OBJECTIVE:To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs).
BACKGROUND:FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally ...been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity.
METHODS:In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen.
RESULTS:Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer.
CONCLUSIONS:FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.
Successful bone tissue engineering requires the understanding of cellular activity in three-dimensional (3D) architectures and how it compares to two-dimensional (2D) architecture. We developed a ...perfusion culture system that utilizes fluid flow to mechanically load a cell-seeded 3D scaffold. This study compared the gene expression of osteoblastic cells in 2D and 3D cultures, and the effects of mechanical loading on gene expression in 2D and 3D cultures. MC3T3-E1 osteoblastlike cells were seeded onto 2D glass slides and 3D calcium phosphate scaffolds and cultured statically or mechanically loaded with fluid flow. Gene expression of OPN and FGF-2 was upregulated at 24 h and 48 h in 3D compared with 2D static cultures, while collagen 1 gene expression was downregulated. In addition, while flow increased OPN in 2D culture at 48 h, it decreased both OPN and FGF-2 in 3D culture. In conclusion, gene expression is different between 2D and 3D osteoblast cultures under static conditions. Additionally, osteoblasts respond to shear stress differently in 2D and 3D cultures. Our results highlight the importance of 3D mechanotransduction studies for bone tissue engineering applications.
Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to ...predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring in 74% of 27 biologically malignant tumors but only 10% of 61 clinically benign tumors. The size of the strumal component rather than the overall size of the ovarian teratoma also had some predictive value. Tumors with a strumal component < or =6 cm recurred rarely (7%), whereas 33% of the consult and 88% of the literature cases > or =12 cm were clinically malignant. Except for a papillary pattern or poorly differentiated cancer, no microscopic feature reliably predicted the clinical outcome, including those typically associated with malignancy in primary thyroid tumors. Among the consult cases, 7% with histologic follicular adenomas and 29% with papillary carcinomas were clinically malignant. Unequivocal vascular invasion was rare, precluding assessment of its effect. Optically clear nuclei, when extensive, were useful to diagnose papillary carcinoma, but were present nevertheless in smaller numbers in both macrofollicular and microfollicular adenomas. Eight tumors confined initially to the ovary (stage 1) recurred. Papillary carcinomas recurred earlier (average 4 y) than follicular adenomatous neoplasms (average 11 y, range: 1-29 y). Overall, the survival rate for all patients was 89% at 10 years and 84% at 25 years, indicating the need for routine long-term follow-up.
Maintaining cellular viability in vivo and in vitro is a critical issue in three-dimensional bone tissue engineering. While the use of osteoblast/endothelial cell cocultures on three-dimensional ...constructs has shown promise for increasing in vivo vascularization, in vitro maintenance of cellular viability remains problematic. This study used perfusion flow to increase osteogenic and angiogenic gene expression, decrease hypoxic gene expression, and increase cell and matrix coverage in osteoblast/endothelial cell co-cultures. Mouse osteoblast-like cells (MC3T3-E1) were cultured alone and in co-culture with mouse microvascular endothelial cells (EOMA) on three-dimensional scaffolds for 1, 2, 7, and 14 days with or without perfusion flow. mRNA levels were determined for several osteogenic, angiogenic, and hypoxia-related genes, and histological analysis was performed. Perfusion flow downregulated hypoxia-related genes (HIF-1α, VEGF, and OPN) at early timepoints, upregulated osteogenic genes (ALP and OCN) at 7 days, and downregulated RUNX-2 and VEGF mRNA at 14 days in osteoblast monocultures. Perfusion flow increased cell number, coverage of the scaffold perimeter, and matrix area in the center of scaffolds at 14 days. Additionally, perfusion flow increased the length of endothelial cell aggregations within co-cultures. These suggest perfusion stimulated co-cultures provide a means of increasing osteogenic and angiogenic activity.
This book includes a collection of essays that explore the relationship between Disability Studies and literary ecocriticism, particularly as this relationship plays out in American literature and ...culture. The contributors to this collection operate from the premise that there is much to be gained for both fields by putting them in conversation, and they do so in a variety of ways. In this manner, the collection contributes to what Joni Adamson and Scott Slovic have referred to as a “third wave of ecocriticism.” Adamson and Slovic attribute the rise of this “third wave” to the richly diverse contributions to ecocriticism over the past decade by scholars intent on including postmodernism, ecofeminism, transnationalism, globalization, and postcolonialism into ecocritical discussions. The essays in Toward an Ecosomatic Paradigm extend this approach of this “third wave” by analyzing disability from an “environmental point of view” while simultaneously examining the environmental imagination from a disability studies perspective. More specifically, the goal of the collection is to investigate the role that literary narratives play in fostering the “ecosomatic paradigm.” As a theoretical framework, the ecosomatic paradigm underscores the dynamic and inter-relational process wherein human mind-bodies interact with the places, both built and wild, they inhabit. That is, the ecosomatic paradigm proceeds from the assumption that nature and culture are meshed in an ongoing and deep relationship that has implications for both the human subject and the natural world. An ecosomatic approach highlights the profound overlap between embodiment and emplacement, and is therefore enriched by both disability studies and ecocritical insight. By drawing on points of confluence between disability studies and ecological criticism, the various ecosomatic readings in this collection challenge normative (even ableist) constructions of the body-environment dyad by complicating and expanding our understanding of this relationship as it is represented in American literature and culture. Collectively, the essays in this book augment the American environmental imagination by highlighting the relationship between disability and the environment as reflected in American literary texts across multiple periods and genres.
An Instructive Case of Cerebral Mucormycosis Shao, Belinda; Hagan, Matthew J; Sastry, Rahul A ...
Medicine and health, Rhode Island,
03/2022, Letnik:
105, Številka:
2
Journal Article
Recenzirano
BACKGROUND: Mucormycosis can lead to fatal rhinocerebral infection. CASE: A 53-year-old male with diabetes presented with altered mental status. He had been recently discharged from an admission for ...COVID-19 pneumonia treated with remdesivir and methylprednisolone. Imaging demonstrated a large left frontal mass with midline shift suspicious for a primary brain neoplasm. His neurologic exam rapidly declined and the patient was taken to the operating room for decompressive hemicraniectomy. Post-operatively, the patient remained comatose and failed to improve. Autopsy revealed a cerebral mucormycosis infection. DISCUSSION: Despite concern for a primary brain neoplasm the patient was diagnosed postmortem with a mucormycosis infection. Other features supporting this diagnosis included nasal sinusitis on initial scans, his fulminant clinical decline, rapidly progressive imaging findings, and persistent hyperglycemia throughout his clinical course. CONCLUSION: In an era of high steroid usage to treat COVID-19, mucormycosis infection must be considered in high-risk patients demonstrating disproportionate clinical decline.
An Instructive Case of Cerebral Mucormycosis Shao, Belinda; Hagan, Matthew J; Sastry, Rahul A ...
Rhode Island medical journal (2013),
2022-Mar-01, 20220301, Letnik:
105, Številka:
2
Journal Article
Recenzirano
Mucormycosis can lead to fatal rhinocerebral infection.
A 53-year-old male with diabetes presented with altered mental status. He had been recently discharged from an admission for COVID-19 pneumonia ...treated with remdesivir and methylprednisolone. Imaging demonstrated a large left frontal mass with midline shift suspicious for a primary brain neoplasm. His neurologic exam rapidly declined and the patient was taken to the operating room for decompressive hemicraniectomy. Post-operatively, the patient remained comatose and failed to improve. Autopsy revealed a cerebral mucormycosis infection.
Despite concern for a primary brain neoplasm the patient was diagnosed postmortem with a mucormycosis infection. Other features supporting this diagnosis included nasal sinusitis on initial scans, his fulminant clinical decline, rapidly progressive imaging findings, and persistent hyperglycemia throughout his clinical course.
In an era of high steroid usage to treat COVID-19, mucormycosis infection must be considered in high-risk patients demonstrating disproportionate clinical decline.
The seismic response and performance of pile-supported wharves on sloping ground is not well documented due to an historical lack of instrumentation on port structures. Although general surface ...observations have been made at numerous ports following recent earthquakes, much more specific soil foundation-structure-interaction data could have been obtained with the more widespread employment of instrumentation. This paper presents the results of empirical and numerical analyses of recorded strong-motion data (SMD) from an array of instruments located on a pile-supported wharf and in the adjacent free field. Data were recorded with an instrumentation array at Berth 24/25 at the Port of Oakland, California, during the M7.0 Loma Prieta earthquake. The primary objectives of this project were to evaluate the SMD and identify the limitations inherent in capturing the complete dynamic character, including soil structure interaction, of a pier or wharf with a structural model. The project is expected to serve the professional engineering community by providing guidance in selecting appropriate techniques for seismic analysis and subsequent upgrade of existing port facilities.
Astronauts and patients on bedrest are subject to a combination of bone strength losses and muscle atrophy due to microgravity and unloading. In this study, mice were subject to both hind limb ...suspension and cast mediated immobilization. Pre-treatment and post-treatment microCT scans were utilized to create finite element models. Both pre-treatment and posttreatment scans were then cropped, rotated and threedimensional image registration was performed to eliminate inconsistency in alignment. A hexahedral finite element mesh was then generated from this 3D data. Finite element analysis was conducted to perform simulated physiological loading of the femoral neck to assess bone strength through bone structural morphology. Hind limb suspension combined with Cast Mediated Immobilization caused a 7.9% decrease in bone FEA stiffness compared to the in-vivo pre-treatment control. No differences were found in bone volume or structural efficiency.
Purpose
Physician wellbeing is critical to maximize patient experience, quality of care, and healthcare value. Objective measures to guide and assess efficacy of interventions in terms of enhanced ...thriving (as opposed to just decreased pathology) have been limited. Here we provide early data on modifiable targets, potential interventions, and comparative impact.
Methods
In this cross-sectional survey-based study of mixed-level residents at 16 academic General Surgery training programs, gender-identity, race, post-graduate year, and gap years were self-reported. Correlation between our primary outcome variable, flourishing, and measures of resilience (mindfulness, personal accomplishment PA, workplace support, workplace control) and risk (depression, emotional exhaustion, depersonalization, perceived stress, anxiety, workplace demand) were assessed.
Results
Of 891 recipients, 300 responded (60% non-male, 41% non-white). Flourishing was significantly positively correlated with all measured resilience factors and negatively correlated with all measured risk factors. In multivariable modelling, mindfulness, PA, and workplace support were positively and significantly associated with flourishing, with PA having the strongest resilience effect. Depression and anxiety were negatively and significantly associated with flourishing, with depression having the strongest risk effect.
Conclusions
Our results suggest that interventions that increase mindfulness, workplace support, and PA, as well as those that decrease depression and anxiety may particularly impact flourishing (i.e., global wellbeing) in surgical trainees. These findings provide preliminary guidance on allocation of resources toward wellbeing interventions. In particular, cognitive (i.e., mindfulness) training is a feasible intervention with modest but significant association with flourishing, and potential indirect effects through influence on PA, anxiety and depression.
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