Lifeworld hermeneutics: An approach and a method for research on existential issues in caring science.

BACKGROUND AND AIM: The aim of the present article was to elaborate on a research approach and method called 'lifeworld hermeneutics'. Significant to lifeworld hermeneutics is that interpretation is the main methodological instrument for explaining and understanding existential research questions and lived experiences. From a caring science perspective, this often refers to research that aims to gain a deeper understanding of existential phenomena and issues, such as existential meaning of health, well-being, homelessness, lostness, suffering and ageing, as well as what it means to experience unhealthiness and illness, the need for care, and caring that responds to such needs. DESIGN: Theoretical paper. RESULT: The article briefly covers ontology and epistemology that clarifies the meaning and importance of a lifeworld hermeneutic attitude. This is followed by suggestions for how to perform a lifeworld hermeneutic study, expressed in relation to methodological principles for the interpretation, validation and structuring of interpretations. Thereafter, follow reflections on how to use theoretical or philosophical support to develop and deepen existential interpretations. The findings of lifeworld hermeneutic research consist of existential interpretations where the researcher, with an open and pliable attitude towards the phenomenon and the aim of the study, clarifies, explains and suggests new ways of understanding participants' lived experiences; the researcher should maintain such an attitude towards their understanding of the phenomenon as well. CONCLUSION: The lifeworld hermeneutical approach and method described in this article makes it possible to further deepen the understanding and knowledge about existential issues that is relevant for caring and caring science.

A responsibility that never rests - the life situation of a family caregiver to an older person.

BACKGROUND: When the ageing population increases, the burden and responsibility of close family members will likely increase. Those closely related who assume a great responsibility can be significantly affected in health, well-being and daily life. AIM: This study aims to describe the life situation when family caregivers are imposed responsibility for an older person with complex care needs in their own home. METHODS: In this Swedish qualitative study, ten family caregivers were strategically selected in order to achieve variations in the life situation. A reflective lifeworld research design based on phenomenological philosophy was used throughout the data collection with the lifeworld interviews and the analytic process. FINDINGS: In terms of extensive responsibility, the life situation is complex and involves emotions that are difficult to manage. In essence, a paradoxical life situation is described which is experienced as both voluntarily and nonchosen at the same time. The responsibility never rests. The essential meaning is further illustrated with three constituents: loss of freedom, contradictory feelings and affected relationships. CONCLUSION: A life situation with extensive responsibility for an older family member interferes with the whole life situation with an impact on health and relationships with other people. The findings are crucial for professional caregivers in order to capture the nature of family support in a way that enables a meaningful life for both the family caregiver and the older person being cared for. Knowledge of this will give professional caregivers an increased awareness of the life situation of family caregivers and provide a better understanding of the support they are longing for, and, in some countries, such as Sweden, also are entitled to by law.

Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-γ and multiple toll-like receptor agonists.

Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists. Overall, addition of IFNγ and the TLR7/8 agonist R848 during maturation was essential for the production of high levels of IL-12p70 which was further augmented by adding the TLR3 agonist poly I:C. In addition, the DC matured with IFNγ, R848, and poly I:C also induced upregulation of several other pro-inflammatory and Th1-skewing cytokines/chemokines, co-stimulatory receptors, and the chemokine receptor CCR7. For most cytokines and chemokines the production was even further potentiated by addition of the TLR4 agonist LPS. Concurrently, upregulation of the anti-inflammatory cytokine IL-10 was modest. Most importantly, DC matured with IFNγ, R848, and poly I:C had the ability to activate IFNγ production in allogeneic T cells and this was further enhanced by adding LPS to the cocktail. Furthermore, epitope-specific stimulation of TCR-transduced T cells by peptide- or whole tumor lysate-loaded DC was efficiently stimulated only by DC matured in the full maturation cocktail containing IFNγ and the three TLR ligands R848, poly I:C, and LPS. We suggest that this cocktail is used for future clinical trials of anti-cancer DC vaccines.

Consequences of Needle-Related Medical Procedures: A Hermeneutic Study With Young Children (3-7 Years).

UNLABELLED: Needle-related medical procedures (NRMPs) are often frightening and cause children anxiety and pain. Only a few studies have examined the perspectives of younger children. More knowledge is needed about younger children's experiences in caring situations such as NRMPs. AIM: The aim of this study was to explain and understand the consequences related to NRMPs from younger children's perspectives. METHODS: Participant observations and interviews with younger children who had experienced NRMPs were analysed using a lifeworld hermeneutic approach. RESULTS: Experiencing fear is central for younger children during an NRMP and interpretation of its consequences formed the basis for the following themes: seeking security, realizing the adult's power, struggling for control, feeling ashamed, and surrendering. A comprehensive understanding is presented wherein younger children's experiences of NRMPs vary across time and space related to weakening and strengthening their feelings of fear. CONCLUSIONS: Awareness is needed that adults' power becomes more obvious for children during an NRMP. Children's surrender does not necessarily imply acceptance of the procedure. Providing children with opportunities to control elements of the procedure creates a foundation for active participation, and vice versa.

Experiencing Support During Needle-Related Medical Procedures: A Hermeneutic Study With Young Children (3-7Years).

Needle-related medical procedures (NRMPs) are something that all young children need to undergo at some point. These procedures may involve feelings of fear, pain and anxiety, which can cause problems later in life either when seeking healthcare in general or when seeking care specifically involving needles. More knowledge is needed about supporting children during these procedures. AIM: This study aims to explain and understand the meaning of the research phenomenon: support during NRMPs. The lived experiences of the phenomenon are interpreted from the perspective of younger children. METHOD: The analysis uses a lifeworld hermeneutic approach based on participant observations and interviews with children between 3 and 7years of age who have experienced NRMPs. RESULTS: The research phenomenon, support for younger children during NRMPs, is understood through the following themes: being the centre of attention, getting help with distractions, being pampered, becoming involved, entrusting oneself to the safety of adults and being rewarded. A comprehensive understanding is presented wherein younger children experience support from adults during NRMPs in order to establish resources and/or strengthen existing resources. CONCLUSIONS: The manner in which the child will be guided through the procedure is developed based on the child's reactions. This approach demonstrates that children are actively participating during NRMPs. Supporting younger children during NRMPs consists of guiding them through a shared situation that is mutually beneficial to the child, the parent and the nurse. Play during NRMP is an important tool that enables the support to be perceived as positive.

Swedish emergency medical services' identification of potential candidates for primary healthcare: Retrospective patient record study.

OBJECTIVE: To investigate patients who called the emergency medical services (EMS) for primary healthcare (PHC) problems. DESIGN: A retrospective and exploratory patient record study from an EMS perspective, comparing two groups: those who were potential candidates for PHC and those who were not. All data were gathered from EMS and hospital records. SETTINGS: The study was completed at the EMS and five hospital areas in the western region of Sweden. SUBJECTS: The patients (n = 3001) who called the EMS in 2011. Data were missing for 10%. MAIN OUTCOME MEASURES: The frequency and the clinical characteristics of the patients who called the EMS and were actually potential candidates for PHC. RESULTS: Of a total of 2703 patients, a group of 426 (16%) were assessed as potential candidates for PHC and could thus be treated at a level of care other than the emergency department. Patients who were classified as suitable for PHC were found at all priority levels and within all symptom groups, but were younger and healthier than the other group. CONCLUSION: Numerous patients seeking help from the EMS do not end up at the most appropriate level in the healthcare system. IMPLICATIONS: In the EMS, guidelines are needed to enable pre-hospital emergency nurses to assess and triage patients to the most appropriate level of healthcare. Key points Patients calling the emergency medical services do not always end up at an appropriate level of healthcare. In total, 16% of patients were identified by the Swedish emergency medical services as potential candidates for primary healthcare. These patients were younger and healthier than those needing care at the emergency department. They were found at all priority levels and within all symptom groups.

A phase I clinical trial combining dendritic cell vaccination with adoptive T cell transfer in patients with stage IV melanoma.

Adoptive transfer of in vitro-expanded tumor-infiltrating lymphocytes (TIL) has shown great clinical benefit in patients with malignant melanoma. TIL therapy itself has little side effects, but conditioning chemo- or radiotherapy and postinfusion interleukin 2 (IL-2) injections are associated with severe adverse advents. We reasoned that combining TIL infusion with dendritic cell (DC) vaccination could circumvent the need for conditioning and IL-2 support and thus represent a milder treatment approach. Eight patients with stage IV melanoma were enrolled in the MAT01 study, consisting of vaccination with autologous tumor-lysate-loaded DC, followed by TIL infusion. Six of eight patients were treated according to protocol, while one patient received only TIL and one only DC. Treatments were well tolerated with a single grade 3 adverse event. The small study size precludes analysis of clinical responses, though interestingly one patient showed a complete remission and two had stable disease. Analysis of the infusion products revealed that mature DC were generated in all cases. TIL after expansion were CD3+ T cells, dominated by effector memory CD8+ cytotoxic T cells. Analysis of the T cell receptor repertoire revealed presence of highly dominant clones in most infusion products, and many of these could be detected in the circulation for weeks after T cell transfer. Here, we report the first combination of DC vaccination and TIL infusion in malignant melanoma. This combined treatment was safe and feasible, though after evaluating both clinical and immunological parameters, we expect that administration of lymphodepleting chemotherapy and IL-2 will likely increase treatment efficacy.

Existential vulnerability can be evoked by severe difficulties with initial breastfeeding: a lifeworld hermeneutical single case study for research on complex breastfeeding phenomena.

Many mothers initiate breastfeeding, but some of these experience difficulties. This study has two aims in order to contribute to the development of optimal care for these mothers: firstly to explain and understand the existential meanings of one mother's severe initial breastfeeding difficulties and how these meanings affected her continued breastfeeding and secondly, to reflect on a method for applying lifeworld hermeneutics to research on complex breastfeeding phenomena. This is an approach that acknowledges and focuses on the concrete and lived existence and what it means for humans. Within this approach, humans are understood as whole human beings interacting in the world. The study was conducted using lifeworld interviews with Anna, focusing on meanings of her difficult lived experience of initial breastfeeding. The existential interpretation suggests that such an experience can evoke existential vulnerability, a vulnerability that becomes evident in shameful feelings, such as dislike of breastfeeding, aversion to the milk-producing body and anger towards the child. Anna continued breastfeeding as a way to rid herself of the shame, hoping to be confirmed as a good mother. Such an experience may have negative consequences for the mother-child relationship and it can create fear for future breastfeeding. This study concludes that carers should be aware of individual existential dimensions for breastfeeding mothers.

Vitamin A and systemic inflammation as protective factors in multiple sclerosis.

BACKGROUND: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS). OBJECTIVES: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation. METHODS: We measured Retinol Binding Protein (RBP--a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders. RESULTS: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19-0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14-0.95). CONCLUSIONS: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology.

Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples.

BACKGROUND: The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction between these two factors has been proposed. OBJECTIVES: The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples. METHODS: Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed. RESULTS: The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1(402-502), and domain EBNA-1(385-420); p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found. CONCLUSIONS: We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.

Smoking as a risk factor for multiple sclerosis.

BACKGROUND: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure. OBJECTIVE: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples. METHODS: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression. RESULTS: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0-2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3-3.8). CONCLUSIONS: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

Interaction of adipose-derived stem cells with active and dormant breast cancer cells.

BACKGROUND: Although autologous fat grafting is considered a successful method for the management of contour deformities, the fat graft could potentially induce cancer reappearance by fueling dormant breast cancer cells. Our aim was to characterize the role of adipose-derived stem cells on active and dormant breast cancer cell growth. METHODS: Cobalt chloride was used to induce dormancy in MCF-7 cancer cells. Proliferation of active and dormant cancer cells was determined in the presence of adipose-derived stem cells. A proteome array was used to detect cancer-related protein expression in the cell-conditioned medium. The migration of cancer cells was measured in response to conditioned medium from the adipose-derived stem cells. RESULTS: The adipose-derived stem cells showed variable effects on active MCF-7 cells growth and inhibited MCF-7 proliferation after the withdrawal of cobalt chloride. Of the 84 different proteins measured in the conditioned medium, only tenascin-C was differentially expressed in the co-cultures. MCF-7 cells alone did not express tenascin-C, whereas co-cultures between MCF-7 and adipose-derived stem cells expressed more tenascin-C versus adipose-derived stem cells alone. The conditioned medium from co-cultures significantly increased the migration of the cancer cells. CONCLUSIONS: Adipose-derived stem cells themselves neither increased the growth or migration of cancer cells, suggesting that autologous fat grafting may be oncologically safe if reconstruction is postponed until there is no evidence of active disease. However, interactions between adipose-derived stem cells and MCF-7 cancer cells could potentially lead to the production of factors, which further promote cancer cell migration.

The paradox of being both needed and rejected: the existential meaning of being closely related to a person with bipolar disorder.

The aim of this study was to elucidate the existential meaning of being closely related to a person with bipolar disorder. A qualitative, descriptive, and explorative design with a phenomenological meaning-oriented analysis was used. The findings reveal a paradoxical, existential exposure of close relatives to a person with bipolar disorder, being both needed and rejected whilst being overshadowed by the specific changeable nature of bipolar disorder. Psychiatric health care services are recommended to consider changes in attitudes and structures that may facilitate close relatives' participation in the care and treatment of persons with bipolar disorder.

Relationships first: Formal and informal home care of older adults in Sweden.

To a great extent, older people in Sweden, often with extensive care needs, are cared for in their own home. Support is often needed from both family and professional caregivers. This study aimed to describe and analyse different aspects of health, functioning and social networks, and how they relate to formal and informal care in the home among older adults. Analyses were performed utilising data from the OCTO-2 study, with a sample of 317 people living in Jönköping County, aged 75, 80, 85 or 90 years, living in their own homes. Data were collected with in-person-testing. Based on receipt of care, the participants were divided into three groups: no care, informal care only, and formal care with or without informal care. Descriptive statistics and multinomial regression analysis were performed to explore the associations between received care and different aspects of health (such as multimorbidity, polypharmacy), social networks (such as loneliness, number of confidants) and functioning (such as managing daily life). The findings demonstrate that the majority of the participants received no care at home (61%). Multimorbidity and polypharmacy were more common among those receiving some kind of care in comparison to those who received no care; moreover, those receiving some kind of care also had difficulties managing daily life and less satisfaction with their social networks. The multinomial logistic regression analyses demonstrated that age, functioning in daily life, perceived general health and satisfaction with the number of confidants were related to receipt of care, but the associations among these factors differed depending on the type of care that was received. The results show the importance of a holistic perspective that includes the older person's experiences when planning home care. The results also highlight the importance of considering social perspectives and relationships in home care rather than focusing only on health factors.

Balance in life as a prerequisite for community-dwelling older adults' sense of health and well-being after retirement: an interview-based study.

PURPOSE: This study aimed to describe community-dwelling older adults' perceptions of health and well-being in life after retirement. METHODS: This study is part of a larger project using a mixed-methods design to address lifestyles' influence on community-dwelling older adults' health. Individual semi-structured interviews were conducted with 18 older adults in age 70 to 95 years. Data were analysed according to a phenomenographic approach. RESULTS: The results encompass four categories describing variations in community-dwelling older adults' perceptions of health and well-being after retirement: feeling well despite illness and disease, interacting with and being useful for oneself and others, independently embracing opportunities and engaging in life, and maintaining a healthy lifestyle. CONCLUSIONS: The absence of illness and disease is not a clear prerequisite for a sense of health and well-being. To promote and preserve health and well-being after retirement, older adults strived for-and coached themselves to uphold-a balance in life, focusing on not burdening others. This life orientation after retirement must be acknowledged by society at large, especially from an ageist perspective, and in health and social care to preserve and promote health and well-being.

The intertwining of reconciliation and displacement: a lifeworld hermeneutic study of older adults' perceptions of the finality of life.

PURPOSE: This study aimed to explain and understand the existential meaning of the finality of life from the perspective of healthy older adults. METHOD: Participants were recruited from a major project on older adults' life situations. They were interviewed about their thoughts on the end of life, and their responses were interpreted using a lifeworld hermeneutic approach. RESULTS: The findings showed that thinking about the inevitable finality of life involves feelings of liberation, frightening thoughts, a comforting promise of something beyond death, acceptance of the concept of death as a companion in life and a desire to live. Philosopher Simone de Beauvoir's existential ideas about ageing and death were then used to further explain and understand the meaning of the finality of life and to support a comprehensive understanding. de Beauvoir suggests that when the temporal horizon of existence shrinks, one lives closer to the finality of life. For a comprehensive understanding, attributing meaning to the finality of life required the intertwining of reconciliation and displacement. The interpretations were further discussed using ideas from the fields of existential philosophy and caring science in order to develop a basis for caring practice. CONCLUSIONS: The conclusions suggested that professional health care for older adults would benefit from a lifeworld-led caring science approach that includes readiness for a caring dialogue that focuses on existential issues.

Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination.

Development of T cell-directed immune checkpoint inhibitors (ICI) has revolutionized metastatic melanoma (MM) therapy, but <50% of treated patients experience durable responses. This phase I trial (NCT01946373) investigates the safety/feasibility of tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) combined with dendritic cell (DC) vaccination in MM patients progressing on ICI. An initial cohort (5 patients) received TIL therapy alone to evaluate safety and allow for optimization of TIL expansion protocols. A second cohort (first-in-man, 5 patients) received TIL combined with autologous tumor lysate-loaded DC vaccination. All patients received cyclophosphamide/fludarabine preconditioning prior to, and intravenous (i.v.) IL-2 after, TIL transfer. The DC vaccine was given as five intradermal injections after TIL and IL-2 administration. [18F]-FDG PET/CT radiology was performed to evaluate clinical response, according to RECIST 1.1 (on the CT part). Immunological monitoring was performed by flow cytometry and T-cell receptor (TCR) sequencing. In the safety/optimization cohort, all patients had a mixed response or stable disease, but none durable. In the combination cohort, two patients experienced complete responses (CR) that are still ongoing (>36 and >18 months, respectively). In addition, two patients had partial responses (PR), one still ongoing (>42 months) with only a small bone-lesion remaining, and one of short duration (<4 months). One patient died early during treatment and did not receive DC. Long-lasting persistency of the injected TILs was demonstrated in blood. In summary, we report clinical responses by TIL therapy combined with DC vaccination in 4 out of 4 treated MM patients who previously failed ICI.

Professional aphasia care trusting the patient's competence while facing existential issues.

AIMS AND OBJECTIVES: The aim of this study was to complement 'expert' knowledge about speech-language therapy by studying the phenomenon of professional aphasia care from the patient's perspective. BACKGROUND: The methods for assisting patients with aphasia have mainly been based on speech language therapy with methods for training language. However, the effectiveness of mereley training has not been conclusively proven. In this study, it was assumed that patients with impaired use of language require professional caring interventions as a base for training. DESIGN: A phenomenological approach was used to gain understanding of patients' lived experiences of professional aphasia care. METHOD: Data consisted of eight in-depth interviews, four follow-up interviews, two notes from diaries and two biographies. Data were analysed according to a descriptive phenomenological method. RESULTS: The essential meaning of the phenomenon was: trusting the patient's competence while facing existential issues. To enhance understanding, the essential meaning was specified in terms of the following constituents: preventing isolation, straightforwardness, provision of security, recognition of caring needs, encouraging efforts to practise language, equality and supporting maintenance of identity. CONCLUSIONS: This study adds to the knowledge about speech-language therapy that professional aphasia care presupposes a secure base and a carer who recognises and trusts the patient's ability to think and communicate. RELEVANCE TO CLINICAL PRACTICE: Implications for clinical practice are outlined under the following main headings, a secure caring base, encourage a fighting spirit and expressions of feelings, facilitate communication, try to understand the patient's existential situation and enable patients to recognise that their self-image derives from the painful experience of losing the world of symbols. Inside is the same person and carers should make it clear that they are aware of that.

Cyclooxygenase-2 inhibition suppresses alphavbeta6 integrin-dependent oral squamous carcinoma invasion.

Worldwide oral squamous cell carcinoma (OSCC) represents about 5.5% of all malignancies, with approximately 30,000 new cases each year in the United States. The integrin alpha(v)beta(6) and the enzyme cyclooxygenase-2 (COX-2) are implicated in OSCC progression and have been suggested as possible therapeutic targets. Each protein also is reported to identify dysplasias at high risk of malignant transformation, and current clinical trials are testing the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) at preventing OSCC development. Given the probable increased expression of alpha(v)beta(6) and COX-2 in OSCC and the inhibition of several integrins by NSAIDs, we investigated whether NSAIDs affected alpha(v)beta(6)-dependent cell functions. We found that expression of both alpha(v)beta(6) and COX-2 was significantly higher in OSCC compared with oral epithelial dysplasias. Neither protein preferentially identified those dysplastic lesions that became malignant. Using OSCC cell lines, modified to express varying levels of alpha(v)beta(6), we assessed the effect of COX-2 inhibition on cell invasion. We found that the COX-2 inhibitor NS398 inhibited specifically alpha(v)beta(6)-dependent, but not alpha(v)beta(6)-independent, OSCC invasion in vitro and in vivo, and this effect was modulated through prostaglandin E(2) (PGE(2))-dependent activation of Rac-1. Transient expression of constitutively active Rac-1, or addition of the COX-2 metabolite PGE(2), prevented the anti-invasive effect of NS398. Conversely, RNA interference down-regulation of Rac-1 inhibited alpha(v)beta(6)-dependent invasion. These findings suggest that COX-2 and alpha(v)beta(6) interact in promoting OSCC invasion. This is a novel mechanism that, given the ubiquity of alpha(v)beta(6) expression by head and neck cancers, raises the possibility that NSAIDs could protect against OSCC invasion.

Caring Through Web-Based Communication: A Qualitative Evaluation of a Nursing Intervention to Create Holistic Well-Being Among Patients With Hematological Disease.

PURPOSE: To examine how written communication between patients with hematological diseases and a nurse within a web-based communication service can be caring. DESIGN: The study is based on qualitative deductive content analysis of 109 written messages between 10 patients and a responding nurse. The evaluated nursing intervention is a web-based communication service where patients could request support from a responding nurse during 2 months of use. A structured theoretical matrix based on Swanson's theory of caring including compassion, competence, and upholding trust is used for the analysis. FINDINGS: Nursing compassion emerges when patients share personal matters and the nurse has an opportunity to explicitly display genuine interest and understanding. Nursing competence is required when patients ask for or are in need of information, advice, and emotional support. The nurse can uphold trust when compassion and competence are exhibited and patients share their innermost feelings. CONCLUSIONS: Web-based communication has the potential to contribute to holistic well-being according to Swanson's theory of caring. The written word lasts, can be read repeatedly, and in connection with writing there is time for reflection. However, the lack of nonverbal cues makes it important that the nurse answers in a fully accurate and explicitly caring way.