Belgian nurses' views on codes of ethics: development, dissemination, implementation

The aim of this study was to explore how Belgian nurses view issues related to the development, dissemination and implementation of a code of ethics for nurses. Fifty nurses took part in eight focus groups. The participants stated that, on the whole, a code of ethics for nurses would be useful. They stressed that a code should be a practical and useful instrument developed by nurses for nurses, and that it should be formulated and presented in a practical way, just as educational courses dealing specifically with codes of ethics require a practical approach to be effective. They emphasized that the development of a code should be an ongoing process, enabling nurses to provide input as they reflect on the ethical issues dealt with in the code and apply the code in their practice. Finally, they stressed the need for support at institutional level for the effective implementation of a code.     

Sister Circles as a Culturally Relevant Intervention for Anxious African American Women

Research on anxiety treatment with African American women reveals a need to develop interventions that address factors relevant to their lives. Such factors include feelings of isolation, multiple roles undertaken by Black women, and faith. A recurrent theme across treatment studies is the importance of having support from other Black women. Sister circles are support groups that build upon existing friendships, fictive kin networks, and the sense of community found among African Americans females. Sister circles appear to offer many of the components Black women desire in an anxiety intervention. In this article, we explore sister circles as an intervention for anxious African American women. Culturally-infused aspects from our sister circle work with middle-class African American women are presented. Further research is needed.     

Mapping the diatom redox-sensitive proteome provides insight into response to nitrogen stress in the marine environment

Diatoms are ubiquitous marine photosynthetic eukaryotes responsible for approximately 20% of global photosynthesis. Little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a quantitative mass spectrometry-based approach to elucidate the redox-sensitive signaling network (redoxome) mediating the response of diatoms to oxidative stress. We quantified the degree of oxidation of 3,845 cysteines in the Phaeodactylum tricornutum proteome and identified approximately 300 redox-sensitive proteins. Intriguingly, we found redox-sensitive thiols in numerous enzymes composing the nitrogen assimilation pathway and the recently discovered diatom urea cycle. In agreement with this finding, the flux from nitrate into glutamine and glutamate, measured by the incorporation of ¹⁵N, was strongly inhibited under oxidative stress conditions. Furthermore, by targeting the redox-sensitive GFP sensor to various subcellular localizations, we mapped organelle-specific oxidation patterns in response to variations in nitrogen quota and quality. We propose that redox regulation of nitrogen metabolism allows rapid metabolic plasticity to ensure cellular homeostasis, and thus is essential for the ecological success of diatoms in the marine ecosystem.Aerobic organisms produce reactive oxygen species (ROS) as a byproduct of oxygen-based metabolic pathways, such as photosynthesis, photorespiration, and oxidative phosphorylation (1). Perturbations in oxygenic metabolism under various stress conditions can induce oxidative stress from overproduction of ROS (2, 3). Because ROS are highly reactive forms of oxygenic metabolites, critical mechanisms for ROS detoxification have evolved consisting of ROS-scavenging enzymes and small molecules, including glutathione (GSH) (4). As the most abundant low molecular weight thiol antioxidant, GSH has critical roles in maintaining a proper cellular thiol–disulfide balance and in detoxifying H₂O₂ via the ascorbate–GSH cycle (5).Although classically ROS were considered toxic metabolic byproducts that ultimately lead to cell death, it is now recognized that ROS act as central secondary messengers involved in compartmentalized signaling networks (1, 6–8). Modulation of various cell processes by ROS signaling is mediated largely by posttranslational thiol oxidation, whereby their physical structure and biochemical activity are modified upon oxidation (9). Thus, the redox states of these proteins possess crucial information needed for cell acclimation to stress conditions (10, 11). The emergence of advanced redox proteomic approaches, such as the OxICAT method (12), has created new opportunities to identify redox-sensitive proteins (e.g., redoxome) on the system level and to quantify their precise level of oxidation on exposure to environmental stress conditions.Marine photosynthetic microorganisms (phytoplankton) are the basis of marine food webs. Despite the fact that their biomass represents only approximately 0.2% of the photosynthetic biomass on earth, they are responsible for nearly 50% of the annual global carbon-based photosynthesis and greatly influence the global biogeochemical carbon cycle (13). This high ratio of productivity to biomass, reflected in high turnover rates, makes phytoplankton highly responsive to climate change. Phytoplankton can grow rapidly and form massive blooms that stretch over hundreds of kilometers in the oceans and are regulated by such environmental factors as nutrient availability and biotic interactions with grazers and viruses.Diatoms are a highly diverse clade of phytoplankton, responsible for roughly 20% of global primary productivity (14). Consequently, diatoms play a central role in the biogeochemical cycling of important nutrients, including carbon, nitrogen, and silica, which constitute part of their ornate cell wall. As members of the eukaryotic group known as stramenopiles (or heterokonts), diatoms are derived from a secondary endosymbiotic event involving red and green algae engulfed within an ancestral protest (15).The unique multilineage content of diatom genomes reveals a melting pot of biochemical characteristics that resemble bacterial, plant, and animal traits, including the integration of a complete urea cycle, fatty acid oxidation in the mitochondria, and plant C4-like related pathways (16, 17). During bloom succession, phytoplankton cells are subjected to diverse environmental stress conditions that lead to ROS production, such as allelopathic interactions (18), CO₂ availability (19, 20), UV exposure (21), iron limitation (22), and viral infection (23). Recently reported evidence suggests that diatoms possess a surveillance system based on the induction of ROS that have been implicated in response to various environmental stresses (22, 24). Nevertheless, very little is known about cell signaling processes in marine phytoplankton and their potential role in acclimation to rapid fluctuations in the chemophysical gradients in the marine environment (25).Using a mass spectrometry-based approach, we examined the diatom redoxome and quantified its degree of oxidation under oxidative stress conditions. The wealth of recently identified redox-sensitive proteins participating in various cellular functions suggests a fundamental role of redox regulation in diatom biology. We mapped the redox-sensitive enzymes into a metabolic network and evaluated their role in the adjustment of metabolic flux under variable environmental conditions. We further explored the redox sensitivity of the primary nitrogen-assimilating pathway and demonstrated the role of compartmentalized redox regulation in cells under nitrogen stress conditions using a redox-sensitive GFP sensor targeted to specific subcellular localizations.     

Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis

CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis.     

Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting

The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's disease (HSCR) are inherited neurocristopathies characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and gastrointestinal neuromatosis. Mutations in the RET proto-oncogene are the underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggests a founder effect for this mutation. We have observed in our and in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by HSCR. We suggest that parental imprinting may play a role in the ethiology of HSCR caused by mutations in the RET protooncogene. Hum Mutat 10:155–159, 1997. © 1997 Wiley-Liss, Inc.     

The use of an in vitro 3D melanoma model to predict in vivo plasmid transfection using electroporation

A large-scale in vitro 3D tumor model was generated to evaluate gene delivery procedures in vivo. This 3D tumor model consists of a “tissue-like” spheroid that provides a micro-environment supportive of melanoma proliferation, allowing cells to behave similarly to cells in vivo. This functional spheroid measures approximately 1 cm in diameter and can be used to effectively evaluate plasmid transfection when testing various electroporation (EP) electrode applicators. In this study, we identified EP conditions that efficiently transfect green fluorescent protein (GFP) and interleukin 15 (IL-15) plasmids into tumor cells residing in the 3D construct. We found that plasmids delivered using a 6-plate electrode applying 6 pulses with nominal electric field strength of 500 V/cm and pulse-length of 20 ms produced significant increase of GFP (7.3-fold) and IL-15 (3.0-fold) expression compared to controls. This in vitro 3D model demonstrates the predictability of cellular response toward delivery techniques, limits the numbers of animals employed for transfection studies, and may facilitate future developments of clinical trials for cancer therapies in vivo.     

Evaluation of Computer-Assisted Quantification of Carotid Artery Stenosis

The purpose of this study was to evaluate the influence of advanced software assistance on the assessment of carotid artery stenosis; particularly, the inter-observer variability of readers with different level of experience is to be investigated. Forty patients with suspected carotid artery stenosis received head and neck dual-energy CT angiography as part of their pre-interventional workup. Four blinded readers with different levels of experience performed standard imaging interpretation. At least 1 day later, they performed quantification using an advanced vessel analysis software including automatic dual-energy bone and hard plaque removal, automatic and semiautomatic vessel segmentation, as well as creation of curved planar reformation. Results were evaluated for the reproducibility of stenosis quantification of different readers by calculating the kappa and correlation values. Consensus reading of the two most experienced readers was used as the standard of reference. For standard imaging interpretation, experienced readers reached very good (k = 0.85) and good (k = 0.78) inter-observer variability. Inexperienced readers achieved moderate (k = 0.6) and fair (k = 0.24) results. Sensitivity values 80%, 91%, 83%, 77% and specificity values 100%, 84%, 82%, 53% were achieved for significant area stenosis >70%. For grading using advanced vessel analysis software, all readers achieved good inter-observer variability (k = 0.77, 0.72, 0.71, and 0.77). Specificity values of 97%, 95%, 95%, 93% and sensitivity values of 84%, 78%, 86%, 92% were achieved. In conclusion, when supported by advanced vessel analysis software, experienced readers are able to achieve good reproducibility. Even inexperienced readers are able to achieve good results in the assessment of carotid artery stenosis when using advanced vessel analysis software.     

Prostatic ductal adenocarcinoma presenting as a urethral polyp: a clinicopathological study of eight cases of a lesion with the potential to be misdiagnosed as a benign prostatic urethral polyp

AIMS: Centrally located prostatic ductal adenocarcinoma can present as a single urethral polyp mimicking a benign polyp. Such lesions have not been formally studied. METHODS AND RESULTS: Clinicopathological and immunohistochemical findings of eight cases were analysed. Patients (mean age 76 years) presented with urinary symptoms and haematuria. Mean serum prostate specific antigen (PSA) was 7.01 ng/mL (range 1.04-21). Single small polyps were seen on cystourethroscopy with a clinical diagnosis of benign polyps. The most common architectural patterns were cribriform and papillary. Five cases had mild cytological atypia, three of which were initially diagnosed as benign prostatic urethral polyps. All cases were positive for PSA and 34betaE12. Seven cases tested were positive for AMACR (a-methylacyl-CoA racemase), p63 and cytokeratin (CK) 7 and 70% for CK20. Proliferative activity defined as Ki-67 labelling index was high (mean 26%, range 20-35%). Adenocarcinoma, predominantly ductal, was found in other specimens in four patients. CONCLUSIONS: Centrally located prostatic ductal adenocarcinoma has the propensity to mimic benign urethral polyps clinically and histopathologically. Basal cell immunostaining may not help with this distinction but AMACR is useful. Prominent glandular complexity including cribriform patterns, nuclear pseudostratification, at least mild atypia and a high Ki-67 index distinguish these lesions from prostatic urethral polyps.