Not without Context-A Multiple Methods Study on Evaluation and Correction of Automated Brain Tumor Segmentations by Experts.

RATIONALE AND OBJECTIVES: Brain tumor segmentations are integral to the clinical management of patients with glioblastoma, the deadliest primary brain tumor in adults. The manual delineation of tumors is time-consuming and highly provider-dependent. These two problems must be addressed by introducing automated, deep-learning-based segmentation tools. This study aimed to identify criteria experts use to evaluate the quality of automatically generated segmentations and their thought processes as they correct them. MATERIALS AND METHODS: Multiple methods were used to develop a detailed understanding of the complex factors that shape experts' perception of segmentation quality and their thought processes in correcting proposed segmentations. Data from a questionnaire and semistructured interview with neuro-oncologists and neuroradiologists were collected between August and December 2021 and analyzed using a combined deductive and inductive approach. RESULTS: Brain tumors are highly complex and ambiguous segmentation targets. Therefore, physicians rely heavily on the given context related to the patient and clinical context in evaluating the quality and need to correct brain tumor segmentation. Most importantly, the intended clinical application determines the segmentation quality criteria and editing decisions. Physicians' personal beliefs and preferences about the capabilities of AI algorithms and whether questionable areas should not be included are additional criteria influencing the perception of segmentation quality and appearance of an edited segmentation. CONCLUSION: Our findings on experts' perceptions of segmentation quality will allow the design of improved frameworks for expert-centered evaluation of brain tumor segmentation models. In particular, the knowledge presented here can inspire the development of brain tumor-specific metrics for segmentation model training and evaluation.

Blocking Aerobic Glycolysis by Targeting Pyruvate Dehydrogenase Kinase in Combination with EGFR TKI and Ionizing Radiation Increases Therapeutic Effect in Non-Small Cell Lung Cancer Cells.

Increased glycolytic activity is a hallmark of cancer initiation and progression and is often observed in non-small cell lung cancer (NSCLC). Pyruvate dehydrogenase (PDH) complex acts as a gatekeeper between glycolysis and oxidative phosphorylation, and activation of PDH is known to inhibit glycolytic activity. As part of a standard therapeutic regimen, patients with NSCLC harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) are treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). Independent of good initial response, development of resistance to this therapy is inevitable. In the presented work, we propose that inhibition of glycolysis will add to the therapeutic effects and possibly prevent development of resistance against both EGFR TKIs and ionizing radiation in NSCLC. Analysis of transcriptome data from two independent NSCLC patient cohorts identified increased expression of pyruvate dehydrogenase kinase 1 (PDHK1) as well as upregulated expression of genes involved in glucose metabolism in tumors compared to normal tissue. We established in vitro models of development of resistance to EGFR TKIs to study metabolism and determine if targeting PDHK would prevent development of resistance to EGFR TKIs in NSCLC cells. The PDHK1 inhibitor dichloroacetate (DCA) in combination with EGFR TKIs and/or ionizing radiation was shown to increase the therapeutic effect in our NSCLC cell models. This mechanism was associated with redirected metabolism towards pyruvate oxidation and reduced lactate production, both in EGFR TKI sensitive and resistant NSCLC cells. Using DCA, the intracellular pool of pyruvate available for lactic fermentation becomes limited. Consequently, pyruvate is redirected to the mitochondria, and reinforces mitochondrial activity. Addition of DCA to cell culture deacidifies the extracellular microenvironment as less lactate is produced and excreted. In our study, we find that this redirection of metabolism adds to the therapeutic effect of EGFR TKI and ionizing radiation in NSCLC.

Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a well-characterized process of cell plasticity that may involve metabolic rewiring. In cancer, EMT is associated with malignant progression, tumor heterogeneity, and therapy resistance. In this study, we investigated the role of succinate dehydrogenase (SDH) as a potential key regulator of EMT. METHODS: Associations between SDH subunits and EMT were explored in gene expression data from breast cancer patient cohorts, followed by in-depth studies of SDH suppression as a potential mediator of EMT in cultured cells. RESULTS: We found an overall inverse association between EMT and the SDH subunit C (SDHC) when analyzing gene expression in breast tumors. This was particularly evident in carcinomas of basal-like molecular subtype compared to non-basal-like tumors, and a low SDHC expression level tended to have a prognostic impact in those patients. Studies in cultured cells revealed that EMT was induced by SDH inhibition through SDHC CRISPR/Cas9 knockdown or by the enzymatic inhibitor malonate. Conversely, overexpression of EMT-promoting transcription factors TWIST and SNAI2 caused decreased levels of SDHB and C and reduced rates of SDH-linked mitochondrial respiration. Cells overexpressing TWIST had reduced mitochondrial mass, and the organelles were thinner and more fragmented compared to controls. CONCLUSIONS: Our findings suggest that downregulation of SDHC promotes EMT and that this is accompanied by structural remodeling of the mitochondrial organelles. This may confer survival benefits upon exposure to hostile microenvironment including oxidative stress and hypoxia during cancer progression.

Bone Morphogenetic Protein Promotes Lewis X Stage-Specific Embryonic Antigen 1 Expression Thereby Interfering with Neural Precursor and Stem Cell Proliferation.

The glycoprotein Prominin-1 and the carbohydrate Lewis X stage-specific embryonic antigen 1 (LeX-SSEA1) both have been extensively used as cell surface markers to purify neural stem cells (NSCs). While Prominin-1 labels a specialized membrane region in NSCs and ependymal cells, the specificity of LeX-SSEA1 expression and its biological significance are still unknown. To address these issues, we have here monitored the expression of the carbohydrate in neonatal and adult NSCs and in their progeny. Our results show that the percentage of immunopositive cells and the levels of LeX-SSEA1 immunoreactivity both increase with postnatal age across all stages of the neural lineage. This is associated with decreased proliferation in precursors including NSCs, which accumulate the carbohydrate at the cell surface while remaining quiescent. Exposure of precursors to bone morphogenetic protein (BMP) increases LEX-SSEA1 expression, which promotes cell cycle withdrawal by a mechanism involving LeX-SSEA1-mediated interaction at the cell surface. Conversely, interference with either BMP signaling or with LeX-SSEA1 promotes proliferation to a similar degree. Thus, in the postnatal germinal niche, the expression of LeX-SSEA1 increases with age and exposure to BMP signaling, thereby downregulating the proliferation of subependymal zone precursors including NSCs. Stem Cells 2017;35:2417-2429.

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors.

Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells.

The mitochondrial NAD pool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrial NAD is imported from the cytosol by carrier proteins, in mammals, the mechanism of how this organellar pool is generated has remained obscure. A transporter mediating NAD import into mammalian mitochondria has not been identified. In contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is able to catalyze NAD(+) biosynthesis in vitro. However, whether the endogenous NMNAT3 protein is functionally effective at generating NAD(+) in mitochondria of intact human cells still remains to be demonstrated. To modulate mitochondrial NAD(+) content, we have expressed plant and yeast mitochondrial NAD(+) carriers in human cells and observed a profound increase in mitochondrial NAD(+). None of the closest human homologs of these carriers had any detectable effect on mitochondrial NAD(+) content. Surprisingly, constitutive redistribution of NAD(+) from the cytosol to the mitochondria by stable expression of the Arabidopsis thaliana mitochondrial NAD(+) transporter NDT2 in HEK293 cells resulted in dramatic growth retardation and a metabolic shift from oxidative phosphorylation to glycolysis, despite the elevated mitochondrial NAD(+) levels. These results suggest that a mitochondrial NAD(+) transporter, similar to the known one from A. thaliana, is likely absent and could even be harmful in human cells. We provide further support for the alternative possibility, namely intramitochondrial NAD(+) synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria of human cells.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.

BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.

Automated quantification and integrative analysis of 2D and 3D mitochondrial shape and network properties.

Mitochondrial morphology and function are coupled in healthy cells, during pathological conditions and (adaptation to) endogenous and exogenous stress. In this sense mitochondrial shape can range from small globular compartments to complex filamentous networks, even within the same cell. Understanding how mitochondrial morphological changes (i.e. "mitochondrial dynamics") are linked to cellular (patho) physiology is currently the subject of intense study and requires detailed quantitative information. During the last decade, various computational approaches have been developed for automated 2-dimensional (2D) analysis of mitochondrial morphology and number in microscopy images. Although these strategies are well suited for analysis of adhering cells with a flat morphology they are not applicable for thicker cells, which require a three-dimensional (3D) image acquisition and analysis procedure. Here we developed and validated an automated image analysis algorithm allowing simultaneous 3D quantification of mitochondrial morphology and network properties in human endothelial cells (HUVECs). Cells expressing a mitochondria-targeted green fluorescence protein (mitoGFP) were visualized by 3D confocal microscopy and mitochondrial morphology was quantified using both the established 2D method and the new 3D strategy. We demonstrate that both analyses can be used to characterize and discriminate between various mitochondrial morphologies and network properties. However, the results from 2D and 3D analysis were not equivalent when filamentous mitochondria in normal HUVECs were compared with circular/spherical mitochondria in metabolically stressed HUVECs treated with rotenone (ROT). 2D quantification suggested that metabolic stress induced mitochondrial fragmentation and loss of biomass. In contrast, 3D analysis revealed that the mitochondrial network structure was dissolved without affecting the amount and size of the organelles. Thus, our results demonstrate that 3D imaging and quantification are crucial for proper understanding of mitochondrial shape and topology in non-flat cells. In summary, we here present an integrative method for unbiased 3D quantification of mitochondrial shape and network properties in mammalian cells.

Fathers of Children With Type 1 Diabetes: Perceptions of a Father's Involvement From a Health Promotion Perspective.

This study describes how fathers of children diagnosed with type 1 diabetes understand their involvement in their child's daily life from a health promotion perspective. Sixteen Swedish fathers of children living with type 1 diabetes were interviewed. Manifest and latent content analysis was used to identify two themes: the inner core of the father's general parental involvement and the additional involvement based on the child's diabetes. The former was underpinned by the fathers' prioritization of family life and the fathers being consciously involved in raising the child, and the latter by the fathers promoting and controlling the child's health and promoting and enabling the child's autonomy. The results highlight that the quality of the fathers' involvement is essential in the management of a child's chronic illness. It is important for pediatric diabetes health care professionals to assess the quality of fathers' involvement to promote the child's health.

Reducing errors through a web-based self-management support system.

Web-based self-management support systems SMSS, can successfully assist a wide range of patients with information and self-management support. O or as a stand-alone service, are e-messages. This study describes how one component of a multi component SMSS, an e-message service, in which patients with breast cancer could direct questions to nurses, physicians or social workers at the hospital where they were being treated, had an influence on safety and continuity of care. Ninety-one dialogues consisting of 284 messages were analysed. The communications between patients and the healthcare team revealed that the e-messages service served as a means for quality assurance of information, for double-checking and for coordination of care. We give examples of how an e-mail service may improve patients' knowledge in a process of taking control over their own care - increasingly important in a time of growing complexity and specialization in healthcare. It remains to be tested whether an e-message service can improve continuity of care and prevent or mitigate medical mishaps.

Regulation and quantification of cellular mitochondrial morphology and content.

Mitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice.

The activation of epidermal growth factor receptor (EGFR) affects multiple aspects of neural precursor behaviour, including proliferation and migration. Telencephalic precursors acquire EGF responsiveness and upregulate EGFR expression at late stages of development. The events regulating this process and its significance are still unclear. We here show that in the developing and postnatal hippocampus (HP), growth/differentiation factor (GDF) 15 and EGFR are co-expressed in primitive precursors as well as in more differentiated cells. We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires active CXC chemokine receptor (CXCR) 4. Besides EGFR expression, GDF15 ablation also leads to decreased proliferation and migration. In particular, lack of GDF15 impairs both processes in the cornu ammonis (CA) 1 and only proliferation in the dentate gyrus (DG). Importantly, migration and proliferation in the mutant HP were altered only perinatally, when EGFR expression was also affected. These data suggest that GDF15 regulates migration and proliferation by promoting EGFR signalling in the perinatal HP and represent a first description of a functional role for GDF15 in the developing telencephalon.

Proliferation and cilia dynamics in neural stem cells prospectively isolated from the SEZ.

Neural stem cells (NSCs) generate new neurons in vivo and in vitro throughout adulthood and therefore are physiologically and clinically relevant. Unveiling the mechanisms regulating the lineage progression from NSCs to newborn neurons is critical for the transition from basic research to clinical application. However, the direct analysis of NSCs and their progeny is still elusive due to the problematic identification of the cells. We here describe the isolation of highly purified genetically unaltered NSCs and transit-amplifying precursors (TAPs) from the adult subependymal zone (SEZ). Using this approach we show that a primary cilium and high levels of epidermal growth factor receptor (EGFR) at the cell membrane characterize quiescent and cycling NSCs, respectively. However, we also observed non-ciliated quiescent NSCs and NSCs progressing into the cell cycle without up-regulating EGFR expression. Thus, the existence of NSCs displaying distinct molecular and structural conformations provides more flexibility to the regulation of quiescence and cell cycle progression.

Assessing sample and miRNA profile quality in serum and plasma or other biofluids.

MicroRNAs (miRNAs) constitute a class of small cellular RNAs (typically 21-23nt) that function as post-transcriptional regulators of gene expression. Current estimates indicate that more than one third of the cellular transcriptome is regulated by miRNAs, although they are relatively few in number (less than 2000 human miRNAs). The high relative stability of miRNA in common clinical tissues and biofluids (e.g. plasma, serum, urine, saliva, etc.) and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNA quantification as a promising new tool for a wide range of diagnostic applications. Furthermore miRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. To facilitate discovery and clinical development of miRNA-based biomarkers, we developed a genome-wide Locked Nucleic Acid (LNA™)-based miRNA qPCR platform with unparalleled sensitivity and robustness. The platform allows high-throughput profiling of miRNAs from important clinical sources without the need for pre-amplification. Using this system, we have profiled thousands of biofluid samples including blood derived plasma and serum. An extensive quality control (QC) system has been implemented in order to secure technical excellence and reveal any unwanted bias coming from pre-analytical or analytical variables. We present our approaches to sample and RNA QC as well as data QC and normalization. Specifically we have developed normal reference ranges for circulating miRNAs in serum and plasma as well as a hemolysis indicator based on microRNA expression.

[Use of ambulatory blood pressure measurement in primary care in Iceland]. / Notkun sólarhringsblódthrýstingsmælinga í heilsugæslu.

OBJECTIVE: To study the use of ambulatory blood pressure measurement (ABPM) in primary care in Iceland. MATERIAL AND METHODS: All patients who had ABPM done during the period from 1st of June 2008 till 31st of May 2010 at three health care centers comprised the study group. Medical records of these patients were examined and information about previous diagnosis of hypertension, cardiovascular disease, diabetes, obesity, smoking habits and drug prescriptions along with results of blood pressure measurements were registrated. RESULTS: A total of 205 ABPM were done during the study period. Mean age of the patients was 54 years ±15.1, the youngest being 18 and the oldest 87 years old. The study group comprised 119 (58%) women and 86 men (42%). The ABPM was done as a part of follow-up of hypertension in 112 (55%) cases, but among 93 patients it was used as an aid in the diagnosis of hypertension. The study showed that 88 (41%) were defined as dippers. The ABPM did not result in a change of treatment in 14% of cases, among 19% of subjects antihypertensive treatment was initiated whereas 16% did not require any treatment; in 6% of cases the antihypertensive treatment was reduced while in 13% it was necessary to increase the treatment. CONCLUSION: We conclude that ABPM is a very useful tool in primary care settings, both to improve diagnosis and the treatment of hypertension.

A phase II multi-center study of triple therapy with paclitaxel, S-1 and cisplatin in patients with advanced gastric cancer.

OBJECTIVES: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. METHODS: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle. RESULTS: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. CONCLUSIONS: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.

The concept of ''equity'' in health-promotion articles by Nordic authors - a matter of some confusion and misconception.

AIMS: This paper focuses on equity in health, one of the key principles of the Ottawa Charter. It aims at analysing and discussing how the concept was defined, applied, and integrated in health-promotion articles by authors with a Nordic affiliation. METHODS: Abstracts were first identified by the search word ''health promotion'' as a key word. The search was limited to 1986-2008 and abstracts written in English by authors with a Nordic affiliation. Abstracts/articles for the present study were subsequently selected from these abstracts using the search word ''equity'' and analysed by quantitative and qualitative content analysis. FINDINGS: A majority of the 18 articles in the study did not include any proper definition of the term ''equity in health''. Most articles dealt with health in general or ''Health for All'' aspects and did not focus on specific strategies for vulnerable individuals or groups. The theoretical papers had a clear focus on equity aspects even though the concept of equity was sometimes included in an implicit way. In contrast, most papers reporting empirical studies did not specifically target equity aspects. Instead, the analysis gave the impression that many authors used the term ''equity'' synonymously with ''equality in health''. CONCLUSIONS: The findings may indicate that the concept of ''equity in health'' has been attenuated or even forgotten by Nordic health-promotion researchers and needs to be re-established as a strong concern within health promotion.

Global analysis of the relationship between JIL-1 kinase and transcription.

The ubiquitous tandem kinase JIL-1 is essential for Drosophila development. Its role in defining decondensed domains of larval polytene chromosomes is well established, but its involvement in transcription regulation has remained controversial. For a first comprehensive molecular characterisation of JIL-1, we generated a high-resolution, chromosome-wide interaction profile of the kinase in Drosophila cells and determined its role in transcription. JIL-1 binds active genes along their entire length. The presence of the kinase is not proportional to average transcription levels or polymerase density. Comparison of JIL-1 association with elongating RNA polymerase and a variety of histone modifications suggests two distinct targeting principles. A basal level of JIL-1 binding can be defined that correlates best with the methylation of histone H3 at lysine 36, a mark that is placed co-transcriptionally. The additional acetylation of H4K16 defines a second state characterised by approximately twofold elevated JIL-1 levels, which is particularly prominent on the dosage-compensated male X chromosome. Phosphorylation of the histone H3 N-terminus by JIL-1 in vitro is compatible with other tail modifications. In vivo, phosphorylation of H3 at serine 10, together with acetylation at lysine 14, creates a composite histone mark that is enriched at JIL-1 binding regions. Its depletion by RNA interference leads to a modest, but significant, decrease of transcription from the male X chromosome. Collectively, the results suggest that JIL-1 participates in a complex histone modification network that characterises active, decondensed chromatin. We hypothesise that one specific role of JIL-1 may be to reinforce, rather than to establish, the status of active chromatin through the phosphorylation of histone H3 at serine 10.

Holism in nursing and health promotion: distinct or related perspectives?--A literature review.

BACKGROUND: The concept of holism is central in health promotion as well as in nursing. Holism or a holistic view on health was identified as one of the key principles of the Ottawa Charter for Health Promotion and is linked to social ecology and the determinants of health. AIMS: To explore how the term holism was defined and/or described in Nordic articles with a health-promotion approach, and how holism aspects were related to nursing and health promotion, and to the other key principles of the Ottawa Charter. METHODS: Abstracts were first identified by the search word 'health promotion' as a keyword. The search was limited to 1986-2008 and abstracts written in English by authors with a Nordic affiliation. Abstracts/articles for this study were subsequently selected from these abstracts using the search words 'holism' and 'holistic' and analysed by quantitative and manifest qualitative content analysis. FINDINGS: The sample included 23 articles: one theoretical, two reviews and 20 empirical studies. Sixteen articles included a hospital setting or nursing perspective. A holistic perspective could be extracted from most articles. No larger but several minor differences were identified in the way holism aspects were related to nursing and health promotion respectively. CONCLUSION: There is a risk that the individual patient perspective of holism in nursing may result in less chance of reaching larger groups of patients with chronic diseases and mental health problems, not least the most vulnerable ones.

Overweight children's response to an annual health dialogue with the school nurse.

The objective of this study was to compare overweight and normal weight pupils' perceived outcome of the health dialogue with the school nurse. A random sample of schools in Denmark, where pupils age 11.6, 13.6 and 15.6 years old, answered a questionnaire (response rate 88%, n = 5205). The independent variable weight group was measured by self-reported height and weight and calculated as body mass index. Perceived outcome of the dialogue was measured as: (i) reflected on the dialogue; (ii) discussed the content with parents; (iii) followed the advice of the nurse; and (iv) visited the nurse again. Overweight boys reflected (odds ratio (OR) = 1.73), discussed the dialogue with at least one parent (OR = 1.38), followed the nurse's advice (OR = 1.42) and visited the nurse again (OR = 2.68). There was a significant statistical link between age group and perceived outcome among the boys, but not girls. The 11-year-old overweight boys perceived more positive effects from the dialogue with the school nurse.