San Francisco Hep B Free: A Grassroots Community Coalition to Prevent Hepatitis B and Liver Cancer

Chronic hepatitis B is the leading cause of liver cancer and the largest health disparity between Asian/Pacific Islanders (APIs) and the general US population. The Hep B Free model was launched to eliminate hepatitis B infection by increasing hepatitis B awareness, testing, vaccination, and treatment among APIs by building a broad, community-wide coalition. The San Francisco Hep B Free campaign is a diverse public/private collaboration unifying the API community, health care system, policy makers, businesses, and the general public in San Francisco, California. Mass-media and grassroots messaging raised citywide awareness of hepatitis B and promoted use of the existing health care system for hepatitis B screening and follow-up. Coalition partners reported semi-annually on activities, resources utilized, and system changes instituted. From 2007 to 2009, over 150 organizations contributed approximately $1,000,000 in resources to the San Francisco Hep B Free campaign. 40 educational events reached 1,100 healthcare providers, and 50% of primary care physicians pledged to screen APIs routinely for hepatitis B. Community events and fairs reached over 200,000 members of the general public. Of 3,315 API clients tested at stand-alone screening sites created by the campaign, 6.5% were found to be chronically infected and referred to follow-up care. A grassroots coalition that develops strong partnerships with diverse organizations can use existing resources to successfully increase public and healthcare provider awareness about hepatitis B among APIs, promote routine hepatitis B testing and vaccination as part of standard primary care, and ensure access to treatment for chronically infected individuals

Four plant defensins from an indigenous South African Brassicaceae species display divergent activities against two test pathogens despite high sequence similarity in the encoding genes

<p>Abstract</p> <p>Background</p> <p>Plant defensins are an important component of the innate defence system of plants where they form protective antimicrobial barriers between tissue types of plant organs as well as around seeds. These peptides also have other activities that are important for agricultural applications as well as the medical sector. Amongst the numerous plant peptides isolated from a variety of plant species, a significant number of promising defensins have been isolated from Brassicaceae species. Here we report on the isolation and characterization of four defensins from <it>Heliophila coronopifolia</it>, a native South African Brassicaceae species.</p> <p>Results</p> <p>Four defensin genes (<it>Hc-AFP1</it>-<it>4) </it>were isolated with a homology based PCR strategy. Analysis of the deduced amino acid sequences showed that the peptides were 72% similar and grouped closest to defensins isolated from other Brassicaceae species. The Hc-AFP1 and 3 peptides shared high homology (94%) and formed a unique grouping in the Brassicaceae defensins, whereas Hc-AFP2 and 4 formed a second homology grouping with defensins from <it>Arabidopsis </it>and <it>Raphanus</it>. Homology modelling showed that the few amino acids that differed between the four peptides had an effect on the surface properties of the defensins, specifically in the alpha-helix and the loop connecting the second and third beta-strands. These areas are implicated in determining differential activities of defensins. Comparing the activities after recombinant production of the peptides, Hc-AFP2 and 4 had IC₅₀values of 5-20 μg ml^-1against two test pathogens, whereas Hc-AFP1 and 3 were less active. The activity against <it>Botrytis cinerea </it>was associated with membrane permeabilization, hyper-branching, biomass reduction and even lytic activity. In contrast, only Hc-AFP2 and 4 caused membrane permeabilization and severe hyper-branching against the wilting pathogen <it>Fusarium solani</it>, while Hc-AFP1 and 3 had a mild morphogenetic effect on the fungus, without any indication of membrane activity. The peptides have a tissue-specific expression pattern since differential gene expression was observed in the native host. <it>Hc-AFP1 </it>and <it>3 </it>expressed in mature leaves, stems and flowers, whereas <it>Hc-AFP2 </it>and <it>4 </it>exclusively expressed in seedpods and seeds.</p> <p>Conclusions</p> <p>Two novel Brassicaceae defensin sequences were isolated amongst a group of four defensin encoding genes from the indigenous South African plant <it>H. coronopifolia</it>. All four peptides were active against two test pathogens, but displayed differential activities and modes of action. The expression patterns of the peptide encoding genes suggest a role in protecting either vegetative or reproductive structures in the native host against pathogen attack, or roles in unknown developmental and physiological processes in these tissues, as was shown with other defensins.</p

The kinetic properties of various R258 mutants of deacetoxycephalosporin C synthase.

Site-directed mutagenesis was used to investigate the control of 2-oxoacid cosubstrate selectivity by deacetoxycephalosporin C synthase. The wild-type enzyme has a requirement for 2-oxoglutarate and cannot efficiently use hydrophobic 2-oxoacids (e.g. 2-oxohexanoic acid, 2-oxo-4-methyl-pentanoic acid) as the cosubstrate. The following mutant enzymes were produced: R258A, R258L, R258F, R258H and R258K. All of the mutants have broadened cosubstrate selectivity and were able to utilize hydrophobic 2-oxoacids. The efficiency of 2-oxoglutarate utilization by all mutants was decreased as compared to the wild-type enzyme, and in some cases activity was abolished with the natural cosubstrate

PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma

Background Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents. Methods We have studied the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2). Results 15-deoxy-prostaglandin J2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis. Conclusion Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent

Knowledge, attitudes and practices among people with chronic hepatitis B attending a hepatology clinic in Malaysia: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>Hepatitis B (HBV) is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. This study assessed the knowledge, attitudes and practices of people with chronic HBV and the associated factors.</p> <p>Methods</p> <p>This cross-sectional study was conducted at an outpatient adult hepatology clinic at a tertiary hospital in Kuala Lumpur. A self-administered questionnaire was administered on a one-to-one basis to assess knowledge, attitudes, and lifestyle practices of people with chronic HBV.</p> <p>Results</p> <p>The response rate was 89% (n = 483/543). Participants had a mean age of 46.3 (±14.7) years and the mean duration of HBV from time of diagnosis was 12.2 (±8.8) years. The mean knowledge score was 12.57/20 (standard deviation: ±4.4, range: 0–19). Participants aged 30–39 years, with higher educational attainment, employed in professional jobs, longer duration of diagnosis and those without cirrhosis had significantly higher knowledge scores. Age, education level and duration of diagnosis were significant predictors of the knowledge score on standard multiple regression analysis. More than half of the participants were worried of spreading HBV infection to family and friends and worried since the diagnosis. A third of the participants (33.5%) were embarrassed to reveal their diagnosis to the public but most of them (93.6%) would inform their family. Those who reported feeling worried since their diagnosis were more likely to be middle-aged, of Malay ethnicity, have shorter duration of diagnosis of less than 10 years and have received therapy. About half of the participants (50.6%) did not share dining utensils and the majority (93.2%) believed that HBV can be transmitted by sharing of eating and drinking utensils. Older patients were significantly less likely to share utensils. Those who felt worried since diagnosis had significant higher knowledge of HBV.</p> <p>Conclusion</p> <p>The findings highlight the stigma and misconceptions that still exist among the HBV patients. More patient and public education about HBV and its prevention are essential to increase awareness and to demystify the disease.</p