Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.

MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type-specific enhancer leads to increased MYC expression.

The financial and environmental impact of unopened medical supplies discarded in the emergency department.

Background: Inefficient supply chain management within the US healthcare industry results in significant financial and environmental impact. Unopened medical supplies may routinely be discarded in the Emergency Department (ED), contributing as a source of unnecessary medical waste.

Objectives: Quantify the financial and environmental impact of unopened medical supplies that are routinely discarded in two EDs.

An ethologically relevant paradigm to assess defensive response to looming visual contrast stimuli.

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice.

Mitochondrial quality control in non-exudative age-related macular degeneration: From molecular mechanisms to structural and functional recovery.

Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality.

An ethologically relevant paradigm to assess visual contrast sensitivity in rodents.

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice.

The Climate Impact of Medical Residency Interview Travel in the United States and Canada: A Scoping Review.

The change from in-person to virtual interviews for graduate medical education (GME) provides the opportunity to compare the potential environmental effects. To explore and summarize the existing literature on the potential climate impact of medical residency interview travel through a scoping review. The search was conducted in October 2022 using 5 research databases.

PCNEO, a New Proficiency Testing Program for Flow Cytometric Analysis of Plasma Cell Neoplasms From the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee.

Context.—: In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program-PCNEO-to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group.

Objective.

Heterogeneity of B cell lymphopoiesis in patients with premalignant and active myeloma.

To better characterize the heterogeneity of multiple myeloma (MM), we profiled plasma cells (PCs) and their B cell lymphopoiesis in the BM samples from patients with monoclonal gammopathy of undetermined significance, smoldering MM, and active MM by mass cytometry (CyTOF) analysis. Characterization of intra- and interneoplastic heterogeneity of malignant plasmablasts and PCs revealed overexpression of the MM SET domain (MMSET), Notch-1, and CD47. Variations in upregulation of B cell signaling regulators (IFN regulatory factor 4 [IRF-4], CXCR4, B cell lymphoma 6 [Bcl-6], c-Myc, myeloid differentiation primary response protein 88 [MYD88], and spliced X box-binding protein 1 [sXBP-1]) and aberrant markers (CD319, CD269, CD200, CD117, CD56, and CD28) were associated with different clinical outcomes in clonal PC subsets.

Early life stress induces visual dysfunction and retinal structural alterations in adult mice.

Early life stress (ELS) is defined as a period of severe and/or chronic trauma, as well as environmental/social deprivation or neglect in the prenatal/early postnatal stage. Presently, the impact of ELS on the retina in the adult stage is unknown. The long-term consequences of ELS at retinal level were analyzed in an animal model of maternal separation with early weaning (MSEW), which mimics early life maternal neglect.

Non-Hodgkin lymphoma mimicking acute leukemia: a report of six cases and review of the literature.

Aggressive subtypes of non-Hodgkin lymphoma may uncommonly be referred to clinical oncologists for treatment of acute leukemia, due to an elevated or rapidly rising white blood cell count (WBC), with circulating neoplastic cells that morphologically resemble leukemic blasts seen in acute myeloid or lymphoblastic leukemia. We describe six cases of non-Hodgkin lymphoma that mimicked acute leukemia and were identified in the pathology records of the Brigham and Women's Hospital. The patients were older adults (mean age 70 years), who presented with leukocytosis (mean 79.

Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma.

Oncogenic activated RAS mutations have been detected in 50% of de novo and 70% of relapsed multiple myeloma (MM) patients. Translocation t(11;14) involving IgH/CCDN1 and overexpression of cyclin-Ds are early events in MM pathogenesis, enhancing uncontrolled MM cell growth. We hypothesized that targeting both RAS/MAPK pathway molecules including Erk1/2 along with cyclin-Ds enhances MM cytotoxicity and minimizes side effects.

A novel viewpoint in glaucoma therapeutics: enriched environment.

Glaucoma is one of the world's most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their axons. Despite glaucoma's most accepted risk factor is increased intraocular pressure (IOP), the mechanisms behind the disease have not been fully elucidated. To date, IOP lowering remains the gold standard; however, glaucoma patients may still lose vision regardless of effective IOP management.

Enriched environment and visual stimuli protect the retinal pigment epithelium and photoreceptors in a mouse model of non-exudative age-related macular degeneration.

Non-exudative age-related macular degeneration (NE-AMD), the main cause of blindness in people above 50 years old, lacks effective treatments at the moment. We have developed a new NE-AMD model through unilateral superior cervical ganglionectomy (SCGx), which elicits the disease main features in C57Bl/6J mice. The involvement of oxidative stress in the damage induced by NE-AMD to the retinal pigment epithelium (RPE) and outer retina has been strongly supported by evidence.