Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology.

Read-across (RAx) translates available information from well-characterized chemicals to a substance for which there is a toxicological data gap. The OECD is working on case studies to probe general applicability of RAx, and several regulations (e.g.

2-Hydroxyglutarate Metabolism Is Altered in an Model of LPS Induced Endotoxemia.

The metabolic response to endotoxemia closely mimics those seen in sepsis. Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration , and in human septic patients. We further show that enhanced activation of the enzymes responsible for 2-HG degradation, D- and L-2-HGDH, underlie this effect.

Defending victims of cyberbullying: The role of self-efficacy and moral disengagement.

Cyberbullying is a significant problem worldwide that affects adolescents' social relations, academic achievement, and mental health. As this form of bullying is typically viewed by a large audience it is important to understand the role of observers as they may hold a key for reducing bullying. The aim of this study was to investigate the role of the socio-cognitive factors of defending self-efficacy (i.

Identifying specific insomnia components in borderline personality disorder and their influence on emotion dysregulation.

Insomnia-related sleep problems are common in borderline personality disorder (BPD) and exacerbate the core of BPD, emotion dysregulation. Insomnia is elicited and maintained through behaviors that disrupt both the homeostatic and circadian sleep systems. However, it is unclear which homeostatic or circadian insomnia behaviors characterize BPD and exacerbate emotion dysregulation, thus warranting clinical attention in this population.

Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development.

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all.

Proposing a re-conceptualisation of competency framework terminology for health: a scoping review.

Background: Competency frameworks are being taken up by a growing number of sectors and for a broad range of applications. However, the topic of competency frameworks is characterised by conceptual ambiguity, misunderstanding and debate. Lack of consistency in the conceptualisation and use of key terminology creates a barrier to research and development, consensus, communication and collaboration, limiting the potential that competency frameworks have to deal with real workforce challenges.

Combining whole-school and targeted programs for the reduction of bullying victimization: A randomized, effectiveness trial.

Despite the extensive evaluation of school-based interventions for bullying, victimization remains a significant problem in schools. Bullying victimization is significantly predicted by contextual (school-related) factors. As a consequence whole-school programs have been commonly used to prevent and reduce bullying victimization.

The impact of trauma characteristics on post-traumatic stress disorder and substance use disorder outcomes across integrated and substance use treatments.

Proponents of complex post-traumatic stress disorder (PTSD) constructs suggest that specific trauma characteristics, such as earlier age of first trauma (trauma age) and higher number of traumas (trauma count), may obstruct PTSD symptom reduction in treatment. PTSD and substance use disorders (SUD) commonly co-occur, but the impact of trauma age and count on PTSD treatment responses in a comorbid PTSD and SUD sample is unclear. Further, no studies have examined the impact of trauma characteristics on SUD treatment outcomes or whether their impact on either PTSD or SUD outcomes varies if PTSD is directly addressed.

An evaluation framework for new approach methodologies (NAMs) for human health safety assessment.

The need to develop new tools and increase capacity to test pharmaceuticals and other chemicals for potential adverse impacts on human health and the environment is an active area of development. Much of this activity was sparked by two reports from the US National Research Council (NRC) of the National Academies of Sciences, Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007) and Science and Decisions: Advancing Risk Assessment (2009), both of which advocated for "science-informed decision-making" in the field of human health risk assessment. The response to these challenges for a "paradigm shift" toward using new approach methodologies (NAMS) for safety assessment has resulted in an explosion of initiatives by numerous organizations, but, for the most part, these have been carried out independently and are not coordinated in any meaningful way.

Reevaluating human colonization of the Caribbean using chronometric hygiene and Bayesian modeling.

Human settlement of the Caribbean represents the only example in the Americas of peoples colonizing islands that were not visible from surrounding mainland areas or other islands. Unfortunately, many interpretive models have relied on radiocarbon determinations that do not meet standard criteria for reporting because they lack critical information or sufficient provenience, often leading to specious interpretations. We have collated 2484 radiocarbon determinations, assigned them to classes based on chronometric hygiene criteria, and constructed Bayesian colonization models of the acceptable determinations to examine patterns of initial settlement.

Olmesartan-induced Enteropathy: A Rare Side Effect of a Common Medication.

Ischemic heart disease and stroke are the leading causes of mortality worldwide according to the World Health Organization. Hypertension is a major factor in the development of these diseases. Olmesartan is an angiotensin II receptor blocker (ARB) indicated in the treatment of hypertension.

Cadmium: Mitigation strategies to reduce dietary exposure.

Cadmium has long been recognized as an environmental contaminant that poses risks to human health. Cadmium is of concern since nearly everyone in the general population is exposed to the metal through the food supply and the ability of the element to accumulate in the body over a lifetime. In support of the United States Food and Drug Administration's (FDA) Toxic Element Working Group's efforts to reduce the risks associated with elements in food, this review sought to identify current or new mitigation efforts that have the potential to reduce exposures of cadmium throughout the food supply chain.

A review of the evidence to support interim reference level for dietary lead exposure in adults.

FDA developed the interim reference level (IRL) for lead of 3 μg/day in children and 12.5 μg/day in women of childbearing age (WOCBA) to better protect the fetus from lead toxicity. These IRLs correspond to a blood lead level (BLL) of 0.

Recent evolutionary history predicts population but not ecosystem-level patterns.

In the face of rapid anthropogenic environmental change, it is increasingly important to understand how ecological and evolutionary interactions affect the persistence of natural populations. Augmented gene flow has emerged as a potentially effective management strategy to counteract negative consequences of genetic drift and inbreeding depression in small and isolated populations. However, questions remain about the long-term impacts of augmented gene flow and whether changes in individual and population fitness are reflected in ecosystem structure, potentiating eco-evolutionary feedbacks.

Temporomandibular joint osteoarthritis at Chelechol ra Orrak, Palau.

Objective: To explore the frequency and severity of temporomandibular joint osteoarthritis (TMJ-OA) and its causative factors in a skeletal assemblage from the prehistoric site of Chelechol ra Orrak, Palau, western Micronesia.

Materials: 50 temporomandibular joint surfaces (mandibular condyles and articular eminences), representing a minimum of 22 adult individuals, 17 of which retain teeth.

Methods: Joint surfaces were macroscopically evaluated for characteristics associated with TMJ-OA and joint morphology.

Genomic and Fitness Consequences of Genetic Rescue in Wild Populations.

Gene flow is an enigmatic evolutionary force because it can limit adaptation but may also rescue small populations from inbreeding depression [1-3]. Several iconic examples of genetic rescue-increased population growth caused by gene flow [4, 5]-have reversed population declines [6, 7]. However, concerns about outbreeding depression and maladaptive gene flow limit the use of human-mediated gene flow in conservation [8, 9].

Oral Verruciform Xanthoma: A Series of 212 Cases and Review of the Literature.

Verruciform xanthoma (VX) of the oral cavity is an uncommon, reactive lesion of unknown etiology. In this study, we present a large series of VX with analysis of demographics, clinical appearance, histologic presentation and extensive review of literature. To the best of our knowledge, this is the largest series of oral VX reported to date.

The ACE Index: mapping childhood adversity in England.

Background: Studies of adults show that adverse childhood experiences (ACEs) are associated with health and social problems and are more common among people living in deprived areas. However, there is limited information about the geographical pattern of contemporary ACEs.

Methods: We used data from the police, social services, schools and vital statistics in England to calculate population rates of events that represent childhood adversity.