Publications by authors named "Sandy M"

Article Synopsis
  • ) Drug efflux transporters, like P-glycoprotein (P-gp), play a crucial role in how drugs are absorbed and their potential toxicity, but their interaction with gut microbial metabolites is not fully understood.
  • ) Research found that a specific gut bacterium from the Actinobacterium family enhances drug absorption in mice by producing a factor that inhibits P-gp’s activity.
  • ) The study also identified genes linked to this inhibition and highlighted certain small polar metabolites that could be key players, stressing the need to consider gut microbiota in drug metabolism beyond just what happens in the liver.
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The ten key characteristics (KCs) of carcinogens are based on characteristics of known human carcinogens and encompass many types of endpoints. We propose that an objective review of the large amount of cancer mechanistic evidence for the chemical bisphenol A (BPA) can be achieved through use of these KCs. A search on metabolic and mechanistic data relevant to the carcinogenicity of BPA was conducted and web-based software tools were used to screen and organize the results.

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Objectives: On December 11, 2019, California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) met to consider the addition of cannabis smoke and Δ -THC to the Proposition 65 list as causing reproductive toxicity (developmental endpoint). As the lead state agency for implementing Proposition 65, the Office of Environmental Health Hazard Assessment (OEHHA) reviewed and summarized the relevant scientific literature in the form of a hazard identification document (HID). Here we provide reviews based on the HID: shortened, revised, and reformatted for a larger audience.

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Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism.

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This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ -tetrahydrocannabinol (Δ -THC) that lead to behavioral and other adverse outcomes (AOs). This is Part III in a set of reviews highlighting the animal-derived data considered by California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) in 2019. The Hazard Identification Document (HID) provided to the DARTIC included a summary of human, whole animal, and mechanistic data on the neurodevelopmental toxicity of cannabis smoke and Δ -THC.

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This review focuses on neurodevelopmental effects observed in animal studies of cannabis smoke and Δ -THC. Effects in offspring after preconceptional, prenatal, or perinatal exposure to cannabis smoke or Δ -THC were considered. Locomotor and exploratory behavior effects were noted in rats.

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Fungal symbionts living inside plant leaves ("endophytes") can vary from beneficial to parasitic, but the mechanisms by which the fungi affect the plant host phenotype remain poorly understood. Chemical interactions are likely the proximal mechanism of interaction between foliar endophytes and the plant, as individual fungal strains are often exploited for their diverse secondary metabolite production. Here, we go beyond single strains to examine commonalities in how 16 fungal endophytes shift plant phenotypic traits such as growth and physiology, and how those relate to plant metabolomics profiles.

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B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas.

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Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E.

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Many nitrosamines are potent carcinogens, with more than 30 listed under California's Proposition 65. Recently, nitrosamine contamination of commonly used drugs for treatment of hypertension, heartburn, and type 2 diabetes has prompted numerous Food and Drug Administration (FDA) recalls in the US. These contaminants include the carcinogens NDMA (N-nitrosodimethylamine) and NDEA (N-nitrosodiethylamine) and the animal tumorigen NMBA (N-nitroso-N-methyl-4-aminobutyric acid).

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P2RY8 promotes the confinement and growth regulation of germinal center (GC) B cells, and loss of human P2RY8 is associated with B cell lymphomagenesis. The metabolite -geranylgeranyl-l-glutathione (GGG) is a P2RY8 ligand. The mechanisms controlling GGG distribution are poorly understood.

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Objectives: The US National Toxicology Program (NTP) recently recommended in its Report on Carcinogens Monograph for Antimony Trioxide that antimony trioxide be listed as '' based on sufficient evidence of carcinogenicity in experimental animals and supporting evidence from mechanistic studies. Our goal was to estimate the possible human cancer risk from occupational exposure to antimony trioxide.

Methods: We selected data from 2-year inhalation studies in male and female mice conducted by the NTP and performed cancer dose-response analyses using cancer models and benchmark dose methods developed by the US Environmental Protection Agency.

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Purpose Of Review: Cannabis exposure during critical windows of development may have intergenerational physiological consequences disrupting epigenetic programming and marks. This review examines the literature relating to pre-gestational and prenatal cannabinoid exposure and its effect on genes and molecular pathways related to the development of psychiatric disease.

Recent Findings: Developmental cannabis exposure alters epigenetic processes with functional gene consequences.

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The key characteristics (KC) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs. We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification.

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Coumarin is a naturally occurring sweet-smelling benzopyrone that may be extracted from plants or synthesized for commercial uses. Its uses include as a flavoring agent, fragrance enhancer, and odor-masking additive. We reviewed and evaluated the scientific evidence on the carcinogenicity of coumarin, integrating information from carcinogenicity studies in animals with mechanistic and other relevant data, including data from toxicogenomic, genotoxicity, and metabolism studies, and studies of human variability of a key enzyme, CYP2A6.

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Cancer development from exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated.

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Background: No instruments are currently available to assess nursing students' maintenance of situation awareness. The aim of this study was to develop and validate the Performance-Based Situation Awareness Observation Schedule for measuring nursing students' use of situation awareness.

Method: Twelve expert clinicians participated in a qualitative, reiterative consensus-driven process to establish the content validity of the tool.

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This study compared final year nursing students' error rate and use of strategies to maintain SA when undertaking specific nursing care in a simulated clinical environment pre and 10 weeks post a planned SA education intervention. Students were observed using a Performance Based Situation Awareness Observation Schedule (PBSAOS) undertaking two tasks in a simulated clinical environment pre and post the SA education. For task 1, post educational intervention, there was no significant increase in the error rate for any performance measures, and there were significant decreases in the error rates for three performance measures.

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We developed an integrated, modular approach to predicting chemical toxicity relying on in vitro assay data, linkage of molecular targets to disease categories, and software for ranking chemical activity and examining structural features (chemotypes). We evaluate our approach in a proof-of-concept exercise to identify and prioritize chemicals of potential carcinogenicity concern. We identified 137 cancer pathway-related assays from a subset of U.

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Purpose The purpose of this paper is to understand the perceptions and experiences of healthcare managers working within a community and ambulatory health service who manage poorly performing staff and, to identify the supports, and gaps in supports, that are available to these managers. Design/methodology/approach Data were collected via two focus groups using a semi-structured schedule. The data were transcribed, themed and conclusions summarised.

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Course-based undergraduate research experiences (CUREs) provide a promising avenue to attract a larger and more diverse group of students into research careers. CUREs are thought to be distinctive in offering students opportunities to make discoveries, collaborate, engage in iterative work, and develop a sense of ownership of their lab course work. Yet how these elements affect students' intentions to pursue research-related careers remain unexplored.

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Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors.

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Background: Several studies report that patient safety skills, especially non-technical skills, receive scant attention in nursing curricula. Hence, there is a compelling reason to incorporate material that enhances non-technical skills, such as situation awareness, in nursing curricula in order to assist in the reduction of healthcare related adverse events.

Objectives: The objectives of this study were to: 1) understand final year nursing students' confidence in their patient safety skills; and 2) examine the impact of situation awareness training on final year nursing students' confidence in their patient safety skills.

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Bacteria often produce siderophores to facilitate iron uptake. One of the most studied siderophores is enterobactin, the macrolactone trimer of 2,3-dihydroxybenzoyl-l-serine, produced by E. coli and many other enteric bacteria.

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