Synthetic vitreous fibers (SVFs): adverse outcome pathways (AOPs) and considerations for next generation new approach methods (NAMs).

Fiber dimension, durability/dissolution, and biopersistence are critical factors for the risk of fibrogenesis and carcinogenesis. In the modern era, to reduce, refine, and replace animals in toxicology research, the application of test methods is paramount for hazard evaluation and designing synthetic vitreous fibers (SVFs) for safe use. The objectives of this review are to: (1) summarize the international frameworks and acceptability criteria for implementation of new approach methods (NAMs), (2) evaluate the adverse outcome pathways (AOPs), key events (KEs), and key event relationships (KERs) for fiber-induced fibrogenesis and carcinogenesis in accordance with Organization for Economic Co-operation and Development (OECD) guidelines, (3) consider existing and emerging technologies for and toxicity testing for the respiratory system and the ability to predict effects , (4) outline a recommended testing strategy for evaluating the hazard and safety of novel SVFs, and (5) reflect on methods needs for correlation (IVIVC) and predictive approaches for safety assessment of new SVFs.

Postnatal Cardiometabolic Health After Metformin Use in Gestational Diabetes: A Secondary Analysis of the EMERGE Trial.

Aim: Women with GDM display adverse lifetime cardio-metabolic health. We examined whether early metformin in GDM could impact cardio-metabolic risk factors postpartum.

Research Design & Methods: EMERGE, a double-blind, placebo-controlled trial randomized pregnancies 1:1 to placebo or metformin at GDM diagnosis and followed participants from randomization until 12±4 weeks postpartum.

Risk characterization of N-nitrosodimethylamine in pharmaceuticals.

Since 2018, N-nitrosodimethylamine (NDMA) has been a reported contaminant in numerous pharmaceutical products. To guide the pharmaceutical industry, FDA identified an acceptable intake (AI) of 96 ng/day NDMA. The approach assumed a linear extrapolation from the Carcinogenic Potency Database (CPDB) harmonic-mean TD identified in chronic studies in rats.

Assessing potential human health and ecological implications of PFAS from leave-in dental products.

Contaminated water and food are the main sources of documented per- and polyfluoroalkyl substances (PFAS) exposure in humans. However, other sources may contribute to the overall PFAS intake. While several studies documented the presence of PFAS in consumer products, PFAS evaluation in dental products has been limited to floss and tape to date.

Evaluation of chemicals leached from PET and recycled PET containers into beverages.

The use of recycled polyethylene terephthalate (rPET) containers, a recent shift in the beverage industry, poses new potential human health concerns including contamination from the original container; use of additives, detergents, and catalysts during recycling; and improper recycling practices. The purpose of this analysis was to evaluate available data regarding: (1) chemicals leached from PET and rPET in bottle form; (2) concentration of these chemicals; and (3) trends between rPET percent and concentration of chemicals leached. This analysis identified 211 scientific articles related to recycled plastic and leachables.

Sanfilippo syndrome: consensus guidelines for clinical care.

Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care.

The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease.

Asthma is a generalized term that describes a scope of distinct pathologic phenotypes of variable severity, which share a common complication of reversible airflow obstruction. Asthma is estimated to affect almost 400 million people worldwide, and nearly ten percent of asthmatics have what is considered "severe" disease. The majority of moderate to severe asthmatics present with a "type 2-high" (T2-hi) phenotypic signature, which pathologically is driven by the type 2 cytokines Interleukin-(IL)-4, IL-5, and IL-13.

Genomic influences on self-reported childhood maltreatment.

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present.

The receptor for advanced glycation end products is a critical mediator of type 2 cytokine signaling in the lungs.

Background: Asthma is estimated to effect more than 300 million persons worldwide, leading to nearly 250,000 deaths annually. The majority of patients with mild-to-severe asthma have what is deemed "type-2 high" asthma, which is driven by the prototypical type 2 cytokines IL-4, IL-5, and IL-13. Studies have indicated that the receptor for advanced glycation end products (RAGE) is a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation.

Melphalan-Based Reduced-Intensity Conditioning is Associated with Favorable Disease Control and Acceptable Toxicities in Patients Older Than 70 with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope.

Endotoxin hitchhiking on polymer nanoparticles.

The control of microbial infections is critical for the preparation of biological media including water to prevent lethal septic shock. Sepsis is one of the leading causes of death in the United States. More than half a million patients suffer from sepsis every year.

The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome.

There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis.

Effect of contact angle on the orientation, stability, and assembly of dense floating cubes.

In this paper, the effect of contact angle, density, and size on the orientation, stability, and assembly of floating cubes was investigated. All the cubes tested were more dense than water. Floatation occurred as a result of capillary stresses induced by deformation of the air-water interface.

Safety and tolerability of fentanyl iontophoretic transdermal system: findings from a pooled data analysis of four clinical trials.

Acute postoperative pain remains inadequately managed. Although patient-controlled analgesia (PCA) represents a significant advance in postoperative pain management, drawbacks may include invasiveness and the potential for programming errors. The analysis presented here is based on pooled patient-level safety data from four multicenter, randomized, active-controlled trials that evaluated the safety and tolerability of the needle-free, preprogrammed fentanyl HCl iontophoretic transdermal system (ITS) versus morphine intravenous PCA for postoperative pzin management; the results for patients who received fentanyl ITS are presented here.

Firework injuries presenting to a national burn's unit.

The sale to the general public of fireworks is illegal in Ireland. However, many fireworks are readily available on the black market from illegal traders. The number of firework injuries presenting to our unit during the three week run-up to Hallowe'en October 2001 was recorded.

Clinical utility of plasma membrane vesicles expressing recombinant glycophorin A-encoded blood group antigens.

Background: Although the genes encoding most of the major blood group determinants are now cloned, recombinant blood group antigens are not commonly used in the clinical laboratory. This study assessed the feasibility of using plasma membrane vesicles expressing recombinant glycophorin A blood group antigens as soluble immunoadsorbants.

Study Design And Methods: Chinese hamster ovary cells were transfected with plasmids containing the cDNA encoding the M- or N-allele of glycophorin A.

Modeling the impact of prostate cancer early diagnosis on managed care plans.

Efforts to improve decisions about the appropriate use of new and existing technologies have prompted the development of technology assessment committees and advisory panels within managed care plans. As part of this development, plans are using a variety of sophisticated tools to aid their decision making. One such tool is the actuarial model, a method of quantitatively estimating the risk associated with providing care to specified populations.

K+ reabsorption by the lower Malpighian tubule of Rhodnius prolixus: inhibition by Ba2+ and blockers of H+/K+-ATPases.

Active K+ reabsorption by the lower Malpighian tubule of the blood-feeding hemipteran Rhodnius prolixus does not involve the amiloride-sensitive K+/H+ exchangers or V-type H+-ATPases implicated in secretion of ions from haemolymph to lumen in the upper tubule. Amiloride, N-ethylmaleimide, 4-chloro-7-nitrobenzo-2-oxa-1,3-diazol and bafilomycin A1 inhibit haemolymph-to-lumen secretion of Na+ and K+ by the upper Malpighian tubule, but have little or no effect on lumen-to-haemolymph reabsorption of K+ by the lower tubule. The effects of inhibitors of H+/K+-ATPases, including omeprazole and SCH 28080, suggest that a pump similar to the H+/K+-ATPase of the gastric mucosa is involved in KCl reabsorption.

Recombinant blood group antigens are useful for studying the fine specificity of antibodies against glycophorin A encoded antigens.

Recombinant wild-type and variant forms of glycophorin A (GPA) were expressed in wild-type and glycosylation-defective Chinese hamster ovary cells. The binding to recombinant GPA of antibodies submitted to the Third International Workshop was assessed by immunoprecipitation and indirect immunofluorescence. This is a powerful approach for determining the fine specificity of antibodies to blood group antigens.

Plasmodium falciparum merozoite adhesion is mediated by sialic acid.

The invasion of host red blood cells by Plasmodium falciparum merozoites is a complex process requiring multiple receptor-ligand interactions. Glycophorin A, a sialic acid-rich integral membrane protein, is an important RBC receptor for merozoites. We stably expressed glycophorin A in wild type Chinese hamster ovary (CHO) cells and in Lec 2 CHO cells which have a defect in the ability to sialylate proteins.

Excretion and distribution of ammonia and the influence of boundary layer acidification in embryonic rainbow trout (Oncorhynchus mykiss).

This study examined ammonia excretion by embryos of the rainbow trout (Oncorhynchus mykiss). The distribution of ammonia in relation to the H+ distribution and electrical potential was determined. The influence of the pH of the unstirred layer (USL) of water next to the external surface of the embryo was also assessed.

Preparation and characterization of fluorescein-labeled plasma membrane vesicles from transfected Chinese hamster ovary cells.

Plasma membrane vesicles have been used to study a wide variety of biological events including the nature of receptor-ligand interactions and the physiology of molecular transport across membranes. Plasma membrane vesicles were chemically induced from an adherent Chinese hamster ovary cell line expressing recombinant glycophorin A, a well-studied intrinsic membrane protein of the red blood cell. They were also prepared from Chinese hamster ovary cells in suspension culture.

EFFECTS OF AMMONIA LOADING ON PORCELLIO SCABER: GLUTAMINE AND GLUTAMATE SYNTHESIS, AMMONIA EXCRETION AND TOXICITY.

The effects of ammonia loading in the terrestrial isopod Porcellio scaber were studied by exposing animals to atmospheres of high PNH3. Isopods show a remarkable tolerance of elevated ambient PNH3, with an LD50 of 89 Pa for a 7-day exposure. However, haemolymph total ammonia concentrations generally remained below 5 mmol l-1 (PNH3=0.