Four genomic islands that mark post-1995 pandemic Vibrio parahaemolyticus isolates

BACKGROUND: Vibrio parahaemolyticus is an aquatic, halophilic, Gram-negative bacterium, first discovered in 1950 in Japan during a food-poisoning outbreak. Infections resulting from consumption of V. parahaemolyticus have increased globally in the last 10 years leading to the bacterium's classification as a newly emerging pathogen. In 1996 the first appearance of a pandemic V. parahaemolyticus clone occurred, a new O3:K6 serotype strain that has now been identified worldwide as a major cause of seafood-borne gastroenteritis. RESULTS: We examined the sequenced genome of V. parahaemolyticus RIMD2210633, an O3:K6 serotype strain isolated in Japan in 1996, by bioinformatic analyses to uncover genomic islands (GIs) that may play a role in the emergence and pathogenesis of pandemic strains. We identified 7 regions ranging in size from 10 kb to 81 kb that had the characteristics of GIs such as aberrant base composition compared to the core genome, presence of phage-like integrases, flanked by direct repeats and the absence of these regions from closely related species. Molecular analysis of worldwide clinical isolates of V. parahaemolyticus recovered over the last 33 years demonstrated that a 24 kb region named V. parahaemolyticus island-1 (VPaI-1) encompassing ORFs VP0380 to VP0403 is only present in new O3:K6 and related strains recovered after 1995. We investigated the presence of 3 additional regions, VPaI-4 (VP2131 to VP2144), VPaI-5 (VP2900 to VP2910) and VPaI-6 (VPA1254 to VPA1270) by PCR assays and Southern blot analyses among the same set of V. parahaemolyticus isolates. These 3 VPaI regions also gave similar distribution patterns amongst the 41 strains examined. CONCLUSION: The 4 VPaI regions examined may represent DNA acquired by the pandemic group of V. parahaemolyticus isolates that increased their fitness either in the aquatic environment or in their ability to infect humans

Women Have Higher Protein Content of β-Oxidation Enzymes in Skeletal Muscle than Men

It is well recognized that compared with men, women have better ultra-endurance capacity, oxidize more fat during endurance exercise, and are more resistant to fat oxidation defects i.e. diet-induced insulin resistance. Several groups have shown that the mRNA and protein transcribed and translated from genes related to transport of fatty acids into the muscle are greater in women than men; however, the mechanism(s) for the observed sex differences in fat oxidation remains to be determined. Muscle biopsies from the vastus lateralis were obtained from moderately active men (N = 12) and women (N = 11) at rest to examine mRNA and protein content of genes involved in lipid oxidation. Our results show that women have significantly higher protein content for tri-functional protein alpha (TFPα), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) (P<0.05). There was no significant sex difference in the expression of short-chain hydroxyacyl-CoA dehydrogenase (SCHAD), or peroxisome proliferator activated receptor alpha (PPARα), or PPARγ, genes potentially involved in the transcriptional regulation of lipid metabolism. In conclusion, women have more protein content of the major enzymes involved in long and medium chain fatty acid oxidation which could account for the observed differences in fat oxidation during exercise

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

A Baiting System For Delivery Of An Oral Plague Vaccine To Black-Tailed Prairie Dogs

Laboratory and field studies were conducted between July and October 1999 to identify bait preference, biomarker efficacy, and bait acceptance rates for delivering an oral plague vaccine to black-tailed prairie dogs (Cynomys ludovicianus). Twenty juvenile captive prairie dogs were offered alfalfa baits containing either alfalfa, alfalfa and 5% molasses, or alfalfa, 5% molasses and 4% salt. Based on the results of these trials we selected a bait containing alfalfa, 7% molasses, and 1% salt for field trials to determine bait acceptance rates by free-ranging animals. The biomarkers DuPont Blue dye, iophenoxic acid, and tetracycline hydrochloride were orally administered to captive prairie dogs to determine their efficacy. Only tetracycline proved effective as a biomarker. Two field trials were conducted at separate prairie dog colonies located at the Buffalo Gap National Grassland (Pennington County, South Dakota, USA). In Trial 1, three baits containing tetracycline were distributed around each active burrow entrance and an additional bait was placed inside the burrow (1,276 baits total). In Trial 2, baits were distributed at the same density per burrow as Trial 1, but along transects spaced 10 m apart (1,744 baits total). Trapping began 3 days after bait distribution, and 30 prairie dogs then were captured at each site to determine the percentage of animals marked. In Trial 1, 67% of the prairie dogs captured had tetracycline deposits indicative of bait consumption. In Trial 2, 83% of the prairie dogs had ingested a bait. Approximately 15% of the animals in both trials ate more than one bait. Fleas (Opisocrostis hirsutus) were found on 64 of 70 (91%) of the prairie dogs captured during this study

Evaluation of Different Rice Baits and Chemicals to Improve Efficacy of 2% DRC-1339 to Reduce Blackbird Damage to Rice

Blackbird damage to sprouting rice can be locally severe and costs Louisiana growers an estimated $4 million/year and Texas growers$4.4 million/year. DRC-1339 blackbird baiting programs probably will continue until available alternative control techniques (i.e., repellents) become available. We conducted 3 studies to evaluate different rice baits and chemicals to improve efficacy of DRC-1339 for use at staging areas. During the first study, individually caged red-winged blackbirds preferred untreated medium grain brown rice over long grain brown rice, rough rice, or rough rice soaked with sodium bisulfite. Of birds offered only medium (control), long, rough, and rough rice soaked with sodium bisulfite treated with 2% DRC-1339 diluted 1:25 with untreated carrier (medium, long, or rough rice), 90 to 100% died within 48 hrs. During the second study, individually caged red-winged blackbirds preferred untreated rice over rice treated with Harvest Guard or ethyl cellulose. Birds were offered only medium brown rice (control), Harvest Guard, or ethyl cellulose-treated medium brown rice treated with 2% DRC-1339 diluted 1 :25 with untreated medium grain brown rice. With the medium grain brown rice (field bait), 100% mortality was observed within 48 hrs. With the Harvest Guard and ethyl cellulose treatments, 580% mortality was observed. The third study was an aviary test to determine if aging the chemical baits (sodium bisulfite, Harvest Guard, ethyl cellulose) for 3 days in Louisiana would affect mortality. Mortality with the fresh field and sodium bisulfite baits were 100%. We did not achieve 280% mortality with either the fresh Harvest Guard or ethyl cellulose bait. Mortality with the aged sodium bisulfite bait was 50%. None of the other aged baits produced \u3el0% mortality. Degradation occurred with all the aged baits but occurred the least with the sodium bisulfite treatment. Future research will look at possibly combining sodium bisulfite with W protection to further reduce the degradation of DRC-1339 in the field

The Freedom Forum: From Rosslyn to Timbuktu to Pennsylvania Avenue

Video from September 14, 2011. From Rosslyn to Timbuktu to Pennsylvania Avenue – panel discussion with Chris Wells, Pam Galloway-Tabb, Jerry Sass, Jack Hurley and Rod Sandeen