Now showing items 1-20 of 230
Next Page| Abstract: | The use of increasingly complex payment schemes in primary care may represent a barrier to recruiting general practitioners (GP). The existing Norwegian remuneration system is fully activity based - 2/3 fee-for-service and 1/3 capitation. Given that the system has been designed and revised in close collaborations with the medical association, it is likely to correspond - at least to some degree - with the preferences of current GPs (men in majority). The objective of this paper was to study which preferences that young doctors (women in majority), who are the potential entrants to general practice have for activity based vs. salary based payment systems. In November-December 2010 all last year medical students and all interns in Norway (n = 1.562) were invited to participate in an online survey. The respondents were asked their opinion on systems of remuneration for GPs; inclination to work as a GP; risk attitude; income preferences; work pace tolerance. The data was analysed using one-way ANOVA and multinomial logistic regression analysis. A total of 831 (53%) responded. Nearly half the sample (47%) did not consider the remuneration system to be important for their inclination to work as GP; 36% considered the current system to make general practice more attractive, while 17% considered it to make general practice less attractive. Those who are attracted by the existing system were men and those who think high income is important, while those who are deterred by the system are risk averse and less happy with a high work pace. On the question of preferred remuneration system, half the sample preferred a mix of salary and activity based remuneration (the median respondent would prefer a 50/50 mix). Only 20% preferred a fully activity based system like the existing one. A salary system was preferred by women, and those less concerned with high income, while a fully activity based system was preferred by men, and those happy with a high work pace. Given a concern about low recruitment to general practice in Norway, and the fact that an increasing share of medical students is women, we were interested in the extent to which the current Norwegian remuneration system correspond with the preferences of potential GPs. This study suggests that an existing remuneration mechanism has a selection effect on who would like to become a GP. Those most attracted are income motivated men. Those deterred are risk averse, and less happy with a high work pace. More research is needed on the extent to which experienced GPs differ along the questions we asked potential GPs, as well as studying the relative importance of other attributes than payment schemes. |
| URI: | http://hdl.handle.net/10037/4994 |
| Abstract: | There is a deficiency of data on oral health of adults in northern Norway, and available reports indicate poorer oral health in the north as compared with the rest of the country. The objective of this pilot study was to develop and test out tools for a larger epidemiological study of oral health among adults in northern Norway. The study was conducted in the municipalities of Nordkapp and Båtsfjord located in the northernmost county, Finnmark. Questionnaires and letters of invitation were sent to 100 randomly selected individuals in each town, in total 200. Those who filled and returned the questionnaires were sent appointment cards to a free oral examination at the local dental clinic. The main finding from the study was a low response rate; 34% responded to the questionnaire and 26.5% attended the oral examination. Response rate was highest among women above forty years old (37%) and lowest among men under forty years (12%). There is a necessity for further studies and strategies to increase response rate to subsequent oral epidemiologic studies in northern Norway. Radiological examination is not necessary for such studies but a questionnaire and a physical oral examination should be included. |
| URI: | http://hdl.handle.net/10037/4995 |
| Abstract: | Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side. |
| URI: | http://hdl.handle.net/10037/4428 |
| Abstract: | The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKC?/? and PKC? serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKC?/? as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKC?/?. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.Transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs |
| URI: | http://hdl.handle.net/10037/3953 |
| Description: | This article is part of Mohammad Belal Aljabri's doctoral thesis, which is available in Munin at http://hdl.handle.net/10037/3555 |
| URI: | http://hdl.handle.net/10037/3052 |
| Abstract: | Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population. Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded. A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium. The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted. |
| URI: | http://hdl.handle.net/10037/3923 |
| Abstract: | Inappropriate medical treatment of co-morbidities in Alzheimer’s disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. Setting: Nine rural municipalities with 70 000 inhabitants in Northern Norway. Participants: Participants with and without AD recruited in general practice and by population based screening. 187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression. A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1 ± 3.6 and 2.9 ± 2.4 respectively, p < 0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9 ± 3.9 and 4.5 ± 3.3, respectively, p < 0.001). AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors. |
| URI: | http://hdl.handle.net/10037/3924 |
| Abstract: | Progressive neurodegeneration in Alzheimer’s disease (AD) induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD. Design: A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added. Setting: Nine rural municipalities in Northern Norway. Participants: 187 participants 65 years and older with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. INTERVENTIONS: In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blindly to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period. Main outcome: Changes in MMSE sum score. Secondary outcome: Changes in ADAS-Cog and Clock Drawing Test. MMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo. In rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results. |
| Description: | This article is part of Fred Andersen's doctoral thesis. Available in Munin at http://hdl.handle.net/10037/3669 |
| URI: | http://hdl.handle.net/10037/4996 |
| Abstract: | The aims of this study were: (1) evaluate enzyme-producing bacteria isolated from the GI tract of Atlantic cod, (2) identify the most promising enzyme-producing bacteria by 16S rRNA gene sequencing and (3) to assess whether these bacteria have the ability to inhibit in vitro growth of four well known pathogenic bacteria; Aeromonas salmonicida subsp. salmonicida, V. (L.) anguillarum, Moritella viscosa and Carnobacterium maltaromaticum. In this study, 79 gut bacteria previously isolated from the GI tract of Atlantic cod fed fish meal (FM), soybean meal (SBM) and bioprocessed soybean meal (BPSBM) from the study of Ringø et al. (2006a), were randomly selected for further investigation. These bacteria had not previously been tested for enzyme-production, identified by 16S rRNA gene sequencing or tested for antagonistic activity. Determination of qualitative enzyme activities; protease, amylase, cellulase, phytase, lipase and chitinase were carried out as described by Ray, Roy, Mondal and Ringø (2010) and Askarian, Zhou, Olsen, Sperstad and Ringø (2011). These endogenous bacterial enzymes were selected as they might contribute to fish nutrition (Ray et al. 2011). Forty eight of the most promising enzyme-producing bacteria, 15, 16 and 17 isolated from the GI tract of Atlantic cod fed FM, SBM and BPSBM, respectively were further identified by 16S rRNA gene sequencing as described by Ringø, Sperstad, Myklebust, Mayhew and Olsen (2006b). All sequences were analysed and edited in BIOEDIT and blasted against the sequences available in GenBank. Gut bacteria showing low similarities (<94%) with known sequences in GenBank were treated as unknown. |
| URI: | http://hdl.handle.net/10037/4353 |
| Abstract: | The present investigation evaluated the effect of chitin (5% supplementation) on the adherent aerobic intestinal microbiota of Atlantic salmon (Salmo salar L.). One hundred and seventy three isolates were isolated but 34 isolates died prior to positive identification. Sixty four out of 139 autochthonous gut bacteria were further identified by 16S rRNA gene sequencing and further tested for protease, amylase, cellulase, phytase, lipase and chitinase activities. Moreover, the most promising enzyme-producing bacteria and intestinal lactic acid bacteria (LAB) were tested for in vitro growth inhibition of four important fish pathogens: Aeromonas salmonicida subsp. salmonicida, Vibrio (Listonella) anguillarum, Moritella viscosa and Carnobacterium maltaromaticum. Dietary chitin modulates the gut microbiota but not the portion of enzyme-producing gut bacteria. LAB were only isolated from fish fed the chitin supplemented diet and they were able to inhibit in vitro growth of 3 of the 4 pathogens. However, the most promising gut bacteria isolated in the present study with respect to enzyme production and in vitro growth inhibition showed high similarity to Bacillus thuringiensis by 16SrRNA gene sequencing. |
| URI: | http://hdl.handle.net/10037/4315 |
| Abstract: | The heterogeneity of cancer cannot always be recognized by tumor morphology, but may be reflected by the underlying genetic aberrations. Array comparative genome hybridization (array-CGH) methods provide high-throughput data on genetic copy numbers, but determining the clinically relevant copy number changes remains a challenge. Conventional classification methods for linking recurrent alterations to clinical outcome ignore sequential correlations in selecting relevant features. Conversely, existing sequence classification methods can only model overall copy number instability, without regard to any particular position in the genome. Here, we present the heterogeneous hidden conditional random field, a new integrated array-CGH analysis method for jointly classifying tumors, inferring copy numbers and identifying clinically relevant positions in recurrent alteration regions. By capturing the sequentiality as well as the locality of changes, our integrated model provides better noise reduction, and achieves more relevant gene retrieval and more accurate classification than existing methods. We provide an efficient L1-regularized discriminative training algorithm, which notably selects a small set of candidate genes most likely to be clinically relevant and driving the recurrent amplicons of importance. Our method thus provides unbiased starting points in deciding which genomic regions and which genes in particular to pursue for further examination. Our experiments on synthetic data and real genomic cancer prediction data show that our method is superior, both in prediction accuracy and relevant feature discovery, to existing methods. We also demonstrate that it can be used to generate novel biological hypotheses for breast cancer. |
| URI: | http://hdl.handle.net/10037/4418 |
| Abstract: | This study investigated the overall clinical impact of anti-α- actinin antibodies in patients with pre-selected autoimmune diseases and in a random group of anti-nuclear antibody (ANA)- positive individuals. The relation of anti-α-actinin antibodies with lupus nephritis and anti-double-stranded DNA (anti-dsDNA) antibodies represented a particular focus for the study. Using a cross-sectional design, the presence of antibodies to α-actinin was studied in selected groups, classified according to the relevant American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) (n = 99), rheumatoid arthritis (RA) (n = 68), Wegener's granulomatosis (WG) (n = 85), and fibromyalgia (FM) (n = 29), and in a random group of ANA-positive individuals (n = 142). Renal disease was defined as (increased) proteinuria with haematuria or presence of cellular casts. Sera from SLE, RA, and Sjøgren's syndrome (SS) patients had significantly higher levels of anti-α-actinin antibodies than the other patient groups. Using the geometric mean (± 2 standard deviations) in FM patients as the upper cutoff, 20% of SLE patients, 12% of RA patients, 4% of SS patients, and none of the WG patients were positive for anti-α- actinin antibodies. Within the SLE cohort, anti-α-actinin antibody levels were higher in patients with renal flares (p = 0.02) and correlated independently with anti-dsDNA antibody levels by enzyme-linked immunosorbent assay (p < 0.007) but not with other disease features. In the random ANA group, 14 individuals had anti-α-actinin antibodies. Of these, 36% had SLE, while 64% suffered from other, mostly autoimmune, disorders. Antibodies binding to α-actinin were detected in 20% of SLE patients but were not specific for SLE. They correlate with anti-dsDNA antibody levels, implying in vitro crossreactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE. |
| URI: | http://hdl.handle.net/10037/1105 |
| Abstract: | Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05–1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m2 increase in body mass index was 1.10 (95% CI, 1.07–1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92–0.99; p = 0.02) in ever-users of hormone therapy. Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. |
| URI: | http://hdl.handle.net/10037/4907 |
| Abstract: | In low-income countries, the use of some organochlorine pesticides is still common in order to increase food production. Monitoring the chemical exposure is an important step in risk-reducing strategies. This is the first study to report concentrations of organochlorines in breast milk of women from Bangladesh where farming is the main income source. Organochlorines such as p,p′-DDT, o,p′-DDT, p,p′-DDE, p,p′-DDD (i.e., ∑DDT), HCB, α-, β- and γ-HCH, trans-chlordane, cis-chlordane, oxy-chlordane, trans-nonachlor, cis-nonachlor, mirex and polychlorinated biphenyls (CB 28, 52, 99, 101, 105, 114, 118, 123, 128, 138, 141, 149, 153, 156, 157, 163, 167, 170, 180, 183, 187, 189, 194) were analyzed in breast milk collected in 2002 from 72 first-time mothers (median age 20 years) living in the rural area Matlab, Bangladesh. While the concentrations of PCBs and many of the pesticides were low, the concentrations of p,p′-DDT and its metabolite p,p′-DDE were high (median 349 and 1645 ng g−1 lipid, respectively) in comparison to other countries. The median value of ∑DDT was 2123 ng g−1 lipid. The estimated daily exposure to p,p′-DDT, p,p′-DDE and ∑DDTs was 10, 30 and 42 μg kg−1 body weight, respectively, in 3 months old infants. The p,p′-DDE/p,p′-DDT ratio ranged from 1 to 23, where 58% of the mothers had a ratio below 5 indicating recent or ongoing DDT exposure. This study reports infant exposure and maternal body burden of organochlorines through breast milk. Although the findings give no reason to limit breast-feeding, it is essential to identify the main exposure sources and find means to decrease the exposure. |
| URI: | http://hdl.handle.net/10037/4977 |
| Abstract: | Chemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators. Tissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin21-157. Biological effects of chemerin21-157 were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants. Both serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin21-157 resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected. These results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin21-157 stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation. |
| URI: | http://hdl.handle.net/10037/4684 |
| Abstract: | Til tross for stadig større inntekter, er mange klubbøkonomier i krise. En viktig årsak til dette er at lønnskostnadene eskalerer. I denne artikkelen drøftes årsaker til lønnspresset i fotballnæringen. Fotballklubber er primært opptatt av sport og ikke av økonomi, men klubbene er avhengige av økonomiske ressurser for å kunne oppnå sportslig suksess. De beste klubbene i Tippeligaen ansetter dyre trenere og spillere for å kunne forfølge sine internasjonale ambisjoner. De dårligste klubbene har på sin side sterke incentiver til å bruke mer penger på lønninger for å kunne opprettholde sine nasjonale ambisjoner. Kostnadene jekkes opp sesong etter sesong siden lønn synes å være det beste virkemidlet mot sportslige utfordringer. Lønnsreduksjoner kan føre til sportslige banesår for en klubb. I denne næringen ser det altså ut som om lønnskostnader er en gordisk knute. |
| URI: | http://hdl.handle.net/10037/3946 |
| Abstract: | MicroRNAs (miRNAs) play a major role in animal ontogenesis. Size variants of miRNAs, isomiRs, are observed along with the main miRNA types, but their origin and possible biological role are uncovered yet. Developmental profiles of miRNAs have been reported in few fish species only and, to our knowledge, differential expressions of isomiRs have not yet been shown during fish development. Atlantic halibut, Hippoglossus hippoglossus L., undergoes dramatic metamorphosis during early development from symmetrical pelagic larval stage to unsymmetrical flatfish. No data exist on role of miRNAs in halibut metamorphosis. miRNA profiling using SOLiD deep sequencing technology revealed a total of 199 conserved, one novel antisense, and one miRNA* mature form. Digital expression profiles of selected miRNAs were validated using reverse transcription quantitative PCR. We found developmental transition-specific miRNA expression. Expression of some miRNA* exceeded the guide strand miRNA. We revealed that nucleotide truncations and/or additions at the 3' end of mature miRNAs resulted in size variants showing differential expression patterns during the development in a number of miRNA families. We confirmed the presence of isomiRs by cloning and Sanger sequencing. Also, we found inverse relationship between expression levels of sense/antisense miRNAs during halibut development. Developmental transitions during early development of Atlantic halibut are associated with expression of certain miRNA types. IsomiRs are abundant and often show differential expression during the development. |
| URI: | http://hdl.handle.net/10037/4410 |
| Abstract: | Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR) and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and marginal zone lymphoma (MZL) patients. Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR), CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p)-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB), p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB) was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation-induced phosphorylation of signaling proteins in distinct cell populations can be used to identify aberrant signaling pathways. |
| URI: | http://hdl.handle.net/10037/4997 |
| Abstract: | Accurate measurement of physical activity (PA) is critical to establish dose-response relationships with various health outcomes. We compared the self-administered PA questionnaire from the Norwegian Women and Cancer Study (NOWAC) with a criterion method in middle-aged Norwegian women. A sample of 177 randomly recruited healthy women attended two clinical visits approximately 4-6 months apart. At each visit, the women completed the NOWAC PA questionnaire (NOPAQ), rating their overall PA level on a 10-category scale (1 being a "very low" and 10 being a "very high" PA level) and performed an 8-minute step-test to estimate aerobic fitness (VO2max). After each visit, the women wore a combined heart rate and movement sensor for 4 consecutive days of free-living. Measures of PA obtained from the combined heart rate and movement sensor, which were used as criterion, included individually calibrated PA energy expenditure (PAEE), acceleration, and hours/day of moderate-to-vigorous intensity PA (MVPA). These were averaged between visits and compared to NOPAQ scores at visit 2. Intra-class correlation coefficients for objective measures from both free-living periods were in the range of 0.65-0.87 (P < 0.001), compared to 0.62 (P < 0.001) for NOPAQ. There was a moderate but significant (P < 0.001) Spearman's rank correlation coefficient in the range of 0.36-0.46 between NOPAQ and objective measures of PA. Linear trends for the association between the NOPAQ rating scale with PAEE, hours/day of MVPA and VO2max (P < 0.001) were also demonstrated. Self-reported PA level measured on a 10-category scale appears valid to rank PA in a female Norwegian population. |
| URI: | http://hdl.handle.net/10037/4429 |
| Abstract: | Physical activity (PA) and its relationship with all-cause mortality suggest a strong and consistent inverse association. This study prospectively investigated the association between PA level and mortality among participants of the Norwegian Women and Cancer (NOWAC) Study. A total of 66,136 NOWAC participants were followed-up until December 31st 2008. PA level and possible confounding factors were obtained through a self-administered questionnaire at enrolment. Cox proportional hazards regression was used to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD) and cancer mortality and PA levels defined from 1 to 10 on a global scale. PA levels 1–4 were associated with a significantly increased risk of all-cause mortality (level 1 RR = 2.35; 95% CI: 1.94–2.84, level 2 RR = 1.71; 95% CI: 1.45–2.00, level 3 RR = 1.30; 95% CI: 1.14–1.49, level 4 RR = 1.07; 95% CI: 0.95–1.22), compared with PA level 5. CVD mortality risk increased in PA levels 1–3 (level 1 RR = 3.50; 95% CI: 2.41–5.10, level 2 RR = 1.50; 95% CI: 0.99–2.25, level 3 RR = 1.12; 95% CI: 0.79–1.60) as did cancer mortality risk (RR = 1.32; 95% CI: 0.96–1.81, RR = 1.48; 95% CI: 1.19–1.84, RR = 1.26; 95% CI: 1.06–1.50, respectively). The magnitude of the associations was consistent across strata of age, smoking, and body mass index. The population attributable fractions for PA levels 1–4 were: all-cause mortality, 11.5%; CVD mortality, 11.3%; cancer mortality, 7.8%. There is a significant trend of increased risk of all-cause, CVD and cancer mortality in relation to low PA levels among Norwegian women. |
| URI: | http://hdl.handle.net/10037/3954 |
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