Letting Go of the Status Quo: One Program's Experience Discontinuing Ethics Committees and Creating Alternative Structures for Engagement.

AbstractThe authors describe their Ethics Program's transition from utilizing ethics committees to instead implementing a three-initiative structure consisting of Ethics Grand Rounds, an Ethics Liaison Network, and an Ethics Advisory Group. They first outline the history of ethics committees. Then, they discuss the history of their Ethics Program and the challenges that ethics committees posed.

A Novel CRISPR/Cas9-mediated Mouse Model of Colon Carcinogenesis.

Background & Aims: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities.

Bioethics in Gerontology: Developing a Typology of Ethical Issues in Assisted Living.

Assisted living (AL) simultaneously is home to older adults who cannot live independently and a place where people work and visit and, therefore, where value conflicts are apt to arise. In this report we present the "Typology of Ethical Issues in Assisted Living" with emphasis on its development. The typology derives from a synthesis of frameworks used in acute care spaces adapted and applied to data collected as part of an ethnographic study involving AL residents with dementia.

The oncogenic function of PLAGL2 is mediated via ASCL2 and IGF2 and a Wnt-independent mechanism in colorectal cancer.

Colorectal cancer (CRC) tumorigenesis and progression are linked to common oncogenic mutations, especially in the tumor suppressor , whose loss triggers the deregulation of TCF4/β-Catenin activity. CRC tumorigenesis is also driven by multiple epimutational modifiers such as transcriptional regulators. We describe the common (and near-universal) activation of the zinc finger transcription factor and Let-7 target PLAGL2 in CRC and find that it is a key driver of intestinal epithelial transformation.

How resources affect management of periprosthetic fractures of the distal femur: perspectives from Israel, South Sudan, and South Africa.

Periprosthetic fractures of the distal femur have significant morbidity in both total hip and total knee arthroplasty (THA and TKA, respectively). The incidence of these fractures is growing, with the predominant mechanism of injury being a fall from a standing height and therefore considered fragility fractures. In many countries, improved public funding and a flourishing private health care sector, when coupled with increased life expectancy, translates to more older patients receiving both TKA and THA and therefore an increased prevalence of periprosthetic fractures and their associated complications.

Effective Access to Laboratory Test Results: A Health Equity Issue that Enhances Diagnostic Excellence.

Access to laboratory test results through patient portals is a health equity issue for patients with limited English proficiency (LEP), particularly for Spanish-speaking patients, the largest minority group in the USA. Gaps ranging from linguistic, cultural, and socioeconomic disparities to lack of systematic approaches (e.g.

Becoming Inclusive: Actionable Steps to Diversify the Field of Clinical Ethics.

At the 2022 Clinical Ethics Unconference, the authors perceived a significant lack of racial and ethnic diversity, which was consistent with their experiences in other clinical ethics settings. As a result, they convened a working group to address the pervasive lack of diversity present in the field of clinical ethics and to propose strategies to increase the representation of people from racial and ethnic minority populations. This article identifies the harms associated with the lack of diversity in the healthcare setting and translates these to the field of clinical ethics.

Cas-CLOVER is a novel high-fidelity nuclease for safe and robust generation of T-enriched allogeneic CAR-T cells.

The use of T cells from healthy donors for allogeneic chimeric antigen receptor T (CAR-T) cell cancer therapy is attractive because healthy donor T cells can produce versatile off-the-shelf CAR-T treatments. To maximize safety and durability of allogeneic products, the endogenous T cell receptor and major histocompatibility complex class I molecules are often removed via knockout of T cell receptor beta constant () (or T cell receptor alpha constant []) and , respectively. However, gene editing tools (e.

Erratum: Cas-CLOVER is a novel high-fidelity nuclease for safe and robust generation of T-enriched allogeneic CAR-T cells.

[This corrects the article DOI: 10.1016/j.omtn.

Fathead Minnows Exposed to Organic Compounds from Oil Sands Tailings as Embryos Have Reduced Survival, Impaired Development, and Altered Behaviors That Persist into Larval Stages.

Our study evaluated whether exposure to naphthenic acid fraction compounds (NAFCs) extracted from oil sands process-affected waters (OSPW) has adverse effects on fish embryos that persist into later life. We exposed fathead minnow (Pimephales promelas) embryos to concentrations of NAFCs found in OSPW (2.5-54 mg/L) for 7 days (1 day postfertilization to hatch), then raised surviving larvae in outdoor mesocosms of uncontaminated lake water for 1 month.

Fixation of intertrochanteric femur fractures using the SIGN intramedullary nail augmented by a lateral plate in a resource-limited setting without intraoperative fluoroscopy: assessment of functional outcomes at one-year follow-up at Juba Teaching Hospital.

Objectives: The incidence of hip fracture is high and increasing globally due to an aging population. Morbidity and mortality from these injuries are high at baseline and worse without prompt surgical treatment to facilitate early mobilization. Due to resource constraints, surgeons in low-income countries often must adapt available materials to meet these surgical needs.

Bringing the clinical laboratory into the strategy to advance diagnostic excellence.

Objectives: Clinical laboratory testing provides essential data for making medical diagnoses. Generating accurate and timely test results clearly communicated to the treating clinician, and ultimately the patient, is a critical component that supports diagnostic excellence. On the other hand, failure to achieve this can lead to diagnostic errors that manifest in missed, delayed and wrong diagnoses.

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer.

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution.

Transcriptional responses in newly-hatched Japanese medaka (Oryzias latipes) associated with developmental malformations following diluted bitumen exposure.

Japanese medaka embryos were exposed to water accommodated fractions (WAF) and chemically-enhanced WAF of two types of diluted bitumen (dilbit) at concentrations bracketing the EC50s for developmental malformations. Within these treatments, fish were grouped based on the presence or absence of developmental malformations (e.g.

Effects on Trout Alevins of Chronic Exposures to Chemically Dispersed Access Western Blend and Cold Lake Blend Diluted Bitumens.

The present study assessed the chronic toxicity of 2 chemically enhanced water accommodated fractions (CEWAFs) of diluted bitumens (dilbits), Access Western Blend (AWB) and Cold Lake Blend (CLB), to rainbow trout alevins. Chemical dispersion was used to overcome the resistance to dispersion of dilbits and to generate test solutions that contained more and smaller oil droplets for increased partitioning of petroleum hydrocarbons into water. Test solutions were characterized by fluorescence spectroscopy, a rapid and inexpensive analytical tool to compare toxicity endpoints measured by fluorescence (total petroleum hydrocarbons measured by fluorescence [TPH-F]).

Focal duodenal necrosis in chickens: attempts to reproduce the disease experimentally and diagnostic considerations.

Focal duodenal necrosis (FDN) is an intestinal disease of egg-layer chickens characterized by multifocal necrosis of the duodenal loop and proximal jejunum. Affected flocks usually have decreased egg weights and drops in egg production. Previous studies have associated this condition with infection.

Comparative toxicity of two diluted bitumens to developing yellow perch (Perca flavescens).

Increasing demand for diluted bitumen (dilbit) has led to the development of the oil sands industry and the expansion of transcontinental pipelines. Dilbit is an unresolved complex mixture with variable diluent and bitumen composition. Thus, it is important to understand the effects of the two most transported dilbits in Canada, Access Western Blend (AWB) and Cold Lake Blend (CLB) on a North America native and freshwater fish species, the yellow perch (Perca flavescens).

Interferon-γ directly induces gastric epithelial cell death and is required for progression to metaplasia.

Chronic inflammation of the gastric mucosa, often caused by autoimmune gastritis and/or infection with Helicobacter pylori, can lead to atrophy of acid-secreting parietal cells with metaplasia of remaining cells. The histological pattern marks a critical step in the progression from chronic gastritis to gastric cancer, yet underlying mechanism(s) of inflammation-induced cell death of gastric epithelial cells are poorly understood. We investigated direct effects of a type 1 cytokine associated with autoimmunity and infection, interferon-γ (IFN-γ), on gastric epithelial cells.

Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites.

Many different transcription factors (TFs) regulate gene expression in a combinatorial fashion, often by binding in close proximity to each other on composite regulatory DNA elements. Here, we investigated how ETS TFs bind with the AP1 TFs JUN-FOS at composite DNA-binding sites. DNA-binding ability with JUN-FOS correlated with the phenotype of ETS proteins in prostate cancer.

Morphological and molecular effects of two diluted bitumens on developing fathead minnow (Pimephales promelas).

Canada has experienced a significant increase in the transport of diluted bitumen (dilbit), a predominant oil sands product that combines bitumen with diluents derived from oil-gas condensates and other proprietary compounds. The toxicity of dilbit to fish embryos, which are immobile and thus at a high risk of exposure to oil in the event of a spill, remains largely unknown for most species. This study assessed the toxicity of water accommodated fractions (WAF) and chemically enhanced water accommodated fractions (CEWAF) of two winter dilbit blends, Access Western Blend (AWB) and Cold Lake Blend (CLB), to fathead minnow (Pimephales promelas) embryos.

The LIN28B-IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine.

RNA-binding proteins (RBPs) are expressed broadly during both development and malignant transformation, yet their mechanistic roles in epithelial homeostasis or as drivers of tumor initiation and progression are incompletely understood. Here we describe a novel interplay between RBPs LIN28B and IMP1 in intestinal epithelial cells. Ribosome profiling and RNA sequencing identified as a principle node for gene expression regulation downstream from In vitro and in vivo data demonstrate that epithelial IMP1 loss increases expression of WNT target genes and enhances LIN28B-mediated intestinal tumorigenesis, which was reversed when we overexpressed IMP1 independently in vivo.

The Zinc Finger Transcription Factor PLAGL2 Enhances Stem Cell Fate and Activates Expression of ASCL2 in Intestinal Epithelial Cells.

Intestinal epithelial stem cell (IESC) fate is promoted by two major transcriptional regulators, the TCF4/β-catenin complex and ASCL2, which drive expression of IESC-specific factors, including Lgr5, Ephb2, and Rnf43. Canonical Wnt signaling via TCF4/β-catenin directly transactivates Ascl2, which in turn auto-regulates its own expression. Conversely, Let-7 microRNAs antagonize the IESC lineage by repressing specific mRNA targets.

Effectiveness of Practices to Support Appropriate Laboratory Test Utilization: A Laboratory Medicine Best Practices Systematic Review and Meta-Analysis.

Objectives: To evaluate the effectiveness of practices used to support appropriate clinical laboratory test utilization.

Methods: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practices A6 cycle method. Eligible studies assessed one of the following practices for effect on outcomes relating to over- or underutilization: computerized provider order entry (CPOE), clinical decision support systems/tools (CDSS/CDST), education, feedback, test review, reflex testing, laboratory test utilization (LTU) teams, and any combination of these practices.