Health behavior modification after electron beam computed tomography and physician consultation

This study aimed to determine whether participants reported altering health behaviors (physical activity, diet, and alcohol consumption) after seeing results from an electron-beam computed tomography (EBCT) scan for coronary artery calcium and reviewing these results with a physician. Clinicians attempt to motivate patients to control cardiovascular risk factors by adopting healthy behaviors and reducing harmful actions. Asymptomatic patients (N = 510) were evaluated by EBCT for the extent of coronary artery calcium. Information pertaining to demographics, health history, and lifestyle/health behaviors was obtained from each participant at the time of the EBCT scan. Patients were given their numerical calcium score, shown images of their coronary arteries, and counseled by a physician for lifestyle and medical risk modification based on their coronary artery calcium score. Approximately 6 years after the scan, participants completed a follow-up questionnaire related to lifestyle modifications. In multivariable analysis, the presence and extent of coronary artery calcium was significantly associated with beneficial health behavior modifications. Specifically, the greater a patient’s coronary artery calcium score, the more likely they were to report increasing exercise (odds ratio = 1.34, P = 0.02), changing diet (odds ratio = 1.40, P < 0.01), and changing alcohol intake (odds ratio = 1.46, P = 0.05). This study suggests that seeing and being counseled on the presence and extent of coronary artery calcium is significantly associated with behavior change

Advanced Fluorescence Microscopy Techniques-FRAP, FLIP, FLAP, FRET and FLIM

Fluorescence microscopy provides an efficient and unique approach to study fixed and living cells because of its versatility, specificity, and high sensitivity. Fluorescence microscopes can both detect the fluorescence emitted from labeled molecules in biological samples as images or photometric data from which intensities and emission spectra can be deduced. By exploiting the characteristics of fluorescence, various techniques have been developed that enable the visualization and analysis of complex dynamic events in cells, organelles, and sub-organelle components within the biological specimen. The techniques described here are fluorescence recovery after photobleaching (FRAP), the related fluorescence loss in photobleaching (FLIP), fluorescence localization after photobleaching (FLAP), Forster or fluorescence resonance energy transfer (FRET) and the different ways how to measure FRET, such as acceptor bleaching, sensitized emission, polarization anisotropy, and fluorescence lifetime imaging microscopy (FLIM). First, a brief introduction into the mechanisms underlying fluorescence as a physical phenomenon and fluorescence, confocal, and multiphoton microscopy is given. Subsequently, these advanced microscopy techniques are introduced in more detail, with a description of how these techniques are performed, what needs to be considered, and what practical advantages they can bring to cell biological research

Miniature Inverted–Repeat Transposable Elements (MITEs) Have Been Accumulated through Amplification Bursts and Play Important Roles in Gene Expression and Species Diversity in Oryza sativa

Miniature inverted–repeat transposable elements (MITEs) are predicted to play important roles on genome evolution. We developed a BLASTN-based approach for de novo identification of MITEs and systematically analyzed MITEs in rice genome. The genome of rice cultivar Nipponbare (Oryza sativa ssp. japonica) harbors 178,533 MITE-related sequences classified into 338 families. Pairwise nucleotide diversity and phylogenetic tree analysis indicated that individual MITE families were resulted from one or multiple rounds of amplification bursts. The timing of amplification burst varied considerably between different MITE families or subfamilies. MITEs are associated with 23,623 (58.2%) genes in rice genome. At least 7,887 MITEs are transcribed and more than 3,463 were transcribed with rice genes. The MITE sequences transcribed with rice coding genes form 1,130 pairs of potential natural sense/antisense transcripts. MITEs generate 23.5% (183,837 of 781,885) of all small RNAs identified from rice. Some MITE families generated small RNAs mainly from the terminals, while other families generated small RNAs predominantly from the central region. More than half (51.8%) of the MITE-derived small RNAs were generated exclusively by MITEs located away from genes. Genome-wide analysis showed that genes associated with MITEs have significantly lower expression than genes away from MITEs. Approximately 14.8% of loci with full-length MITEs have presence/absence polymorphism between rice cultivars 93-11 (O. sativa ssp. indica) and Nipponbare. Considering that different sets of genes may be regulated by MITE-derived small RNAs in different genotypes, MITEs provide considerable diversity for O. sativa

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure

BACKGROUND: Genotypic antiretroviral resistance testing (GRT) in HIV infection with drug resistant virus is recommended to optimize antiretroviral therapy, in particular in patients with virological failure. We estimated the clinical effect, cost and cost-effectiveness of using GRT as compared to expert opinion in patients with antiretroviral treatment failure. METHODS: We developed a mathematical model of HIV disease to describe disease progression in HIV-infected patients with treatment failure and compared the incremental impact of GRT versus expert opinion to guide antiretroviral therapy. The analysis was conducted from the health care (discount rate 4%) and societal (discount rate 2%) perspective. Outcome measures included life-expectancy, quality-adjusted life-expectancy, health care costs, productivity costs and cost-effectiveness in US Dollars per quality-adjusted life-year (QALY) gained. Clinical and economic data were extracted from the large Swiss HIV Cohort Study and clinical trials. RESULTS: Patients whose treatment was optimized with GRT versus expert opinion had an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and two weeks, respectively. Health care costs with and without GRT were $US 421,000 and$US 419,000, leading to an incremental cost-effectiveness ratio of $US 35,000 per QALY gained. In the analysis from the societal perspective, GRT versus expert opinion led to an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and four weeks, respectively. Health care costs with and without GRT were$US 551,000 and $US 549,000, respectively. When productivity changes were included in the analysis, GRT was cost-saving. CONCLUSIONS: GRT for treatment optimization in HIV-infected patients with treatment failure is a cost-effective use of scarce health care resources and beneficial to the society at large

Risk profiles of prostate cancers identified from UK primary care using national referral guidelines

OBJECTIVE: Prostate cancer in the United Kingdom is mainly diagnosed from primary care referrals based on national guidelines published by the Department of Health. Here we investigated the characteristics of cancers detected through the use of these guidelines. METHODS: A prospective two-centre study was established to assess men referred from the primary care based on the UK national guidelines. RESULTS: The overall cancer detection rate was 43% (169 out of 397) with 15% (26 out of 169) of all cancers metastatic at presentation. Amongst 50-69-year-old men these rates were 34% (68 out of 200) and 15% (10 out of 68). Only 21% (25 out of 123) of men with local cancers had low-risk disease. In comparison to a historical cohort from 2001 (n=137) we found no overall differences in rates of metastatic disease, locally advanced tumours, or risk categories. Amongst 50-69-year-old men with local disease, however, we observed an increase in detection of low-risk cancers in a contemporary cohort (P=0.04). This was primarily because of the increased detection of low-stage organ-confined tumours in this group (P=0.02). CONCLUSION: Use of the UK prostate cancer guidelines detects a high proportion of clinically significant cancers. Use of the guidelines does not seem to have led to an overall change in the clinical characteristics of presenting cancers. There may, however, be a specific benefit in detecting more low-risk disease in younger men

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

False Beliefs About Asylum Seekers to Australia: The Role of Confidence in Such Beliefs, Prejudice, and the Third Person Effect

There has been much controversy about the treatment of asylum seekers in Australia in recent years, with the Australian Government continuing to enforce a very hard-line stance on asylum seekers who arrive to Australia by boat. The present study examined attitudes towards asylum seekers using 164 Australian community members during June 2015 by way of questionnaire. Our primary research question involved how five variables predicted false beliefs about asylum seekers. Specifically, we measured prejudice, the third-person effect, and confidence in the answers given to false beliefs about asylum seekers. Regression results indicated that the main predictors of false beliefs were right-wing political orientation, prejudice, confidence in espousing false beliefs, and the third-person effect (politicians). Furthermore, most of our community participants accepted a large number of false beliefs as being true, with approximately two-thirds of our participants scoring above the midpoint. This reflects similar findings over the last decade or so. Our results indicate that, if one believes in bottom-up change, a more nuanced approach needs to be undertaken with community anti-prejudice interventions

Aldose Reductase Inhibition Prevents Metaplasia of Airway Epithelial Cells

BACKGROUND: Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo. METHODOLOGY/FINDINGS: Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. CONCLUSIONS: The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies