Childhood Inflammatory Bowel Disease in Libya: Epidemiological and Clinical features

Background & Aims: Inflammatory bowel disease is thought to be rare in Libya. The aim is to determine the prevalence of juvenile onset inflammatory bowel disease in Libya. Setting: Al-Fateh childrens' hospital, Benghazi, Libya. Methods: This is a retrospective study of all cases diagnosed over 10 years (1997–2006) with either ulcerative colitis, Crohn's disease or indeterminate colitis. Inclusion criteria were age <15 years at time of presentation who were resident in the eastern part of the country and who diagnosed with inflammatory bowel disease. Clinical features were outlined using a proforma. Results: Sixteen cases were diagnosed with inflammatory bowel disease, of whom 11 were males (M:F ratio of 1.5:1). The prevalence and incidence rates in the year 2006 were 3.6 and 0.9 per 100,000 children, respectively. The incidence rate increased from 0.2 in 2002 to 0.9 in 2006 (Z score of 39.87, p= 0.00). The age at presentation ranged from 5 months to 14 years. Nine had Crohn's disease (6 males) and 6 had ulcerative colitis (4 males). One patient had indeterminate colitis. The most common clinical features were diarrhea in 10 (62.5%), abdominal pain, anorexia and weight loss in 9 (56.2%), anemia in 7 (43.75%) and vomiting in 6 (37%). Ileopancolitis was found in 3 patients whereas 6 patients had ileocecal disease. Conclusions: Childhood inflammatory bowel disease in this population is not so rare and it is increasing. The clinical pattern is similar to that reported by others

Screening for eukaryotic signal transduction and Mycobacterium isocitrate lyase inhibitor from actinomycetes and fungi of dipterocarp rain forests at Imabak Valey, Sabah, Malaysia

A diversity of actinomycetes and fungi was isolated from various sites during the Imbak Valley Scientific Expedition 2000. A total of 144 soil samples were collected under trees that have been identified to species or genus level. Imbak Valley is a lowland dipterocarp forest, which is interestingly dominated by Dryobalanops beccarii. Isolation of Streptomyces and non-Streptomyces actinomycetes on HV medium and other specific isolation media for non-Streptomyces yielded 203 isolates from 89 soil samples. Morphological characterisation of the isolated actinomycetes was carried out based on aerial mycelium colour, substrate mycelium colour and diffusible pigment production on oatmeal medium. Nine strains of fungi were isolated from the six soil samples plated on PDA medium. All actinomycetes isolates were grown under aerobic condition in liquid culture and extracted with acetone, and used for screening against proteins involved eukaryotic signal transduction. Yeast MAPK kinase and MAP kinase phosphatase were some of the targeted proteins used in this research. MKK1P386 and MKK1P386-MSG5 mutant yeasts were used to screen for these inhibitors, as these yeast kinase and phosphatase have homologous proteins in the MAP kinase signal transduction pathway in human. No inhibitors in the extracts were found in these screenings. Type 1 protein serine/ threonine phosphatase (GLC7) in yeast was used to screen inhibitors against PP1 inhibitors and no inhibitor was found. None of the fungal extracts showed any inhibitory activities in all the screening systems. No Ras/Raf inhibitor was found in the in vivo Ras/Raf interaction with the yeast two-hybrid screening system, which used to screen for inhibitor against Ras/ Raf protein interaction inhibitor. There were 11 actinomycetes extracts that showed toxicity against yeast strain LZ (transformant of Ras/ Raf). H7667, a Streptomycete toxic to yeast is further screened for inhibitors of the GSK3-beta pathway. H7763, a Streptomyces species that showed positive in the primary screen for inhibitor of isocitrate lyase (ICL) which is not itaconic acid (known ICL inhibitor). H7240 showed the strongest susceptibility towards the resin in which the concentration of 5g/l of resin is sufficient to produce growth inhibition of the bacteria

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Glutamate-Gated Chloride Channels of Haemonchus contortus Restore Drug Sensitivity to Ivermectin Resistant Caenorhabditis elegans

Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl) gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits from C. elegans and H. contortus in a highly resistant triple mutant C. elegans strain (DA1316) under the control of the avr-14 promoter; expression of GFP behind this promoter recapitulated the pattern previously reported for avr-14. Expression of ivermectin-sensitive subunits from both species restored drug sensitivity to transgenic worms, though some quantitative differences were noted between lines. Expression of an ivermectin-insensitive subunit, Hco-GLC-2, had no effect on drug sensitivity. Expression of a previously uncharacterised parasite-specific subunit, Hco-GLC-6, caused the transgenic worms to become ivermectin sensitive, suggesting that this subunit also encodes a GluCl that responds to the drug. These results demonstrate that both orthologous and paralogous subunits from C. elegans and H. contortus are able to rescue the ivermectin sensitivity of mutant C. elegans, though some quantitative differences were observed between transgenic lines in some assays. C. elegans is a suitable system for studying parasitic nematode genes that may be involved in drug resistance

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved