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Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

We present experimental γ-ray strength functions up to Eγ ∼ Sn measured at the Oslo Cyclotron Laboratory for several Sc, V, Mo, and Sn isotopes. For the lighter nuclei, an unexpected enhancement of the strength function at low γ-ray energies has been revealed. This enhancement could potentially have an impact on neutron-capture cross sections for unstable, neutron-rich nuclei. For the Sn isotopes, we observe increased strength around the neutron separation energy Sn.

We present preliminary results from a measurement of nuclear level densities and the γ-ray strength of light Sc and Ti isotopes using the Oslo Method.

Abstract Background In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship. Methods A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken. Results There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol. Conclusion The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.

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Abstract Background It has long been evident that there is an association between alcohol use and risk of tuberculosis. It has not been established to what extent this association is confounded by social and other factors related to alcohol use. Nor has the strength of the association been established. The objective of this study was to systematically review the available evidence on the association between alcohol use and the risk of tuberculosis. Methods Based on a systematic literature review, we identified 3 cohort and 18 case control studies. These were further categorized according to definition of exposure, type of tuberculosis used as study outcome, and confounders controlled for. Pooled effect sizes were obtained for each sub-category of studies. Results The pooled relative risk across all studies that used an exposure cut-off level set at 40 g alcohol per day or above, or defined exposure as a clinical diagnosis of an alcohol use disorder, was 3.50 (95% CI: 2.01–5.93). After exclusion of small studies, because of suspected publication bias, the pooled relative risk was 2.94 (95% CI: 1.89–4.59). Subgroup analyses of studies that had controlled for various sets of confounders did not give significantly different results and did not explain the significant heterogeneity that was found across the studies. Conclusion The risk of active tuberculosis is substantially elevated in people who drink more than 40 g alcohol per day, and/or have an alcohol use disorder. This may be due to both increased risk of infection related to specific social mixing patterns associated with alcohol use, as well as influence on the immune system of alcohol itself and of alcohol related conditions.

Graphical abstract Highlights • Extensive malting of wheat induces resistance to intestinal secretion and diarrhoea. • The substances in malt causing >50% inhibition of secretion are 2-methyl-catechols. • The 2-methyl-catechols seems to act via the vanilloid receptor TRPV1. • The resistance is mediated by antisecretory factor in blood, probably via TRPV1. Abstract Antisecretory factor (AF) is a protein which regulates fluid transport in the intestine and other organs. Extensive malting of wheat releases certain chemicals which induce AF and inhibit enterotoxic diarrhoea. The aim of this study was to identify AF-inducing substances in wheat malt. The active fractions of the malt leachate contained guaiacol, ferulic acid, and vanillic acid. These three 2-methyl-catechols gave >50% inhibition of cholera toxin-induced secretion in the gut. In contrast, fully methylated catechol had the opposite action; that is, they were secretory rather than antisecretory. Guaiacol and ferulic acid were further shown to induce AF in blood. Since the 2-methoxyphenol structure is present in substances binding to the vanilloid receptor, TRPV1, the specific blocker of this receptor—capsazepine—was tested. This substance exerted >50% inhibition of cholera secretion. Thus 2-methyl-catechols in wheat malt induce AF, and probably exert their effect via the TRPV1 receptor. [ABSTRACT FROM AUTHOR]

Binding, degradation, and antilipolytic effect of insulin were studied during the differentiation of preadipocytes into unilocular adipocytes. The precursor cells were isolated from the stromal-vascular fraction of adult rat epididymal fat pads and were cultured according to methods previously described. Under appropriate conditions the cells attained full morphological maturation after 6 days. A gradual increase in insulin binding was found concomitant with the morphological development of the preadipocytes into adipocytes. This increase was due to an enhanced number of binding sites whether expressed per cell or per unit cell surface area. The presence of a high insulin concentration (1.67 micrograms/ml or 278 nM) in the culture medium did not prevent this effect. The receptor density, expressed per unit surface area, was higher in the newly developed univacuolar cells than in mature fat cells from the same rat. The increased receptor density was also reflected by a leftward shift in the dose-response curve for the antilipolytic effect of insulin. In parallel with the increased binding, insulin degradation also increased. The lipolytic response to catecholamine also showed a gradual increase with development. When expressed per unit surface area, newly formed cells exhibited a considerably greater response (approximately 3.4 times) than mature cells from the same animals. The maximal antilipolytic effect of insulin in new cells was of the same order as in old cells when the data were expressed per unit cell surface area. Thus, the data show that developing adipocyte precursors gain membrane properties similar to those of mature fat cells. This cell system may serve as a useful model for studying receptor formation and factors that regulate hormone responsiveness.

OBJECTIVE: To compare processes and outcomes of four public-private mix (PPM) projects on DOTS implementation for tuberculosis (TB) control in New Delhi, India; Ho Chi Minh City, Viet Nam; Nairobi, Kenya; and Pune, India. METHODS: Cross-project analysis of secondary data from separate project evaluations was used. Differences among PPM project sites in impact on TB control (change in case detection, treatment outcomes and equity in access) were correlated with differences in chosen intervention strategies and structural conditions. FINDINGS: The analysis suggests that an effective intervention package should include the following provider-side components: (1) orienting private providers (PPs) and the staff of the national TB programme (NTP); (2) improving the referral and information system through simple practical tools; (3) the NTP adequately supervising and monitoring PPs; and (4) the NTP providing free anti-TB drugs to patients treated in the private sector. CONCLUSION: Getting such an intervention package to work requires that the NTP be strongly committed to supporting, supervising and evaluating PPM projects. Further, using a local nongovernmental organization or a medical association as an intermediary may facilitate collaboration. Investing time and effort to ensure that sufficient dialogue takes place among all stakeholders is important to help build trust and achieve a high level of agreement.

Background: Mental health disorders, social stress, and poor health-related quality of life are commonly reported among people with tuberculosis (TB). We conducted a systematic review and meta-analysis to quantify mental health disorders, social stressors, and health-related quality of life in patients with multidrug-resistant tuberculosis (MDR-TB).Methods: We searched PubMed, SCOPUS, ProQuest, Web of Science, and PsycINFO databases for studies that reported data on mental health disorders, social stressors, and health-related quality of life among MDR-TB patients. Hand-searching the reference lists of included studies was also performed. Studies were selected according to pre-defined selection criteria and data were extracted by two authors. Pooled prevalence and weighted mean difference estimates were performed using random-effects meta-analysis. Heterogeneity was explored using meta-regression, and subgroup analyses were performed.Results: We included a total of 40 studies that were conducted in 20 countries. Depression, anxiety, and psychosis were the most common mental health disorders reported in the studies. The overall pooled prevalence was 25% (95% confidence interval (CI): 14, 39) for depression, 24% (95% CI: 2, 57) for anxiety, and 10% (95% CI: 7, 14) for psychosis. There was substantial heterogeneity in the estimates. The stratified analysis showed that the prevalence of psychosis was 4% (95% CI: 0, 22) before MDR-TB treatment commencement, and 9% (95% CI: 5, 13) after MDR-TB treatment commencement. The most common social stressors reported were stigma, discrimination, isolation, and a lack of social support. Health-related quality of life was significantly lower among MDR-TB patients when compared to drug-susceptible TB patients (Q = 9.88, p = 0.01, I2 = 80%).Conclusions: This review found that mental health and social functioning are compromised in a significant proportion of MDR-TB patients, a finding confirmed by the poor health-related quality of life reported. Thus, there is a substantial need for integrating mental health services, social protection and social support into the clinical and programmatic management of MDR-TB. [ABSTRACT FROM AUTHOR]