Dose-Related Mutagenic and Clastogenic Effects of Benzo[]fluoranthene in Mouse Somatic Tissues Detected by Duplex Sequencing and the Micronucleus Assay.

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28 day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage.

Prehospital Trauma Compendium: Fluid Resuscitation in Trauma - a Position Statement and Resource Document of NAEMSP.

Fluid resuscitation choices in prehospital trauma care are limited, with most Emergency Medical Services (EMS) agencies only having access to crystalloids. Which solution to use, how much to administer, and judging the individual risks and benefits of giving or withholding fluids remains an area of uncertainty. To address the role of crystalloid fluids in prehospital trauma care, we reviewed the available relevant literature and developed recommendations to guide clinical care.

Multi-task Bayesian model combining FDG-PET/CT imaging and clinical data for interpretable high-grade prostate cancer prognosis.

We propose a fully automatic multi-task Bayesian model, named Bayesian Sequential Network (BSN), for predicting high-grade (Gleason   8) prostate cancer (PCa) prognosis using pre-prostatectomy FDG-PET/CT images and clinical data. BSN performs one classification task and five survival tasks: predicting lymph node invasion (LNI), biochemical recurrence-free survival (BCR-FS), metastasis-free survival, definitive androgen deprivation therapy-free survival, castration-resistant PCa-free survival, and PCa-specific survival (PCSS). Experiments are conducted using a dataset of 295 patients.

Characterizing the Areal Extent of PFAS Contamination in Fish Species Downgradient of AFFF Source Zones.

Most monitoring programs next to large per- and polyfluoroalkyl substances (PFAS) sources focus on drinking water contamination near source zones. However, less is understood about how these sources affect downgradient hydrological systems and food webs. Here, we report paired PFAS measurements in water, sediment, and aquatic biota along a hydrological gradient away from source zones contaminated by the use of legacy aqueous film-forming foam (AFFF) manufactured using electrochemical fluorination.

Physician perspectives about the diagnosis and management of acute chest syndrome.

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS.

Study Design And Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States.

Power analyses to inform Duplex Sequencing study designs for MutaMouse liver and bone marrow.

Regulatory genetic toxicology testing is essential for identifying potentially mutagenic hazards. Duplex Sequencing (DS) is an error-corrected next-generation sequencing technology that provides substantial advantages for mutation analysis over conventional mutagenicity assays including: improved accuracy of mutation detection, ability to measure changes in mutation spectrum, and applicability across diverse biological models. To apply DS for regulatory toxicology testing, power analyses are required to determine suitable sample sizes and study designs.

Dose-related Mutagenic and Clastogenic Effects of Benzo[b]fluoranthene in Mouse Somatic Tissues Detected by Duplex Sequencing and the Micronucleus Assay.

Unlabelled: Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[ ]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28-day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage.

Improving Care for Older Adults with Cancer in Canada: A Call to Action.

Most patients diagnosed with and dying from cancer in Canada are older adults, with aging contributing to the large projected growth in cancer incidence. Older adults with cancer have unique needs, and on a global scale increasing efforts have been made to address recognized gaps in their cancer care. However, in Canada, geriatric oncology remains a new and developing field.

Barriers to integrating portable Magnetic Resonance Imaging systems in emergency medical service ambulances for stroke care.

This study examines the barriers to integrating portable Magnetic Resonance Imaging (MRI) systems into ambulance services to enable effective triaging of patients to the appropriate hospitals for timely stroke care and potentially reduce door-to-needle time for thrombolytic administration. The study employs a qualitative methodology using a digital twin of the patient handling process developed and demonstrated through semi-structured interviews with 18 participants, including 11 paramedics from an Emergency Medical Services system and seven neurologists from a tertiary stroke care centre. The interview transcripts were thematically analysed to determine the barriers based on the Systems Engineering Initiative for Patient Safety framework.

Bioconcentration of Per- and Polyfluoroalkyl Substances and Precursors in Fathead Minnow Tissues Environmentally Exposed to Aqueous Film-Forming Foam-Contaminated Waters.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with toxicity in wildlife and negative health effects in humans. Decades of fire training activity at Joint Base Cape Cod (MA, USA) incorporated the use of aqueous film-forming foam (AFFF), which resulted in long-term PFAS contamination of sediments, groundwater, and hydrologically connected surface waters. To explore the bioconcentration potential of PFAS in complex environmental mixtures, a mobile laboratory was established to evaluate the bioconcentration of PFAS from AFFF-impacted groundwater by flow-through design.

The comparability tales: A phase-appropriate roadmap for CGT drug product development.

Cell and gene therapies (CGTs) have revolutionized patient outcomes and provided care options for previously untreatable conditions. The clinical and commercial progress of CGT therapies is hindered by chemistry, manufacturing, and control (CMC) challenges. This article summarizes recommendations from the 2023 Annual Meeting CMC sessions wherein speakers advocated for science-driven comparability strategies, proactive risk assessments, clearer regulatory guidance, and a shift from retrospective to prospective studies.

Key Considerations for the Treatment of Advanced Breast Cancer in Older Adults: An Expert Consensus of the Canadian Treatment Landscape.

The prevalence of breast cancer amongst older adults in Canada is increasing. This patient population faces unique challenges in the management of breast cancer, as older adults often have distinct biological, psychosocial, and treatment-related considerations. This paper presents an expert consensus of the Canadian treatment landscape, focusing on key considerations for optimizing selection of systemic therapy for advanced breast cancer in older adults.

A Single-Center 18-Year Series of 73 Cases of Metaplastic Carcinoma of the Breast.

Aim: To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy.

Methods: This retrospective study included patients with MeBC ( = 73) from a tertiary breast cancer center: the "Centre des Maladies du Sein of the CHU de Québec-Université Laval." The specimens were reviewed by two pathologists.

Hypothalamic neuronal outputs transmit sensorimotor signals at the onset of locomotor initiation.

The lateral hypothalamus (LH) plays a critical role in sensory integration to organize behavior responses. However, how projection-defined LH neuronal outputs dynamically transmit sensorimotor signals to major downstream targets to organize behavior is unknown. Here, using multi-fiber photometry, we show that three major LH neuronal outputs projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and lateral habenula (LHb) exhibit significant coherent activity in mice engaging sensory-evoked or self-initiated motor responses.

Mobile point-of-care MRI demonstration of a normal volunteer in a telemedicine-equipped ambulance.

Objective: Several centers have implemented ambulances equipped with CT scanners and telemedicine capabilities, known as mobile stroke units (MSU), to expedite acute stroke care delivery in the pre-hospital setting. While MSUs have been shown to improve outcomes compared with standard emergency medical management, there are limitations to incorporating CT, including radiation exposure to emergency medical services personnel. Recently, a portable, low-field strength MRI (Swoop®, Hyperfine, Inc.

Duplex sequencing provides detailed characterization of mutation frequencies and spectra in the bone marrow of MutaMouse males exposed to procarbazine hydrochloride.

Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide substantial advantages over conventional mutagenicity assays. DS could be used to eliminate reliance on standalone reporter assays and provide mechanistic information alongside mutation frequency (MF) data.

Centurial Persistence of Forever Chemicals at Military Fire Training Sites.

Drinking water contamination by per- and polyfluoroalkyl substances (PFAS) is widespread near more than 300 United States (U.S.) military bases that used aqueous film-forming foams (AFFF) for fire training and firefighting activities.

Uptake of Per- and Polyfluoroalkyl Substances by Fish, Mussel, and Passive Samplers in Mobile-Laboratory Exposures Using Groundwater from a Contamination Plume at a Historical Fire Training Area, Cape Cod, Massachusetts.

Aqueous film-forming foams historically were used during fire training activities on Joint Base Cape Cod, Massachusetts, and created an extensive per- and polyfluoroalkyl substances (PFAS) groundwater contamination plume. The potential for PFAS bioconcentration from exposure to the contaminated groundwater, which discharges to surface water bodies, was assessed with mobile-laboratory experiments using groundwater from the contamination plume and a nearby reference location. The on-site continuous-flow 21-day exposures used male and female fathead minnows, freshwater mussels, polar organic chemical integrative samplers (POCIS), and polyethylene tube samplers (PETS) to evaluate biotic and abiotic uptake.

Management of Oligometastatic Breast Cancer: An Expert Committee's Opinion.

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion.

Unresolved early post-operative pain trajectory predicts moderate-to-severe persistent pain after breast cancer surgery-An observational cohort study.

Background: Modelling acute post-operative pain trajectories may improve the prediction of persistent pain after breast cancer surgery (PPBCS). This study aimed to investigate the predictive accuracy of early post-operative pain (EPOP) trajectories in the development of PPBCS.

Materials & Methods: This observational study was conducted in a French Comprehensive Cancer Centre and included patients who underwent breast cancer surgery from December 2017 to November 2018.

Characteristics of Interval Colorectal Cancer: A Canadian Retrospective Population-Level Analysis from Newfoundland and Labrador.

Interval colorectal cancers (I-CRCs) arise during the interval time period between scheduled colonoscopies. Predicting which patients are at risk of I-CRCs remains an elusive undertaking, but evidence would suggest that most I-CRCs arise from lesions missed on index endoscopy. The procedural factors that lead to missed lesions are numerous and lack consensus in the literature.

Duplex sequencing identifies genomic features that determine susceptibility to benzo(a)pyrene-induced in vivo mutations.

Exposure to environmental mutagens increases the risk of cancer and genetic disorders. We used Duplex Sequencing (DS), a high-accuracy error-corrected sequencing technology, to analyze mutation induction across twenty 2.4 kb intergenic and genic targets in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP), a widespread environmental pollutant.