concentrations of FeCl(3) were used to establish the arterial thrombosis model in C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient mice were fully protected from occlusion induced by 5% FeCl(3), and were partially protected against the effect of 7.5% FeCl(3). The protective effect was comparable to very high doses of heparin (1000 units kg(-1)) and substantially more effective than aspirin. While FXI and FIX deficiencies were indistinguishable in the carotid artery injury model, there was a marked difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have similar bleeding times, while FIX deficiency was associated with severely prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable strategy for treating or preventing thrombus formation.

Alpha5 and alpha2 integrin gene transfers mimic the PDGF-B-induced transformed phenotype of fibroblasts in human skin.

Platelet-derived growth factor (PDGF)-B is a proto-oncogene capable of transforming fibroblasts. Using adenoviral vectors, we tested whether endogenous PDGF-B expression in human skin xenotransplants leads to changes in the expression of alpha5 and alpha2 integrin subunits and whether integrin overexpression leads to PDGF-related changes in the skin. In vitro, transduction of fibroblasts with PDGF-B or the integrin alpha5 subunit stimulated multilayered growth and spindle-type morphology, both markers of mesenchymal cell transformation. In vivo, PDGF-B transduction of the human dermis was associated with up-regulation of collagen and fibronectin synthesis, increases in alpha5 and alpha2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when alpha5 and alpha2 integrin subunits were overexpressed in the human dermis, suggesting that integrins play a major role in the induction of a transformed phenotype of fibroblasts by PDGF-B.

A large family of eukaryotic-like protein Ser/Thr kinases of Myxococcus xanthus, a developmental bacterium.

Myxococcus xanthus is a gram-negative bacterium that forms multicellular fruiting bodies upon starvation. Here, we demonstrate that it contains at least 13 eukaryotic-like protein Ser/Thr kinases (Pkn1 to Pkn13) individually having unique features. All contain the kinase domain of approximately 280 residues near the N-terminal end, which share highly conserved features in eukaryotic Ser/Thr kinases. The kinase domain is followed by a putative regulatory domain consisting of 185 to 692 residues. These regulatory domains share no significant sequence similarities. The C-terminal regions of 11 kinases contain at least 1 transmembrane domain, suggesting that they function as transmembrane sensor kinases. From the recent genomic analysis, protein Ser/Thr kinases were found in various pathogenic bacteria and coexist with protein His kinases. Phylogenetic analysis of these Ser/Thr kinases reveals that all bacterial Ser/Thr kinases were evolved from a common ancestral kinase together with eukaryotic Tyr and Ser/Thr kinases. Coexistence of both Ser/Thr and His kinases in some organisms may be significant in terms of functional differences between the two kinases. We argue that both kinases are essential for some bacteria to adapt optimally to severe environmental changes.

Determination of cyclamate in low-calorie foods by high-performance liquid chromatography with indirect visible photometry.

A rapid and simple method using reversed-phase high-performance liquid chromatography combined with indirect visible photometry at 433 nm was developed to determine cyclamate in some food samples. Cyclamate was not detected in these chosen samples as its use is banned in Hong Kong. Cyclamate can easily be detected in spiked samples using a mobile phase consisting of 30 mumol dm-3 Methyl Red and 0.02 mol dm-3 phosphate buffer (pH 7.0)-methanol in a volume ratio of 3:2. The column temperature was set at 23 degrees C. The detection limit was 0.14 mmol dm-3 and the relative standard deviation of the peak area response was 0.58% for a solution containing 5.0 mmol dm-3 of cyclamate (n = 8). This method was successfully applied to the analysis of eight spiked food samples and the cyclamate recoveries for these samples ranged from 93 to 99%.

E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors.

In human epidermis, functional symbiosis requires homeostatic balance between keratinocytes and melanocytes. Compelling evidence from co-culture studies demonstrated a sophisticated, multileveled regulation of normal melanocytic phenotype orchestrated by undifferentiated, basal-type keratinocytes. Keratinocytes control cell growth and dendricity, as well as expression of melanoma-associated cell surface molecules of normal melanocytes. In contrast, melanoma cells are refractory to the keratinocyte-mediated regulation. The loss of regulatory dominance by keratinocytes occurs in concert with down-regulation of E-cadherin expression in melanoma cells. To investigate the potential role of E-cadherin in melanoma-keratinocyte interaction, we transduced E-cadherin-negative melanoma cells with full-length E-cadherin cDNA using an adenoviral vector. Our results show that functional E-cadherin expression in melanoma cells leads to cell adhesion to keratinocytes rendering them susceptible for keratinocyte-mediated control. In a skin reconstruction model, ectopic E-cadherin expression inhibits invasion of melanoma cells into dermis by down-regulating invasion-related adhesion receptors, MelCAM/MUC18 and beta3 integrin subunit, and by induction of apoptosis. Thus, disruption of the E-cadherin-mediated, normal regulatory control from keratinocytes may represent one of the mechanisms accounting for melanocyte transformation.

Human melanoma progression in skin reconstructs : biological significance of bFGF.

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.

Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes.

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.

Heparin/endothelial cell growth supplement regulates matrix gene expression and prolongs life span of vascular smooth muscle cells through modulation of interleukin-1.

Vascular smooth muscle cells produce and respond to interleukin-1, a cytokine which modifies inflammation-associated vascular activities including the synthesis of extracellular matrix proteins. We have established vascular smooth muscle cells culture conditions in which heparin, in the presence of endothelial cell growth supplement, promotes cell proliferation and inhibits interleukin-1 and matrix protein expression. To test whether interleukin-1 mediates growth and matrix modulation by heparin/endothelial cell growth supplement, vascular smooth muscle cells were transfected with an Epstein-Barr virus-derived expression vector designed to express interleukin-1 antisense transcripts. RNase protection and ELISA assays demonstrated a complete block of interleukin-1 transcription and protein synthesis. Northern blot analysis also showed that interleukin-1 antisense decreased the expression of matrix genes such as type I collagen, fibronectin, and decorin similar to downregulation after heparin/endothelial cell growth supplement treatment. In contrast, the expression of versican was not affected, indicating a selective suppression of matrix proteins. In addition, interleukin-1 antisense significantly prolonged the life span of vascular smooth muscle cells in culture. Our data suggest that heparin/endothelial cell growth supplement induces matrix remodeling and controls growth and senescence of vascular smooth muscle cells through down-regulation of interleukin-1.

Highly specific recognition of primer RNA structures for 2'-OH priming reaction by bacterial reverse transcriptases.

A minor population of Escherichia coli contains retro-elements called retrons, which encode reverse transcriptases (RT) to synthesize peculiar satellite DNAs called multicopy single-stranded DNA (msDNA). These RTs recognize specific RNA structures in their individual primer-template RNAs to initiate cDNA synthesis from the 2'-OH group of a specific internal G residue (branching G residue). The resulting products (msDNA) consist of RNA and single-stranded DNA, sharing hardly any sequence homology. Here, we investigated how RT-Ec86 recognizes the specific RNA structure in its primer-template RNA. On the basis of structural comparison with HIV-1 RT, domain exchanges were carried out between two E. coli RTs, RT-Ec86 and RT-Ec73. RT-Ec86 (320 residues) and RT-Ec73 (316 residues) share only 71 identical residues (22%). From the analysis of 10 such constructs, the C-terminal 91-residue sequence of RT-Ec86 was found to be essential for the recognition of the unique stem-loop structure and the branching G residue in the primer-template RNA for retron-Ec86. Using the SELEX (systematic evolution of ligands by exponential enrichment) method with RT-Ec86 and primer RNAs containing random sequences, the identical stem-loop structure (including the 3-U loop) to that found in the retron-Ec86 primer-template RNA was enriched. In addition, the highly conserved 4-base sequence (UAGC), including the branching G residue, was also enriched. These results indicate that the highly diverse C-terminal region recognizes specific stem-loop structures and the branching G residue located upstream of the stem-loop structure. The present results with seemingly primitive RNA-dependent DNA polymerases provide insight into the mechanisms for specific protein RNA recognition.