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This paper aims to focus on how family and community in Greenland perceive support- giving during the perinatal period. It explores Greenlanders use of storytelling as a health-promoting tool in the perinatal period. It is research set in Greenland, but analysed in a larger context. Using an ethnographic approach to subject matter, the paper is based on a series of qualitative interviews and focus groups conducted between 2003 and 2011 with mothers and fathers. Ethnographic content analysis, interviews and dialogues with Culture Bearers were used to analyse and set the stories into a cultural perspective. The child was described as the centre of the family and the family as the bedrock of life. The mothers, fathers and Culture Bearers presented three main concepts in their stories: 1) my family @@@ a safe harbour, 2) the child as the centre of the family, and 3) the equal sharing of burden and joy. [ABSTRACT FROM AUTHOR]

Scand J Caring Sci; 2011; 25; 798-805 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Borup IK, Holstein BE. International Journal of Nursing Practice 2010; 16: 359–365 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. [ABSTRACT FROM AUTHOR]

The dosage compensation complex (DCC) in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high- and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs. [ABSTRACT FROM AUTHOR]

Abstract: Dosage compensation involves fine-tuning of gene expression at the level of entire chromosomes. The principles that assure selective targeting of the male X chromosome in Drosophila and the mechanism by which transcription levels are adjusted in a twofold range are still mysterious. We discuss the prevalent models in the context of recent experimental observations. [Copyright &y& Elsevier]

For some solid metal–liquid metal couples that exhibit liquid metal embrittlement, penetration of the embrittling liquid metal along grain boundaries of the solid metal is observed. Penetration speed of liquid gallium into aluminum and that of mercury into silver and copper were measured by using thin evaporated films. The degree of embrittlement induced by the liquid metal was estimated by tensile tests. The tensile specimens were kept in contact with the liquid metal for various times of exposure, and then the embrittler was removed before the test. When the exposure time is short, no sign of embrittlement is observed. As the exposure time increases further, the brittle fracture surface area increases with logarithm of the exposure time. The results imply the existence of an incubation period, which is inversely proportional to the penetration speed of embrittling liquid metal. [Copyright &y& Elsevier]

Twofold differences in gene expression levels can be vital for an organism. This is beautifully illustrated by the process of `dosage compensation'' in Drosophila, which doubles transcription from the single male X chromosome to equal the mRNA levels originating from the two X chromosomes in female cells. Failure of the process leads to male-specific lethality. A number of recent publications have furthered our understanding of the ribonucleoprotein complex, which mediates dosage compensation and how it targets the male X chromosome. Deciphering the principles of X chromosome recognition and the nature of the chromatin configuration, that allows fine-tuning of transcription, remain the most interesting challenges. [Copyright &y& Elsevier]

Background: Little information is currently available on the contribution of locally generated inflammatory and chemotactic cytokines to endothelial cell activation and subsequent neutrophil transendothelial migration in patients with Helicobacter pylori ( H. pylori )-associated gastritis. Methods: The contents of interleukin (IL)-1β and IL-8 in the organ culture supernatants of antral mucosal tissues were measured with an enzyme-linked immunosorbent assay. The effects of the endogenous IL-1β and IL-8 in mucosal tissues on neutrophil adherence and transendothelial migration were investigated using an experimental model of human umbilical vein endothelial cells (HUVEC). Results: The contents of IL-1β and IL-8 in organ cultures of antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. The organ culture supernatants from H. pylori -positive patients induced the expression of intercellular adhesion molecule-1 mRNA in HUVEC with increased binding of neutrophils, and these stimulatory effects were inhibited when HUVEC were pretreated with a nuclear factor-κB inhibitor, MG-132. Moreover, neutrophil adherence to HUVEC induced by the supernatants decreased after preincubation with neutralizing anti-IL-1β antibody. As compared with the supernatants from H. pylori -negative patients, the samples from H. pylori -positive patients exhibited a significantly higher chemotactic activity for neutrophils, which was inhibited almost completely by preincubation of the supernatants with anti-IL-8 antibody. Conclusions: Locally generated IL-1β and IL-8 could coordinate with each other during the process of neutrophil infiltration into the gastric mucosa in patients with H. pylori infection. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the relative contribution of peptide growth factors and leukocyte-derived proteinases to the repair processes in inflammatory bowel disease (IBD). We investigated their possible roles in epithelial cell restitution and proliferation in patients with IBD.Methods: The expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor-beta (TGF-beta), and neutrophil elastase (NE) was examined in colonic mucosal tissues. The effects of organ culture supernatants of mucosal tissues on epithelial cell restitution and proliferation were analyzed in vitro using an intestinal cell line, IEC-6 cells.Results: Most organ cultures detected the presence of measurable levels of HGF, with a relative paucity of KGF and TGF-beta activity. Greater levels of HGF were obtained in the mucosa involved with IBD, especially in patients with ulcerative colitis (UC). The mucosa involved with UC also showed higher amounts of NE. The supernatants from the mucosa involved with UC possessed a prominent stimulatory effect on the restitution of IEC-6 cells. By contrast, significant suppression beyond baseline levels was observed for the proliferation of IEC-6 cells when they were incubated with recombinant HGF plus the supernatants from the mucosa involved with UC. This suppression was diminished considerably by preincubation of the supernatants with the anti-NE antibody.Conclusions: HGF produced in the intestinal mucosa may be an important stimulator acting on epithelial cell restitution in patients with IBD. However, NE released in situ may impair mucosal repair through inhibiting epithelial cell proliferation in patients with UC. [ABSTRACT FROM AUTHOR]

Background: Excessive upregulation of gastric epithelial cell apoptosis is speculated to be associated with ulcerogenesis in Helicobacter pylori-positive peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction of gastric epithelial cell apoptosis mediated by infiltrating T cells and their soluble products. Methods: The contents of soluble Fas ligand (sFasL) and interferon-γ (IFN-γ) in organ cultures and the degree of apoptosis and the expression of apoptosis-related proteins in the gastric epithelium were examined using the mucosal tissues obtained from the antrum and the ulcer site in patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of gastric epithelial cell apoptosis induced by sFasL and IFN-γ were analyzed using epithelial cell lines, MKN 45 and KATO III. Results: The mucosal tissues of the ulcer site had substantially higher contents of sFasL and IFN-γ in organ cultures regardless of its healing stage in association with increased numbers of apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in the surface foveolar epithelium as compared with the antral tissues in patients with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN-γ-treated cells had more prominent effects than untreated cells. The expression of Bak in MKN 45 cells increased when they were treated with IFN-γ. Conclusions: Upregulation of mucosal sFasL and IFN-γ may be involved in ulcerogenesis in patients with H. pylori-positive GU through induction of gastric epithelial cell apoptosis. [ABSTRACT FROM AUTHOR]

Background: Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori ) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram-negative micro-organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM. Methods: The H. pylori strain 26695 and three CAM-resistant clinical isolates were cultured in broth with and without CAM (2–500 ng/mL). Expression of H. pylori proteins was examined by two-dimensional (2D)-electrophoresis followed by N-terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy. Results: 2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30–500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections. Conclusions: CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up-regulation of the release of HspB from the bacteria in infected patients. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this paper is to achieve a deeper understanding of the learning processes that occur within a regular health dialogue between pupils and school health nurse from the school health nurse’s perspective. The study used a grounded theory approach for the data collection and analysis. Eight experienced school health nurses were interviewed using a semistructured ‘interview guide’. The interviews were audio recorded and transcribed verbatim. A detailed analysis presented the processes involved and the core category emerged as creating a communicative room to learn about health. The core category contained factors related to competencies, authenticity, reflective openness and environmental support, which was the basis for learning processes and a successful health dialogue. This paper adds to our understanding of the processes in school health nursing and the learning about health which takes place within a health dialogue. [ABSTRACT FROM AUTHOR]

Background: Although αtilde-chemokines, such as interleukin (IL)-8 and epithelial neutrophil-activating peptide 78, are implicated in the pathogenesis of inflammatory bowel disease (IBD), little information is currently available on the expression and cellular source of growth-related gene product-α (GROα) and its functional relationship to other αtilde-chemokines in the intestinal mucosa of patients with IBD. Methods: The contents of IL-8 and GROα in organ cultures, the expression of IL-8 and GROα mRNA, and the modulatory effects of inflammatory mediators on IL-8 and GROα-producing cells were examined using colonic mucosal tissues. In vitro stimulatory effects of IL-8 and GROα on neutrophils were investigated in terms of chemotactic migration and superoxide anion generation. Results: The contents of IL-8 and GROα in organ cultures were elevated in patients with IBD, especially in those with active ulcerative colitis (UC). Both IL-8 and GROα contents increased according to an increase in histological disease activity in patients with UC, but not in those with Crohn disease. In contrast, no significant correlation was found between the contents of these α-chemokines and clinical disease activity. In situ hybridization detected increased expression of IL-8 and GROα mRNA in macrophages, pericrypt myofibroblasts, and the epithelium of tissue specimens with active lesions of IBD. The secretion of IL-8 and GROα from macrophages and myofibroblasts obtained from control patients was upregulated by inflammatory cytokines and bacterial products. The concentrations of recombinant (r)-IL-8, which covered the levels of activity detected in individual organ cultures or cell cultures of fractionated mucosal cells, could induce chemotactic migration and superoxide anion generation in neutrophils in vitro, and r-GROα had synergistic effects on r-IL-8-induced neutrophil activation. Conclusions: A coordinate upregulation of IL-8 and GROα may be involved in the tissue injury in patients with IBD through their stimulatory effects on neutrophils. [ABSTRACT FROM AUTHOR]

Abstract. Positional cloning continues to be an essential method for gene identification and characterisation. The introduction of PCR-based techniques such as Amplified Fragment Length Polymorphism (AFLP), Simple Sequence Length Polymorphisms (SSLP) and Cleaved Amplified Polymorphic Sequences (CAPS) has greatly increased the efficiency of gene mapping in arabidopsis. To develop the CAPS marker approach further, we have altered several critical mapping parameters. Efficiency was improved by using a small volume of dry seed for DNA extraction instead of the commonly used vegetative tissue. Reproducibility of PCR reactions was enhanced by faster and reduced protocols for PCR and restriction enzyme digestion and optimisation of PCR conditions for over 50 CAPS primer pairs. Finally, the density of genetic markers was increased by providing polymorphic information for all CAPS markers in arabidopsis ecotypes Wassilewskija (Ws), Columbia (Col) and Cape Verde Islands (Cvi). [ABSTRACT FROM AUTHOR]

Presents a study that identified how environmental factors are perceived by pupils with health dialogue. Importance of school satisfaction in pupils; Aim of the health dialogue; Material and methods used in the study; Results of the study.

This study describes and analyses the health dialogue on the basis of the pupils' experience and the association with background factors such as age, sex, geographical areas, family and social class. The theoretical framework is based on empowerment and health promotion, and on Kolb's theory of experiential learning. The study, conducted in 1991, is the Danish contribution to the WHO collaborative study 'Health Behaviour in School Children'. A nationwide random sample of pupils aged 11, 13 and 15 (n = 1860) answered a standardized questionnaire about perceived health, health behaviour, social situation and the health dialogue with the school health nurse. Among the pupils, 68% had participated in the annual health dialogue at the time of the survey (three quarters of the way through the school year). The youngest pupils, and the girls, often participated in groups and reported the greatest number of topics discussed. The health dialogue most frequently comprised 11–20 topics. Most topics discussed were related to health promotion, 31%–60% were related to prevention of illness and symptoms and the rest were related to psychosocial issues. Girls more often reported discussing personal relationships and boys more often discussed action-related topics. Pupils from lower social classes more frequently reported topics related to prevention of illness and symptoms and psychosocial issues. The discussions are the first step in a learning process as a Concrete Experience (CE). [ABSTRACT FROM AUTHOR]

The mitochondrialNADpool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrialNADis 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 mitochondrialNAD+ 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Enhanced gastric mucosal chemokine activity has been demonstrated in patients with Helicobacter pylori infection. However, little is known about the mechanisms involved in this phenomenon. To examine whether in vivo chemokine activity is similar to in vitro response of gastric epithelial cells infected by H. pylori. In organ cultures of mucosal tissues, the levels of interleukin-8 and growth-related gene product α were elevated in patients with peptic ulcer disease compared with those with erosive gastritis or endoscopically normal mucosa. However, there were no significant differences in vitro cultures of MKN45 or KATO III cells that were infected with H. pylori isolated from these same patients. These in vivo and in vitro α-chemokine levels showed no significant association with the presence of cagA gene and CagA protein, ureB genotype, or binding capacity to MKN45 or KATO III cells in individual H. pylori isolates. In contrast, in vivo mucosal α-chemokine activity correlated with H. pylori colonization density. Mucosal chemokine profiles and inflammatory responses in H. pylori infection may be associated more closely with host factors, including those determining bacterial adhesiveness, than with differences in H. pylori strains. [ABSTRACT FROM AUTHOR]

An abstract of the article "Diagnostic capability of CMR for the diagnosis of acute myocarditis in young patients is determined by the presence of elevated cardiac enzymes," by Ina K. Wenzelburger and colleagues is presented.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohn's disease. Cytokines such as tumour necrosis factor-alpha are well-known mediators of the immune system, and treatment with a chimeric anti-tumour necrosis factor-alpha antibody (infliximab) has been shown to be highly effective in patients with Crohn's disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximab's effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes. Methods Thirteen patients with Crohn's disease were treated with infliximab at a dosage of 5-mg/kg body weight. Clinical response was evaluated using the Crohn's Disease Activity Index, and serum soluble interleukin-2 receptor, interleukin-6, tumour necrosis factor-alpha levels were analysed by enzyme-linked immunosorbent assay at 0 and 2 weeks after treatment. Apoptosis of peripheral and lamina propria T lymphocytes after culture with infliximab was detected by flow cytometry. Results Crohn's Disease Activity Index decreased in 12 of 13 patients, and serum soluble interleukin-2 receptor, interleukin-6 and tumour necrosis factor-alpha levels decreased in most patients after treatment with infliximab. Tumour necrosis factor-alpha level before treatment in the six patients in whom Crohn's Disease Activity Index decreased by more than 70 was <5 ng/mL. Infliximab induced the apoptosis of lamina propria but not of peripheral T lymphocytes. Conclusion These findings suggest that a low level of serum tumour necrosis factor-alpha is an indicator for infliximab treatment. The induction of apoptosis of lamina propria T lymphocytes by infliximab may be an important mechanism of its anti-inflammatory effect in patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

Background and Aims The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohn's disease. Cytokines such as tumour necrosis factor-alpha are well-known mediators of the immune system, and treatment with a chimeric anti-tumour necrosis factor-alpha antibody (infliximab) has been shown to be highly effective in patients with Crohn's disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximab's effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes. Methods Thirteen patients with Crohn's disease were treated with infliximab at a dosage of 5-mg/kg body weight. Clinical response was evaluated using the Crohn's Disease Activity Index, and serum soluble interleukin-2 receptor, interleukin-6, tumour necrosis factor-alpha levels were analysed by enzyme-linked immunosorbent assay at 0 and 2 weeks after treatment. Apoptosis of peripheral and lamina propria T lymphocytes after culture with infliximab was detected by flow cytometry. Results Crohn's Disease Activity Index decreased in 12 of 13 patients, and serum soluble interleukin-2 receptor, interleukin-6 and tumour necrosis factor-alpha levels decreased in most patients after treatment with infliximab. Tumour necrosis factor-alpha level before treatment in the six patients in whom Crohn's Disease Activity Index decreased by more than 70 was <5 ng/mL. Infliximab induced the apoptosis of lamina propria but not of peripheral T lymphocytes. Conclusion These findings suggest that a low level of serum tumour necrosis factor-alpha is an indicator for infliximab treatment. The induction of apoptosis of lamina propria T lymphocytes by infliximab may be an important mechanism of its anti-inflammatory effect in patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

The Drosophila trithorax group gene kismet (kis) was identified in a screen for extragenic suppressors of Polycomb (Pc) and subsequently shown to play important roles in both segmentation and the determination of body segment identities. One of the two major proteins encoded by kis (KIS-L) is related to members of the SW12/SNF2 and CHD families of ATP-dependent chromatin-remodeling factors. To clarify the role of KIS-L in gene expression, we examined its distribution on larval salivary gland polytene chromosomes. KIS-L is associated with virtually all sites of transcriptionally active chromatin in a pattern that largely overlaps that of RNA Polymerase II (Pol II). The levels of elongating Pol II and the elongation factors SPT6 and CHD1 are dramatically reduced on polytene chromosomes from kis mutant larvae. By contrast, the loss of KIS-L function does not affect the binding of PC to chromatin or the recruitment of Pol II to promoters. These data suggest that KIS-L facilitates an early step in transcriptional elongation by Pol II. [ABSTRACT FROM AUTHOR]

Hayasaki N, Ito M, Suzuki T, Ina K, Ando T, Kusugami K&Goto H(2004)Histopathology45,377–383Neutrophilic phlebitis is characteristic of intestinal Behçet's disease and simple ulcer syndrome: To characterize the histological features of intestinal Behçet's disease and simple ulcer syndrome and to clarify the possible mechanisms involved in their development by analysing the type of inflammatory infiltrates in the diseased intestine and the expression of adhesion molecules on endothelial cells.: Tissue samples from 10 patients diagnosed as having intestinal Behçet's disease or simple ulcer syndrome were studied. Immunohistochemical studies were performed on paraffin-embedded tissue using a labelled streptavidin–biotin method. In all cases, phlebitis was remarkably seen in submucosal inflammatory lesions, but the adjacent arteries were not affected. Inflammatory infiltrates around the affected vessels consisted of neutrophils and mononuclear cells, and neutrophils predominated over CD68+ macrophages and lymphocytes. The majority of mononuclear cells were CD3+ T cells, and CD4+ cells were more frequent than CD8+ T cells. As for adhesion molecule expression, intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1, was expressed in most endothelial cells of the vessels with phlebitis, some of which were also positive for HLA-DR.: Neutrophilic phlebitis may be involved in the pathogenesis of intestinal Behçet's disease and simple ulcer syndrome. [ABSTRACT FROM AUTHOR]

: Failure of Helicobacter pylori eradication occurs frequently despite use of multiple microbial agents. : We aimed to study differences between H. pylori strains isolated before and after eradication failure. : We treated 87 patients with peptic ulcer using triple therapy consisting of omeprazole plus combinations of clarithromycin, amoxicillin, or metronidazole. We studied the status of cagA, vacA, and iceA by PCR, and examined the differences in H. pylori isolates by pulsed-field gel electrophoresis and arbitrary primer polymerase chain reaction. The minimum inhibitory concentration of clarithromycin, amoxicillin, or metronidazole was determined by an agar dilution method. : Eradication therapy failed in 12 patients (14%); H. pylori isolates were obtained from all of these both before and after therapy. After eradication therapy, 10 patients were colonized with the same strain as before therapy, while the other two patients were colonized with different strains from those before therapy. In the former group, one isolate changed from metronidazole-sensitive to -resistant, one changed from clarithromycin- and metronidazole-sensitive to -resistant, and four were resistant to clarithromycin or metronidazole both before and after therapy. The other four isolates remained sensitive to clarithromycin and metronidazole after therapy. In the two patients who yielded apparently different isolates after therapy, they changed from clarithromycin- and metronidazole-sensitive to -resistant. : Eradication of H. pylori by first-line therapy is an important goal in the treatment of H. pylori-positive peptic ulcer, and that appropriate antimicrobial sensitivity testing should be conducted in patients with eradication failure. [ABSTRACT FROM AUTHOR]

Background: Although increased levels of interleukin (IL)-8 are known to be associated with infiltration of neutrophils in the gastric mucosa with Helicobacter pylori infection, no study has investigated the relationship between local IL-8 levels and neutrophil infiltration in the duodenal mucosa of patients with duodenal ulcer (DU). Methods: Duodenal mucosal biopsy specimens with and without gastric metaplasia (GM) were obtained from patients with DU and controls with an endoscopic methylene blue (MB) staining method. Levels of IL-8 secreted in the organ cultures of biopsy specimens were measured with an enzyme-linked immunosorbent assay. The number of myeloperoxidase-positive neutrophils infiltrating the lamina propria was determined in immunohistochemically stained tissue sections. Results: Histologic assessment showed that there was a strong correlation between the absence of endoscopic MB staining and the extent of GM. The levels of IL-8 in both duodenal and antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. In patients with DU the duodenal mucosal tissues with GM (MB-unstained mucosa) showed significantly higher levels of IL-8 than those without GM (MB-stained mucosa) or the antral mucosa. The number of neutrophils showed similar variations among DU and control patients with a positive correlation with IL-8 activity. The levels of IL-8 and the number of neutrophils decreased after H. pylori eradication in both duodenal and antral mucosal tissues, and these changes were more remarkable in the duodenal mucosal tissues with GM. Conclusions: Increased IL-8 activity in the duodenal mucosa with GM may be important for ulcerogenesis in H. pylori-positive DU patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) patients harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) inevitably develop resistance to targeted EGFR tyrosine kinase inhibitors (TKI) therapy. To support malignant features associated with cancer development and therapy resistance, the cancer cells adapt their metabolic rate and pathways. As an example, aerobic glycolysis, where the cells use glycolysis in the presence of oxygen, is frequently seen. Here we show that targeting aerobic glycolysis represents a promising strategy in cancer therapeutics. 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. [ABSTRACT FROM AUTHOR]

Abstract: microRNAs are small regulatory RNAs that are currently emerging as new biomarkes for cancer and other diseases. In order for biomarkers to be useful in clinical settings, they should be accurately and reliably detected in clinical samples such as formalin-fixed paraffin-embedded (FFPE) sections and blood serum or plasma. These types of samples represent a challenge in terms of microRNA quantification. A newly developed method for microRNA qPCR using LNA™-enhanced primers enables accurate and reproducible quantification of microRNAs in scarce clinical samples. Here we show that LNA™-based microRNA qPCR enables biomarker screening using very low amounts of total RNA from FFPE samples and the results is compared to microarray analysis. We also present evidence that the addition of a small carrier RNA prior to total RNA extraction, improves microRNA quantification in blood plasma and laser capture microdissected sections of FFPE samples. [Copyright &y& Elsevier]