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PubMed1992

The colorectal cancer gene hunt: current findings.

Identification of four genes, each with its own clinical significance, promises probes for early diagnosis of colorectal cancer in the near future. It also suggests possibilities for new forms of chemotherapy to offset the effects of mutated or lost genes. Given the "moving target" of metastasis, this is likely to be a more fruitful approach than gene replacement--and a more immediate one.

Adenomatous Polyposis Coli↗
PubMed2005

Look what I found! Poison hunting on eBay.

BACKGROUND: Many substances deemed too dangerous for commercial use are still available to the general public. The purchase of these substances may potentially place members of the general public at risk for serious poisonings. This study was designed to document the large variety of dangerous poisons readily available on a popular online auction Web site. Methods. Over a 10-month period, the online auction Web site eBays was searched daily using the terms "poison" and "contents." Product name, active ingredients, what form the product is in, amount in container, and relative toxicity rating (Clinical Toxicology of Commercial Products, Gosselin, et al.) were recorded. If available, pictures of the products were saved. RESULTS: One hundred twenty-one individual products were identified. Fifty-five were in solid/tablet form, 37 were powders, and 29 were liquids. Product containers were full for 56 items and partially full for 65. Twenty-four products contained ingredients rated as "supertoxic" and included strychnine (10), arsenic trioxide (8), cyanide (2) and nicotine, pilocarpine, phosphorus, powdered conium maculatum (1 each). Sixty-three products contained "extremely toxic" ingredients including thallium, picrotoxin, soluble barium, antimony, mercury, arsenates, podophyllin, fluoride, zinc phosphide, atropine, scopolamine, and plant extracts of gelsemium, aconite, larkspur, and croton. Twenty-one products contained "very toxic" ingredients including lead, copper, camphor, caffeine, theobromine, creosote, pyrogallic acid, sparteine, quinine, lindane, warfarin, phenol, and digitalis. The remaining 13 were "moderately-slightly toxic." CONCLUSION: While the viability of the labeled ingredients could not be verified, the transportation, handling, and potential utilization of these dangerous poisons by the general public could result in serious poisonings.

Agrochemicals↗
PubMed2006

The hunt for HIV-1 integrase inhibitors.

Currently, there are three distinct mechanistic classes of antiretrovirals: inhibitors of the HIV- 1 reverse transcriptase and protease enzymes and inhibitors of HIV entry, including receptor and coreceptor binding and cell fusion. A new drug class that inhibits the HIV-1 integrase enzyme (IN) is in development and may soon be available in the clinic. IN is an attractive drug target because it is essential for a stable and productive HIV-1 infection and there is no mammalian homologue of IN. Inhibitors of integrase enzyme (INI) block the integration of viral double-stranded DNA into the host cell's chromosomal DNA. HIV-1 integration has many potential steps that can be inhibited and several new compounds that target specific integration steps have been identified by drug developers. Recently, two INIs, GS-9137 and MK-0518, demonstrated promising early clinical trial results and have been advanced into later stage trials. In this review, we describe how IN facilitates HIV-1 integration, the needed enzyme cofactors, and the resultant byproducts created during integration. Furthermore, we review the different INIs under development, their mechanism of actions, site of IN inhibition, potency, resistance patterns, and discuss the early clinical trial results.

Drug Design↗
PubMed1996

Hunting for trees in binary character sets: efficient algorithms for extraction, enumeration, and optimization.

We describe a useful and efficient tree building technique that is closely related to the maximum compatible subset method. Given a set of binary characters C and a degree bound d, the algorithm we describe counts the number of trees T that satisfy (1) the edges of T correspond to characters contained in C, and (2) the vertices of T have degree bounded by d. If the characters are weighted then we can efficiently determine which of these trees have maximum summed edge weight, where the weight of an edge equals the weight of the corresponding binary character in C. The complexity of the algorithms equals O(nk + ndK(d-1), where n is the number of taxa, k is the number of characters, and K is the number of distinct characters. A number of new tree consensus methods based on the algorithm are introduced, including one that uses edge weighted trees. As well, we illustrate the applicability of the algorithm for large sequence data sets by analyzing sequences from the "Out of Africa" mtDNA data set.

Algorithms↗
PubMed2006

The long-term effect of insomnia on work disability: the HUNT-2 historical cohort study.

Chronic insomnia is common in the general population. Its effect on functioning and disability is usually attributed to an underlying condition, so the diagnosis of insomnia does not qualify for award of a disability pension in the United States or Europe. The aim of this study was to investigate whether insomnia, defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, contributed to long-term work disability. Using a historical cohort design, the authors gathered baseline data from a population-based Norwegian health study of 37,308 working-age people not claiming a disability pension through 1995-1997. The outcome was subsequent award of a disability pension (18-48 months after the health screening) as registered by the National Insurance Administration. Insomnia was a strong predictor of subsequent permanent work disability (adjusted odds ratio=3.90, 95% confidence interval: 3.20, 4.76). Sociodemographic and shift-work characteristics had little confounding effect (adjusted odds ratio=3.69, 95% confidence interval: 3.00, 4.53), and this association remained significant after adjustment for psychiatric and physical morbidity and for health-related behaviors (adjusted odds ratio=1.75, 95% confidence interval: 1.40, 2.20). This study suggests that insomnia should receive increased attention as a robust predictor of subsequent work disability.

Adult↗