339 research outputs found

    On fractionality of the path packing problem

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    In this paper, we study fractional multiflows in undirected graphs. A fractional multiflow in a graph G with a node subset T, called terminals, is a collection of weighted paths with ends in T such that the total weights of paths traversing each edge does not exceed 1. Well-known fractional path packing problem consists of maximizing the total weight of paths with ends in a subset S of TxT over all fractional multiflows. Together, G,T and S form a network. A network is an Eulerian network if all nodes in N\T have even degrees. A term "fractionality" was defined for the fractional path packing problem by A. Karzanov as the smallest natural number D so that there exists a solution to the problem that becomes integer-valued when multiplied by D. A. Karzanov has defined the class of Eulerian networks in terms of T and S, outside which D is infinite and proved that whithin this class D can be 1,2 or 4. He conjectured that D should be 1 or 2 for this class of networks. In this paper we prove this conjecture.Comment: 18 pages, 5 figures in .eps format, 2 latex files, main file is kc13.tex Resubmission due to incorrectly specified CS type of the article; no changes to the context have been mad

    Regulation of neutrophil senescence by microRNAs

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    Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

    A cross-sectional study of patients with and without substance use disorders in Community Mental Health Centres

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    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies have consistently established high comorbidity between psychiatric disorders and substance use disorders (SUD). This comorbidity is even more prominent when psychiatric populations are studied. Previous studies have focused on inpatient populations dominated by psychotic disorders, whereas this paper presents findings on patients in Community Mental Health Centres (CMHCs) where affective and anxiety disorders are most prominent. The purpose of this study is to compare patients in CMHCs with and without SUD in regard to differences in socio-demographic characteristics, level of morbidity, prevalence of different diagnostic categories, health services provided and the level of improvement in psychiatric symptoms.</p> <p>Methods</p> <p>As part of the evaluation of the National Plan for Mental Health, all patients seen in eight CMHCs during a 4-week period in 2007 were studied (n = 2154). The CMHCs were located in rural and urban areas of Norway. The patients were diagnosed according to the ICD-10 diagnoses and assessed with the Health of the Nation Outcome Scales, the Alcohol Use Scale and the Drug Use Scale.</p> <p>Results</p> <p>Patients with SUD in CMHCs are more frequently male, single and living alone, have more severe morbidity, less anxiety and mood disorders, less outpatient treatment and less improvement in regard to recovery from psychological symptoms compared to patients with no SUD.</p> <p>Conclusion</p> <p>CMHCs need to implement systematic screening and diagnostic procedures in order to detect the special needs of these patients and improve their treatment.</p

    Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study

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    <p>Abstract</p> <p>Background</p> <p>Consumption of cured/smoked meat and fish leads to the formation of carcinogenic <it>N-</it>nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia.</p> <p>Methods</p> <p>A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses.</p> <p>Results</p> <p>Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83) and bean-curd (OR = 0.55; 95% CI: 0.34–0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea.</p> <p>Conclusion</p> <p>Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.</p

    Severity of Depression, Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort.

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    Background: Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association. Methods: We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases. Findings: Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD. Conclusion: This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress

    Efficacy of a meal replacement diet plan compared to a food-based diet plan after a period of weight loss and weight maintenance: a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Obesity has reached epidemic proportions in the United States. It is implicated in the development of a variety of chronic disease states and is associated with increased levels of inflammation and oxidative stress. The objective of this study is to examine the effect of Medifast's meal replacement program (MD) on body weight, body composition, and biomarkers of inflammation and oxidative stress among obese individuals following a period of weight loss and weight maintenance compared to a an isocaloric, food-based diet (FB).</p> <p>Methods</p> <p>This 40-week randomized, controlled clinical trial included 90 obese adults with a body mass index (BMI) between 30 and 50 kg/m<sup>2</sup>, randomly assigned to one of two weight loss programs for 16 weeks and then followed for a 24-week period of weight maintenance. The dietary interventions consisted of Medifast's meal replacement program for weight loss and weight maintenance, or a self-selected, isocaloric, food-based meal plan.</p> <p>Results</p> <p>Weight loss at 16 weeks was significantly better in the Medifast group (MD) versus the food-based group (FB) (12.3% vs. 6.9%), and while significantly more weight was regained during weight maintenance on MD versus FB, overall greater weight loss was achieved on MD versus FB. Significantly more of the MD participants lost ≥ 5% of their initial weight at week 16 (93% vs. 55%) and week 40 (62% vs. 30%). There was no difference in satiety observed between the two groups during the weight loss phase. Significant improvements in body composition were also observed in MD participants compared to FB at week 16 and week 40. At week 40, both groups experienced improvements in biochemical outcomes and other clinical indicators.</p> <p>Conclusions</p> <p>Our data suggest that the meal replacement diet plan evaluated was an effective strategy for producing robust initial weight loss and for achieving improvements in a number of health-related parameters during weight maintenance, including inflammation and oxidative stress, two key factors more recently shown to underlie our most common chronic diseases.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT01011491</p

    Factors Influencing Engagement, Perceived Usefulness and Behavioral Mechanisms Associated with a Text Message Support Program

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    Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours. We aimed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement, perceived usefulness, behavior change and program delivery preferences. Methods Mixed methods qualitative design combining four data sources; (i) analytic data extracted directly from the software system, (ii) participant survey, (iii) focus groups to identify barriers and enablers to implementation and mechanisms of effect and (iv) recruitment screening logs and text message responses to examine engagement. This evaluation was conducted within the TEXT ME trial—a parallel design, single-blind randomized controlled trial (RCT) of 710 patients with coronary heart disease (CHD). Qualitative data were interpreted using inductive thematic analysis. Results 307/352 (87% response rate) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group. Factors increasing engagement included (i) ability to save and share messages, (ii) having the support of providers and family, (iii) a feeling of support through participation in the program, (iv) the program being initiated close to the time of a cardiovascular event, (v) personalization of the messages, (vi) opportunity for initial face-to-face contact with a provider and (vii) that program and content was perceived to be from a credible source. Clear themes relating to program delivery were that diet and physical activity messages were most valued, four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer. Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aimed at improving health-related behavior. The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling

    Activating Transcription Factor 4 Confers a Multidrug Resistance Phenotype to Gastric Cancer Cells through Transactivation of SIRT1 Expression

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    BACKGROUND: Multidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression confered the MDR phenotype to gastric cancer cells, while knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we also showed that the NAD(+)-dependent histone deacetylase SIRT1 was required for ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4 facilitated MDR in gastric cancer cells through direct binding to the SIRT1 promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by small interfering RNA (siRNA) or a specific inhibitor (EX-527) reintroduced therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells in response to chemotherapy and these findings suggest that targeting ATF4 could relieve therapeutic resistance in gastric cancer
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