Is there any added value of the second generation in the Extended One-Generation Reproductive Toxicity Study (EOGRTS)? A retrospective analysis of 24 EOGRTS.

The Extended One-Generation Reproductive Toxicity Study (EOGRTS) is a standard information requirement under Registration, Evaluation, Authorization and restriction of Chemicals (REACH) in Europe. Inclusion of an F2 generation is considered useful if this impacts hazard identification or when it provides additional information altering the reproductive or developmental No Observed Adverse Effect Level (NOAEL) and subsequent risk assessment. In this retrospective analysis the added value of the F2 generation in 24 EOGRTS was evaluated.

Review of dose setting for the extended one-generation reproductive toxicity studies (OECD TG 443): Considerations on ECHA's dose level selection recommendations.

During 2020, The European Chemicals Agency (ECHA) began evaluating the OECD Test Guideline 443: Extended One Generation Reproductive Toxicity Study (EOGRTS) to analyze specific aspects related to study design, conduct and toxicological findings. A significant outcome of this ECHA evaluation focused on adequate dose level selection. Subsequently, ECHA published recommendations for DART studies, however, these recommendations seemingly do not align with the principles of the 3Rs, animal welfare or human safety goals, specifically, regarding three aspects.

EVIDENCE OF PROTOZOAN AND BACTERIAL INFECTION AND CO-INFECTION AND PARTIAL BLOOD FEEDING IN THE INVASIVE TICK HAEMAPHYSALIS LONGICORNIS IN PENNSYLVANIA.

The Asian longhorned tick, Haemaphysalis longicornis, an invasive tick species in the United States, has been found actively host-seeking while infected with several human pathogens. Recent work has recovered large numbers of partially engorged, host-seeking H. longicornis, which together with infection findings raises the question of whether such ticks can reattach to a host and transmit pathogens while taking additional bloodmeals.

Monitoring Respiratory Motion With Wi-Fi CSI: Characterizing Performance and the BreatheSmart Algorithm.

Respiratory motion (i.e., motion pattern and rate) can provide valuable information for many medical situations.

Building Research Infrastructure: The Development of a Technical Assistance Group-Service Center at an RCMI.

As one of the Research Centers for Minority Institutions (RCMI), the Southwest Health Equity Research Collaborative (SHERC) worked over the first five-year period of funding to foster the advancement of Early Stage Investigators, enhance the quality of health disparities research, and increase institution research capacity in basic Biomedical, Behavioral, and/or Clinical research; all priorities of RCMIs. In year 4, the Technical Assistance Group-Service Center (TAG-SC) was created to help achieve these goals. The TAG-SC provides one-on-one investigator project development support, including research design, data capture, and analysis.

Lack of direct bone effect of tofacitinib, a JAK inhibitor, in juvenile rats and evaluation of the association between offspring growth and femur length.

Bone has recently emerged as a target organ for some Janus kinase (JAK) inhibitors in adult and/or juvenile animal toxicity studies. Oral administration of tofacitinib, a JAK inhibitor, was not associated with clinical or macroscopic effects on bone growth and development in a rat juvenile animal study (JAS) with tofacitinib dosing starting on postnatal day (PND) 21. However, given that previous JAS did not include a targeted evaluation of bone, inclusive of microscopic examination, an additional rat JAS was conducted to further assess this risk.

Borrelia burgdorferi Sensu Stricto DNA in Field-Collected Haemaphysalis longicornis Ticks, Pennsylvania, United States.

We collected questing Haemaphysalis longicornis ticks from southeastern counties of Pennsylvania, USA. Of 263 ticks tested by PCR for pathogens, 1 adult female was positive for Borrelia burgdorferi sensu stricto, yielding a 0.4% infection rate.

A Case Study of Medical Device Wireless Coexistence Evaluation.

This article aims to provide a narrative for addressing wireless coexistence in medical devices to help medical device developers, test engineers, and regulatory affairs personnel throughout the device life cycle. Accordingly, we present a case-study covering the coexistence evaluation process including the risk analysis of the wireless functionality of a hypothetical medical device, determining the corresponding risk category, specification of the device functional wireless performance (FWP), wireless coexistence testing, and measurement of the intended/untended signal ratio. Also, we propose a simple method for translating the test outcome into user recommendations for minimum/maximum separation distances between the device, its intended companion, and the source of unintended signals.

Trichloroethylene in drinking water throughout gestation did not produce congenital heart defects in Sprague Dawley rats.

Background: Trichloroethylene (TCE) was negative for developmental toxicity after inhalation and oral gavage exposure of pregnant rats but fetal cardiac defects were reported following drinking water exposure throughout gestation. Because of the deficiencies in this latter study, we performed another drinking water study to evaluate whether TCE causes heart defects.

Methods: Groups of 25 mated Sprague Dawley rats consumed water containing 0, 0.

Practical considerations for developmental thyroid toxicity assessments: What's working, what's not, and how can we do better?

Thyroid hormones (THs; T3 and T4) play a role in development of cardiovascular, reproductive, immune and nervous systems. Thus, interpretation of TH changes from rodent studies (during pregnancy, in fetuses, neonates, and adults) is critical in hazard characterization and risk assessment. A roundtable session at the 2017 Society of Toxicology (SOT) meeting brought together academic, industry and government scientists to share knowledge and different perspectives on technical and data interpretation issues.

Report from the BfR expert hearing on practicability of hormonal measurements: recommendations for experimental design of toxicological studies with integrated hormonal end points.

This publication summarizes discussions that were held during an international expert hearing organized by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany, in October 2017. The expert hearing was dedicated to providing practical guidance for the measurement of circulating hormones in regulatory toxicology studies. Adequate measurements of circulating hormones have become more important given the regulatory requirement to assess the potential for endocrine disrupting properties for all substances covered by the plant protection products and biocidal products regulations in the European Union (EU).

Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer.

CCR8 is a chemokine receptor expressed principally on regulatory T cells (Treg) and is known to be critical for CCR8 Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of patients with breast, colon, and lung cancer when compared with normal tissue-resident Tregs. Therefore, CCR8 tumor-resident Tregs are rational targets for cancer immunotherapy.

Reproductive and developmental toxicity of potassium perfluorohexanesulfonate in CD-1 mice.

Potassium perfluorohexanesulfonate (KPFHxS) was evaluated for reproductive/developmental toxicity in CD-1 mice. Up to 3 mg/kg-d KPFHxS was administered (n = 30/sex/group) before mating, for at least 42 days in F males, and for F females, through gestation and lactation. F pups were directly dosed with KPFHxS for 14 days after weaning.

Rethinking developmental toxicity testing: Evolution or revolution?

Background: Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental toxicity testing?

Methods: A workshop was held under the auspices of the Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute to consider how we might design developmental toxicity testing if we started over with 21st century knowledge and techniques (revolution). We first consider what changes to the current protocols might be recommended to make them more predictive for human risk (evolution).

Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice.

FoxN1 is cell-autonomously expressed in skin and thymic epithelial cells (TECs), essential for their development. Inborn mutation of FoxN1 results in hair follicle and TEC development failure, whereas insufficient postnatal FoxN1 expression induces thymic atrophy, resulting in declined T lymphopoiesis. Although upregulating FoxN1 expression in the aged FoxN1-declined thymus rejuvenates T lymphopoiesis, whether its over- and ectopic-expression in early life is beneficial for T lymphopoiesis is unknown.

Placental transfer of (125)Iodinated humanized immunoglobulin G2Δa in the Sprague Dawley rat.

Antibody-like biopharmaceuticals cross the placenta by utilizing transport pathways available for transfer of maternal antibodies to the conceptus. To characterize the timing and magnitude of this transfer in the rat, embryo/fetal biodistribution of maternally administered radiolabeled humanized IgG2 was quantified over the course of gestation using gamma counting and whole body autoradiography. The result was humanized IgG2 found in rat embryo/fetal tissues as early as gestation day 11 with a >1000-fold increase in the amount of total IgG2 by day 21.

Leidenfrost levitation: beyond droplets.

Friction is a major inhibitor in almost every mechanical system. Enlightened by the Leidenfrost effect - a droplet can be levitated by its own vapor layer on a sufficiently hot surface - we demonstrate for the first time that a small cart can also be levitated by Leidenfrost vapor. The levitated cart can carry certain amount of load and move frictionlessly over the hot surface.

Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis.

Mutation in the "nude" gene, i.e. the FoxN1 gene, induces a hairless phenotype and a rudimentary thymus gland in mice (nude mouse) and humans (T-cell related primary immunodeficiency).

Identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice.

Gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. As the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γHV68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. We report here the genome sequence and characterization of a novel rodent gammaherpesvirus, designated rodent herpesvirus Peru (RHVP), that shares conserved genes and genome organization with γHV68 and the primate gammaherpesviruses but is phylogenetically distinct from γHV68.

Gait-specific energetics contributes to economical walking and running in emus and ostriches.

A widely held assumption is that metabolic rate (Ė(met)) during legged locomotion is linked to the mechanics of different gaits and this linkage helps explain the preferred speeds of animals in nature. However, despite several prominent exceptions, Ė(met) of walking and running vertebrates has been nearly uniformly characterized as increasing linearly with speed across all gaits. This description of locomotor energetics does not predict energetically optimal speeds for minimal cost of transport (E(cot)).

Severity of unhealthy alcohol consumption in medical inpatients and the general population: is the general hospital a suitable place for brief interventions?

Objectives: Evidence for brief interventions in general hospital (GH) settings is scarce, probably due to higher rates of dependent drinkers. The present study aims to compare unhealthy drinking patterns in GH patients with the general population (GP).

Methods: Sample 1 consisted of 4,075 individuals randomly drawn from registration office files, representing the non-institutionalised GP of a northern mixed rural-urban German area.

Latent herpesvirus infection arms NK cells.

Natural killer (NK) cells were identified by their ability to kill target cells without previous sensitization. However, without an antecedent "arming" event, NK cells can recognize, but are not equipped to kill, target cells. How NK cells become armed in vivo in healthy hosts is unclear.

At-risk and heavy episodic drinking, motivation to change, and the development of alcohol dependence among men.

Objective: The purpose of this study was to analyze whether general hospital inpatients with at-risk and heavy episodic drinking (ARHE) have a higher motivation to change drinking habits and a higher risk of developing alcohol dependence than individuals with at-risk drinking only (AR) or heavy episodic drinking only (HE).

Method: A proactively recruited sample of 425 male general hospital inpatients with AR, HE, or ARHE was used. Men with current alcohol dependence or abuse were excluded.