323 research outputs found

    Underwater Endoscopic Mucosal Resection of Large Duodenal Adenomas (Video)

    Get PDF
    AbstractBackground and aimsEndoscopic mucosal resection (EMR) is a well-established method for the removal of neoplastic polyps throughout the GI tract. EMR typically involves insufflation of the lumen using air or CO2, followed by submucosal lifting of a polyp to minimize the risk of deep tissue injury and perforation, followed by hot-snare polypectomy. Underwater endoscopic mucosal resection (UEMR) is a new technique that uses water to enable lesion visualization in a lumen that is not distended by air or CO2, followed by piecemeal hot-snare resection of large mucosally-based neoplasms. UEMR does not require submucosal injection to create a fluid cushion. Very few published examples of UMER in the duodenum exist. This video case series describes the use of UEMR for the resection of several large duodenal adenomas.ProcedureUnderwater endoscopic mucosal resection was utilized for the removal of several large duodenal adenomas.ResultsThree duodenal lesions ranging from 1.8cm to 5cm were successfully resected by UEMR. The mean time for resection was 18min. There were no adverse events.ConclusionsUEMR is an efficacious technique for the resection of large mucosally-based neoplasms of the duodenum

    (±)-2-exo- and endo-Methylamino-1,2,3,4-tetrahydro-1,4-ethanonapthalene Hydrochloride

    Get PDF
    This is the published version

    Bioactivation of isoxazole-containing bromodomain and extra-terminal domain (BET) inhibitors

    Get PDF
    The 3,5-dimethylisoxazole motif has become a useful and popular acetyl-lysine mimic employed in isoxazole-containing bromodomain and extra-terminal (BET) inhibitors but may introduce the potential for bioactivations into toxic reactive metabolites. As a test, we coupled deep neural models for quinone formation, metabolite structures, and biomolecule reactivity to predict bioactivation pathways for 32 BET inhibitors and validate the bioactivation of select inhibitors experimentally. Based on model predictions, inhibitors were more likely to undergo bioactivation than reported non-bioactivated molecules containing isoxazoles. The model outputs varied with substituents indicating the ability to scale their impact on bioactivation. We selected OXFBD02, OXFBD04, and I-BET151 for more in-depth analysis. OXFBD\u27s bioactivations were evenly split between traditional quinones and novel extended quinone-methides involving the isoxazole yet strongly favored the latter quinones. Subsequent experimental studies confirmed the formation of both types of quinones for OXFBD molecules, yet traditional quinones were the dominant reactive metabolites. Modeled I-BET151 bioactivations led to extended quinone-methides, which were not verified experimentally. The differences in observed and predicted bioactivations reflected the need to improve overall bioactivation scaling. Nevertheless, our coupled modeling approach predicted BET inhibitor bioactivations including novel extended quinone methides, and we experimentally verified those pathways highlighting potential concerns for toxicity in the development of these new drug leads

    Nutrition policy: developing scientific recommendations for food-based dietary guidelines for older adults living independently in Ireland

    Get PDF
    Older adults (≥65 years) are the fastest growing population group. Thus, ensuring nutritional well-being of the ‘over-65s’ to optimise health is critically important. Older adults represent a diverse population – some are fit and healthy, others are frail and many live with chronic conditions. Up to 78% of older Irish adults living independently are overweight or obese. The present paper describes how these issues were accommodated into the development of food-based dietary guidelines for older adults living independently in Ireland. Food-based dietary guidelines previously established for the general adult population served as the basis for developing more specific recommendations appropriate for older adults. Published international reports were used to update nutrient intake goals for older adults, and available Irish data on dietary intakes and nutritional status biomarkers were explored from a population-based study (the National Adult Nutrition Survey; NANS) and two longitudinal cohorts: the Trinity-Ulster and Department of Agriculture (TUDA) and the Irish Longitudinal Study on Ageing (TILDA) studies. Nutrients of public health concern were identified for further examination. While most nutrient intake goals were similar to those for the general adult population, other aspects were identified where nutritional concerns of ageing require more specific food-based dietary guidelines. These include, a more protein-dense diet using high-quality protein foods to preserve muscle mass; weight maintenance in overweight or obese older adults with no health issues and, where weight-loss is required, that lean tissue is preserved; the promotion of fortified foods, particularly as a bioavailable source of B vitamins and the need for vitamin D supplementation

    Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.

    Get PDF
    Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at 40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women
    • …
    corecore