The chemical landscape: the future of risk assessment toward optimum consumer safety.

The further optimization of consumer safety through risk assessment of chemicals present in food will require adaptability and flexibility to utilize the accelerating developments in safety science and technology. New Approach Methodologies (NAMs) are gaining traction as a systematic approach to support informed decision making in chemical risk assessment. The vision is to be able to predict risk more accurately, rapidly and efficiently.

Screening patients for unintentional carbon monoxide exposure in the Emergency Department: a cross-sectional multi-centre study.

Background: Low-level exposure to carbon monoxide (CO) is a significant health concern but is difficult to diagnose. This main study aim was to establish the prevalence of low-level CO poisoning in Emergency Department (ED) patients.

Methods: A prospective cross-sectional study of patients with symptoms of CO exposure was conducted in four UK EDs between December 2018 and March 2020.

Tumours modulate the systemic vascular response to anti-angiogenic therapy.

Toxicologic evaluation of new drug candidates routinely utilizes healthy animals. In oncology, there remains a limited understanding of the effects of novel test candidates in a diseased host. For vascular modulating agents (VMAs), an increased understanding of preclinical tumour-host interaction, and its potential to exacerbate or alleviate 'off-target' effects of anti-angiogenic administration, could aid in the prediction of adverse clinical outcomes in a defined cancer patient.

Tumors modulate fenestrated vascular beds and host endocrine status.

Allograft and xenograft transplantation into a mouse host is frequently utilized to study cancer biology, tumor behavior, and response to treatment. Preclinical studies employing these models often focus solely upon the intra-tumoral effects of a given treatment, without consideration of systemic toxicity or tumor-host interaction, nor whether this latter relationship could modulate the toxicologic response to therapy. Here it is demonstrated that the implantation and growth of a range of human- and mouse-derived cell lines leads to structural vascular and, potentially, functional changes within peripheral endocrine tissues, a process that could conceivably ameliorate the severity of anti-angiogenic-induced fenestrated vessel attenuation.

Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur Mustard, Soman and VX.

Background/aims: Following an incident involving toxic chemicals, deployment of countermeasures before the arrival of specialised services at the scene may provide a "therapeutic" window in which to mitigate skin absorption.

Methods: Five potential candidates (itaconic acid, N,N'-methylenebisacrylamide, 2-trifluoromethylacrylic acid, fuller's earth and Fast-Act®) previously found effective against a simulant (methyl salicylate) were evaluated against a 10 μL droplet of C-sulphur mustard (HD), soman (GD) or VX applied to the surface of porcine skin mounted on static skin diffusion cells.

Results: All the decontaminants applied to the skin 5 min post exposure achieved a marked reduction in the amount of C contaminant remaining within the skin at 24 h.

Automated image analysis of intra-tumoral and peripheral endocrine organ vascular bed regression using 'Fibrelength' as a novel structural biomarker.

The study of vascular modulation has received a great deal of attention in recent years as knowledge has increased around the role of angiogenesis within disease contexts such as cancer. Despite rapidly expanding insights into the molecular processes involved and the concomitant generation of a number of anticancer vascular modulating chemotherapeutics, techniques used in the measurement of structural vascular change have advanced more modestly, particularly with regard to the preclinical quantification of off-target vascular regression within systemic, notably endocrine, blood vessels. Such changes translate into a number of major clinical side effects and there remains a need for improved preclinical screening and analysis.

Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate).

Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers.

Arm elevation and coordinated breathing strategies in patients with COPD.

Background: Hyperinflated patients with COPD breathe against an increased elastic load during physical activity. Arm activities are especially demanding. Some pulmonary rehabilitation programs instruct patients to inhale while raising their arms, whereas others recommend the opposite.

European initiative towards quality standards in education and training for discovery, development and use of medicines.

This position paper recommends a set of standards for quality assessment of continuing professional development (CPD) for medicines research and development (R&D). We have developed these standards to help us achieve the education and training goals of the Innovative Medicines Initiative (IMI; www.imi.

Comparative analysis of showering protocols for mass-casualty decontamination.

A well-established provision for mass-casualty decontamination that incorporates the use of mobile showering units has been developed in the UK. The effectiveness of such decontamination procedures will be critical in minimizing or preventing the contamination of emergency responders and hospital infrastructure. The purpose of this study was to evaluate three empirical strategies designed to optimize existing decontamination procedures: (1) instructions in the form of a pictorial aid prior to decontamination; (2) provision of a washcloth within the showering facility; and (3) an extended showering period.

Role of mitochondria in drug-induced cholestatic injury.

Mitochondria have multiple functions in eukaryotic cells and are organized into dynamic tubular networks that continuously undergo changes through coordinated fusion and fission and migration through the cytosol. Mitochondria integrate cell-signaling networks, especially those involving the intracellular messenger Ca(2+), into the regulation of metabolic pathways. Recently, it has become clear that mitochondria are central to the three main cell death pathways, namely necrosis, apoptosis, and autophagic cell death.

Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c, Bax, Bid, and caspases.

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid).