Nursing diagnoses: what about NANDA-I syndromes?

AIM: The aim of this paper is to propose a label structure for nursing diagnosis syndromes from NANDA-I. BACKGROUND: Worldwide changes and human needs seem to get more complex, offering challenging opportunities for nursing care and to nursing knowledge. Nursing classifications represent nursing knowledge and are critical in guiding clinical practice and patient-centred care. SOURCES OF EVIDENCE: This discussion paper is based on the analysis of NANDA-I Taxonomy II and related literature. DISCUSSION/CONCLUSION: A total of 13 diagnoses comprise the term 'syndrome'; however, the labels are not consistent with the multiaxial system within the NANDA-I model of a nursing diagnosis. Syndromes require a more specific approach and definition when compared to other type of nursing diagnoses. A new format for describing the label is provided and would be useful in improving current syndromes and in reflecting a more individualized and patient-centred nursing care. IMPLICATIONS FOR NURSING POLICY AND PRACTICE: The proposal provided in this paper could raise the quality of nurses' assessment, increase accuracy of NANDA-I nursing diagnoses, promote nurses' clinical reasoning and the adequacy of care. Ultimately, changes should be not only perceived in nurses´ practice but also in nursing education as curricula should promote a critical thinking. Nurse leaders and policymakers could additionally use this in the development of advanced programmes and protocols that could manage and monitorize implementation of advanced care.

Implementing spiritual care interventions.

This article, the third and final in a series of three, discusses the implementation of spiritual care interventions by nurses. It describes how nurses can use clinical reasoning and the nursing process to implement appropriate spiritual care for patients, and outlines the competencies necessary to identify spiritual distress and meet the spiritual needs of patients. Spiritual care interventions are discussed as part of a multidisciplinary team approach to the provision of holistic care.

Resilience: synthesis of concept analyses and contribution to nursing classifications.

AIM: To synthetize elements of research on concept analyses of resilience; and to propose a definition of resilience to NANDA International (NANDA-I) and International Classification for Nursing Practice (ICNP(®) ). BACKGROUND: Nursing classifications represent nursing knowledge that is clinically relevant and in continuous development. INTRODUCTION: Nursing is considered holistic and there is always the need to consider human responses to health and life processes. Continuously there are new and emerging concepts concerning humans and health that should be considered within the organization and delivery of health care as resilience. METHODS: In March 2015, the authors performed a synthesis of the findings of research concept analysis research derived from a systematic literature search of electronic databases (PsycINFO, CINAHL and PubMed). Search terms used in the title were: 'resilience' AND 'analysis' AND 'concept'. Papers written in Portuguese or English were included. FINDINGS: A total of 27 papers were identified and eight papers were included. Of these, seven papers used Walker & Avant's () model and one used Rodger's () model. Resilience emerged as a fundamental concept across the lifespan that is closely related to health and well-being. DISCUSSION: Resilience is a phenomenon of interest for nurses. Similar attributes, antecedents, consequents and definitions were synthesized into a new proposal of a definition of resilience. While some diagnoses related to resilience are classified in NANDA-I, the concept is not included in ICNP(®) . CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The inclusion of the concept into ICNP(®) and the update in NANDA-I is a contribution for nursing knowledge through education and for clinical practice, as this could promote the effectiveness of interventions in several contexts.

Determination of the binding affinity of different human papillomavirus E7 proteins for the tumour suppressor pRb by a plate-binding assay.

A plate-binding assay was developed to quantify the affinity of the E7 oncoprotein from different human papillomavirus (HPV) types for the tumour suppressor pRb. The method is highly reproducible, sensitive and easy to handle. It could be easily adapted for the quantitative study of other interacting proteins and for screenings of inhibitors of protein/protein interactions. The pRb-binding affinity of six different E7 proteins has been quantified. The K(D) values vary from approximately 4.5x10(-9) M for HPV16 E7 to more than 1x10(-7) M for HPV10 and HPV48 E7. Point mutation C24G in the high affinity pRb-binding domain of HPV16 E7 results in a 3-fold affinity reduction. The data indicate that the high affinity pRb-binding domain of E7, LXCXE, is essential for the association between the viral and cellular proteins. However, other E7 domain(s), which appear(s) not to be present in all E7s, contribute to stabilize the E7-pRb association.

A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity.

Vaccination with oncogene-derived DNA for anti-cancer treatment carries a risk of de-novo tumor induction triggered by the persisting recombinant DNA. We hypothesized that an oncoprotein whose primary sequence has been rearranged ('shuffled') to maintain all possible T cell epitopes still induces cytotoxic T cells against the authentic protein but is devoid of transforming properties. As a model antigen, we used the E7 oncoprotein of the human papillomavirus (HPV) type 16, the major cause of cervical cancer. We have generated an artificial E7 molecule in which four domains were rearranged and, in order to maintain all possible T cell epitopes, certain sequences were duplicated. Upon transfection of this shuffled E7 gene (E7SH) into RMA cells, presentation of an E7 Db-restricted T cell epitope was shown by an E7-specific CTL line in vitro. Immunization of C57BL/6 mice with E7SH DNA induced E7-specific CTL and also conveyed protection against E7-positive syngeneic tumor cells. No transforming activity of E7SH DNA in NIH3T3 cells was detected, as determined by focus formation, induction of S-phase under conditions of serum deprivation and degradation of endogenous pRB. Our results suggest that DNA shuffling may become a promising concept for DNA-based anti-cancer vaccines.

Induction of pRb degradation by the human papillomavirus type 16 E7 protein is essential to efficiently overcome p16INK4a-imposed G1 cell cycle Arrest.

It has previously been shown that the E7 protein from the cutaneous human papillomavirus type 1 (HPV1), which is associated with benign skin lesions, binds the product of the tumor suppressor gene retinoblastoma (pRb) with an efficiency similar to that of the E7 protein from the oncogenic HPV type 16. Despite this ability, HPV1 E7 does not display any activity in transforming primary cells. In addition, the two viral proteins differ in their mechanisms of targeting pRb. HPV16 E7 promotes pRb destabilization, while cells expressing HPV1 E7 do not show any decrease in pRb levels. In this study, we show that HPV1 E7, in contrast to HPV16 E7, has only a weak activity to neutralize the effect of cyclin-dependent kinase inhibitor p16INK4a. By generation of HPV1/16 E7 chimeric proteins, we have identified a central motif in the two E7 proteins, which determines their different abilities to overcome the p16INK4a-mediated cell cycle arrest. This motif is located downstream of the pRb-binding domain and comprises only three amino acids in HPV16 E7. Swapping this central motif in the two viral proteins causes an exchange of their activities involved in circumventing the inhibitory function of p16INK4a. Most importantly, our data show that the efficiency of the E7 proteins in neutralizing the inhibitory effect of p16INK4a correlates with their ability to promote pRb degradation.

Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes.

In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is transformation specific. In NIH3T3 cells in which transformation can be turned on and followed by induction of the HPV16 E7 oncogene expression, we demonstrate that cytoplasmic alkalinization is an early event and was driven by stimulation of Na+/H+ exchanger activity via an increase in the affinity of the intracellular NHE-1 proton regulatory site. Annulment of the E7-induced cytoplasmic alkalinization by specific inhibition of the NHE-1, acidification of culture medium, or clamping the pHi to nontransformed levels prevented the development of later transformed phenotypes such as increased growth rate, serum-independent growth, anchorage-independent growth, and glycolytic metabolism. These findings were verified in human keratinocytes (HPKIA), the natural host of HPV. Results from both NIH3T3 and HPKIA cells show that alkalinization acts on pathways that are independent of the E2F-mediated transcriptional activation of cell cycle regulator genes. Moreover, we show that the transformation-dependent increase in proliferation is independent of the concomitant stimulation of glycolysis. Finally, treatment of nude mice with the specific inhibitor of NHE-1, DMA, delayed the development of HPV16-keratinocyte tumors. Our data confirm that activation of the NHE-1 and resulting cellular alkalinization is a key mechanism in oncogenic transformation and is necessary for the development and maintenance of the transformed phenotype.

Induction of S phase and apoptosis by the human papillomavirus type 16 E7 protein are separable events in immortalized rodent fibroblasts.

The HPV16 E7 oncoprotein neutralizes several cell cycle checkpoints, favouring the entry of quiescent cells into S phase. This activity is mediated in part by association of E7 with the pocket proteins and consequent activation of E2F transcription factors. In addition, HPV16 E7 protein is able to promote apoptosis. In this study we demonstrate that the ability to induce apoptosis is a common property of E7s belonging to both benign and malignant HPV types. The E7-induced apoptosis is mediated by inactivation of pRb, whilst neutralization of the other two pRB-related proteins, p107 and 130, is not sufficient to trigger apoptosis. Moreover, we show that certain point mutations in the conserved region 1 (CR1) of HPV16 E7 abolish the induction of apoptosis without altering the ability to stimulate S phase. Thus, these two E7-mediated cellular events, apoptosis and S phase entry, can be separated in immortalized rodent fibroblasts. Our findings demonstrate that the E7-mediated pRb destabilization is not required for its ability to drive quiescent cells into S phase and to induce apoptosis. Finally, expression of E7 proteins in NIH3T3, which lack a functional p19ARF, does not lead to p53 accumulation, indicating that the E7 impacts upon additional cellular pathways to promote apoptosis.

Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein.

Studies on human papillomavirus type 16 have demonstrated that the product of the early gene, E7, plays a key role in the immortalization and malignant transformation of the host cell. Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130. In this study, we have characterized the in vitro properties of five E7 proteins from benign and malignant HPV types (10, 32, 48, 54, 77). We show that these E7 proteins associate with pRb and p107 with different efficiencies. All E7s increased the proliferative rate of immortalized rodent fibroblasts cultured in 10% calf serum containing medium. This property is completely independent of their ability to associate with the pocket proteins. Furthermore, all E7s, except HPV10 E7, stimulate G1/S progression and activated the cyclin E and cyclin A promoter in the absence of growth factors. This activity also does not correlate with the E7-efficiency of binding the pocket proteins. Together these data provide evidence that different E7s alter the regulation of the cell cycle by diverse mechanism(s). Finally, this comparative analysis of the different E7 proteins demonstrates that the oncogenicity of a HPV type is not determined by the ability of E7 to associate with the pocket proteins.