A physiologically based pharmacokinetic (PBPK) model describing the kinetics of a commercial mixture α-, β-, and γ-hexabromocyclododecane exposure in mice.

Hexabromocyclododecane (HBCD) is a brominated flame retardant, that is added, but not chemically bonded, to consumer products. HBCD is sold as a commercial-grade HBCD mixture containing three major stereoisomers: alpha (α), beta (β), and gamma (γ), with relative amounts of 12% for α-HBCD, 6% for β-HBCD, and 82% for γ-HBCD. HBCDs are widely measured in the environment and in biological matrices.

Serum Dioxin Levels in a Subset of Participants of the East Palestine, Ohio Train Derailment Health Tracking Study.

A February 3, 2023 train derailment and subsequent burn released hazardous chemicals into East Palestine, Ohio. One potential exposure was polychlorinated dibenzo-p-dioxins, dibenzofurans, and coplanar polychlorinated biphenyls (cPCBs), collectively referred to as dioxins. Many studies have linked dioxins to numerous health effects.

Management of a fractured microcatheter during middle meningeal artery embolization.

Middle meningeal artery embolization (MMAE) is an effective adjunctive treatment for chronic subdural hematomas and carries a low risk of significant complications.1 Here we describe the management of a retained and fractured microcatheter following liquid embolic MMAE. A patient with chronic recurrent subdural hematomas underwent bilateral MMAE with Onyx liquid embolic material (Medtronic).

Dioxins vs. PFAS: Science and Policy Challenges.

Background: Dioxin-like chemicals are a group of ubiquitous environmental toxicants that received intense attention in the last two decades of the 20th century. Through extensive mechanistic research and validation, the global community has agreed upon a regulatory strategy for these chemicals that centers on their common additive activation of a single receptor. Applying these regulations has led to decreased exposure in most populations studied.

Management of a Twisted Flow Diverting Stent With a Balloon Mounted Cardiac Stent in a Pediatric Aneurysm: A Technical Report.

Background And Importance: Giant aneurysms can present technical challenges during treatment with flow diversion including inability to access the aneurysm outflow directly. Encircling the aneurysm with a microwire/microcatheter has been well described; however, it can result in a twisted stent because of catheter twisting during the reduction maneuver, which, in turn, could lead to thromboembolic complications.

Case Presentation: Here, we describe a novel technique to manage the twist of the flow diverter in a giant internal carotid artery aneurysm using a combination of angioplasty and off-label placement of a balloon-mounted cardiac stent within the flow diverter.

Flow Diversion for Endovascular Treatment of Intracranial Aneurysms: Past, Present, and Future Directions.

Flow diversion for intracranial aneurysms emerged as an efficacious and durable treatment option over the last two decades. In a paradigm shift from intrasaccular aneurysm embolization to parent vessel remodeling as the mechanism of action, the proliferation of flow-diverting devices has enabled the treatment of many aneurysms previously considered untreatable. In this review, we review the history and development of flow diverters, highlight the pivotal clinical trials leading to their regulatory approval, review current devices including endoluminal and intrasaccular flow diverters, and discuss current and expanding indications for their use.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

Background: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase.

Methods: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK.

The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists.

Systematic update to the mammalian relative potency estimate database and development of best estimate toxic equivalency factors for dioxin-like compounds.

The World Health Organization (WHO) assesses potential health risks of dioxin-like compounds using Toxic Equivalency Factors (TEFs). This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets).

Development of the Circle of Willis Score (COWS) to help guide decision making during acute tandem occlusion treatment: Preliminary analysis.

Background: Acute tandem occlusions (TOs) are challenging to treat. Although acute carotid stenting of the proximal lesion is well tolerated, there are certain situations when the practitioner may be wary of acute stenting (bleeding concerns).

Objective: The purpose of this study was to retrospectively study patients with tandem occlusions who had re-occlusion of the extracranial ICA and develop a Circle of Willis Score (COWS) to help predict which patients could forego acute stenting.

Opportunities in Assessing and Regulating Organohalogen Flame Retardants (OFRs) as a Class in Consumer Products.

Background: In 2015, the U.S. Consumer Product Safety Commission (CPSC) received and then, in 2017, granted a petition under the Federal Hazardous Substances Act to declare certain groups of consumer products as banned hazardous substances if they contain nonpolymeric, additive organohalogen flame retardants (OFRs).

Double microcatheter reduction using partially deployed Atlas stents in treating a large dysplastic MCA bifurcation aneurysm with Y stent assisted coiling.

Treatment of large dysplastic middle cerebral artery (MCA) aneurysms can be challenging.1 2 Catheterization of M2 branches at hyperacute angles often requires an 'around the world' approach/microcatheter reduction, which can be accomplished with rapid pull,3 balloon anchor,4 and stent anchor5 techniques. In this video video 1, Atlas stents (Stryker) are used for double microcatheter reduction along with Y stent assisted coil embolization (Video 1).

Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

Introduction: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain.

Methods: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association.

European Medicines Agency Conflicts With the European Food Safety Authority (EFSA) on Bisphenol A Regulation.

The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis.

Development and application of a systematic and quantitative weighting framework to evaluate the quality and relevance of relative potency estimates for dioxin-like compounds (DLCs) for human health risk assessment.

The toxic equivalency factors (TEFs) approach for dioxin-like chemicals (DLCs) is currently based on a qualitative assessment of a heterogeneous data set of relative estimates of potency (REPs) spanning several orders of magnitude with highly variable study quality and relevance. An effort was undertaken to develop a weighting framework to systematically evaluate and quantitatively integrate the quality and relevance for development of more robust TEFs. Six main-study characteristics were identified as most important in characterizing the quality and relevance of an individual REP for human health risk assessment: study type, study model, pharmacokinetics, REP derivation method, REP derivation quality, and endpoint.

Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis.

Purpose Of Review: We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling.

Recent Findings: Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated.

Constitutively Synergistic Multiagent Drug Formulations Targeting MERTK, FLT3, and BCL-2 for Treatment of AML.

Purpose: Although high-dose, multiagent chemotherapy has improved leukemia survival rates, treatment outcomes remain poor in high-risk subsets, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in infants. The development of new, more effective therapies for these patients is therefore an urgent, unmet clinical need.

Methods: The dual MERTK/FLT3 inhibitor MRX-2843 and BCL-2 family protein inhibitors were screened in high-throughput against a panel of AML and MLL-rearranged precursor B-cell ALL (infant ALL) cell lines.

Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.

Advances in multiagent chemotherapy have led to recent improvements in survival for patients with acute lymphoblastic leukemia (ALL); however, a significant fraction do not respond to frontline chemotherapy or later relapse with recurrent disease, after which long-term survival rates remain low. To develop new, effective treatment options for these patients, we conducted a series of high-throughput combination drug screens to identify chemotherapies that synergize in a lineage-specific manner with MRX-2843, a small molecule dual MERTK and FLT3 kinase inhibitor currently in clinical testing for treatment of relapsed/refractory leukemias and solid tumors. Using experimental and computational approaches, we found that MRX-2843 synergized strongly-and in a ratio-dependent manner-with vincristine to inhibit both B-ALL and T-ALL cell line expansion.

Effective communications strategies to increase the impact of environmental health research.

Background: Per- and polyfluoroalkyl substances (PFAS) are the subject of a growing body of research with the potential to positively impact public and ecological health. However, to effect positive change, findings must be communicated beyond the scientific community.

Objective: We sought to (a) evaluate the relationships between communications strategy, media attention, and scholarly citations of PFAS research and (b) offer guidance for researchers and communications professionals who would like to publicize future work and increase its impact.