Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP

Background: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. Methods: Data from the population-based, case-only North Carolina–Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. Results: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). Conclusions: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer

Predicting at-risk opioid use three months after ed visit for trauma: Results from the AURORA study

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making

Measuring variations in optical imaging markers in a glial cell-directed mouse model of human MEN1 syndrome

Gastrointestinal neuroendocrine tumors (GI-NETs) including gastric carcinoids and duodenal neuroendocrine tumors (DNETs), represent a growing class of cancer.1 There is a strong need for intraoperative localization to facilitate diagnosis and treatment of DNETs, particularly those related to the hereditary MEN1 syndrome. However, these demands are precluded by a lack of in vivo model systems that accurately recapitulate disease heterogeneity and progression. Optical imaging markers are commonly used diagnostically to probe early tissue changes that occur with the onset of cancer. Promising techniques include autofluorescence imaging (AFI), which probes intrinsic biochemistry and metabolic markers, and optical coherence tomography (OCT), which provides a robust microstructural reference. Both have demonstrated widespread promise for non-invasive disease screening, making them potential candidates for localization of DNETs. Here we apply AFI and OCT to a mouse model of human MEN1 syndrome to identify unique optical markers associated with neuroendocrine cell reprogramming. Using Cre-lox technology, we generated a glial cell-directed Men1 knockout mouse model that exhibits enhanced neuroendocrine cell differentiation in the stomach and duodenum. We measured variations in optical imaging markers using AFI and OCT images of transgenic and wild type mice. The transgenic lines exhibit significant fluctuations in optical imaging markers compared to wild type mice, both in the scope of AFI and OCT (p<0.01). These results suggest that AFI and OCT may further inform biological and metabolic changes associated with initial neuroendocrine cell reprogramming prefacing tumor formation. Further studies are needed to fully elucidate the significance of these optical markers in GI-NET pathogenesis. Copyright © 2022 SPIE.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia

Background & Aims: Helicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia. To determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum. Methods: Mouse lines were created to conditionally direct IL1β or IFN-γ to the antrum using the Gastrin-CreERT2 and Tet activator. Primary cilia, which transduces HH signaling, on G cells were disrupted by deleting the ciliary motor protein KIF3a. Phenotypic changes were assessed by histology and western blots. A subclone of GLUTag enteroendocrine cells selected for gastrin expression and the presence of primary cilia was treated with recombinant SHH, IL1β or IFN-γ with or without kif3a siRNA. Results: IFN-γ increased gastrin and induced antral hyperplasia. However, antral expression of IL1β suppressed tissue and serum gastrin, while also inducing antral hyperplasia. IFN-γ treatment of GLUTAg cells suppressed GLI2 and induced gastrin, without affecting cilia length. By contrast, IL1β treatment doubled primary cilia length, induced GLI2 and suppressed gastrin gene expression. Knocking down kif3a in GLUTAg cells mitigated SHH or IL1β suppression of gastrin. Conclusions: Overexpression of IL1β in the antrum was sufficient to induce antral hyperplasia coincident with suppression of gastrin via primary cilia. ORCID: #0000-0002-6559-8184 © 2021 The AuthorsOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Multi-band fluorescence imaging and cell collection device for in vivo tumor characterization and growth assessment in xenograft mouse models

Mouse models are essential tools for understanding cancer growth and accelerating the development of therapeutic and diagnostic technologies. Xenografts, generated by implanting tumor cells directly into mice through injection, are frequently used to study cancer biology and therapeutics. In these models, assessment of tumor growth and development is necessary to support the study of disease progression and model validation. Unfortunately, such measurements often require sacrificing the animal to create organ explants or tissue cultures, resulting in increased animal use and hampering longitudinal measurements of individual tumors. A tool enabling in vivo tumor monitoring for xenograft models could improve the efficiency of these animal models and provide more robust growth measurements through true longitudinal measurement. One method of optical tumor assessment involves tagging biomolecules of interest with fluorescent species to enable detection with minimally invasive fluorescence imaging, implemented endoscopically or laparoscopically. However, utilizing fluorescence imaging in vivo in murine models poses challenges due to both tortuous anatomy and small gastrointestinal lumen caliber. This work reports a miniature fluorescence imaging probe equipped with a multiband filter and biopsy device to image and sample fluorescently-tagged, xenografted tumors as they develop in mouse models. We present the design and characterization of the device and report measurements of the modulation transfer function and ex vivo imaging performance, demonstrating its promise as a valuable research tool to advance cancer research in xenograft models, enabling the development of imaging biomarkers for cancer detection in a clinical setting without the need for exogenous contrast. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Evaluation of tile artifact correction methods for multiphoton microscopy mosaics of whole-slide tissue sections

Multi-photon microscopy (MPM) is a useful biomedical imaging tool due, in part, to its capabilities of probing tissue biomarkers at high resolution and with depth-resolved capabilities. Automated MPM tile scanning allows for whole-slide image acquisition but suffers from tile-stitching artifacts that prevent accurate quantitative data analysis. We have investigated a variety of post-processing artifact correction methods using ImageJ macros and custom Python/ MATLAB code and present a quantitative and qualitative comparison of these methods using whole-slide MPM autofluorescence images of human duodenal tissue. Image quality is assessed via evaluation of artifact removal compared to the calculated mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) of the processed image and its raw counterpart. Consideration of both quantitative and qualitative results suggest a combination of flat-field based correction and frequency filtering processing steps provide improved artifact correction when compared to each method used independently to correct for tiling artifacts of tile-scan MPM images. © 2022 SPIE.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Combined flat-field and frequency filter approach to correcting artifacts of multichannel two-photon microscopy

Significance: Multiphoton microscopy (MPM) is a useful biomedical imaging tool for its ability to probe labeled and unlabeled depth-resolved tissue biomarkers at high resolution. Automated MPM tile scanning allows for whole-slide image acquisition but can suffer from tile-stitching artifacts that prevent accurate quantitative data analysis. Aim: We have investigated postprocessing artifact correction methods using ImageJ macros and custom Python code. Quantitative and qualitative comparisons of these methods were made using whole-slide MPM autofluorescence and second-harmonic generation images of human duodenal tissue. Approach: Image quality after artifact removal is assessed by evaluating the processed image and its unprocessed counterpart using the root mean square error, structural similarity index, and image histogram measurements. Results: Consideration of both quantitative and qualitative results suggest that a combination of a custom flat-field-based correction and frequency filtering processing step provide improved artifact correction when compared with each method used independently to correct for tiling artifacts of tile-scan MPM images. Conclusions: While some image artifacts remain with these methods, further optimization of these processing steps may result in computational-efficient methods for removing these artifacts that are ubiquitous in large-scale MPM imaging. Removal of these artifacts with retention of the original image information would facilitate the use of this imaging modality in both research and clinical settings, where it is highly useful in collecting detailed morphologic and optical properties of tissue. © 2024 The Authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]