Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies.

NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration

Practical psychosocial care for providers of pre-hospital care: a summary of the report 'valuing staff, valuing patients'.

BACKGROUND: Caring for people who are ill or injured in pre-hospital environments is emotionally draining and physically demanding. This article focuses on the Psychosocial and Mental Health Programme commissioned by the Faculty of Pre-Hospital Care (FPHC) at the Royal College of Surgeons of Edinburgh (RCSEd) in 2018 to investigate the experiences and needs of responders to pre-hospital emergencies and make recommendations. It summarises the report to FPHC published in 2022, and adds material from research published subsequently. METHOD: FPHC appointed a team to undertake the work. Team members conducted a literature review, and a systematic review of the literature concerning the impacts on the mental health of pre-hospital practitioners. They conducted fieldwork, participated in training and had conversations with trainees and established practitioners, and took evidence from the Pre-hospital Emergency Medicine Trainees Association (PHEMTA). RESULTS: The Results summarise the evidence-based theoretical background derived from the programme and practical guidance for practitioners, professional organisations, and employers who deliver pre-hospital care on the implications of, preventing and intervening with pre-hospital providers who experience psychosocial and mental health problems. CONCLUSION: This paper summarises the outputs from a multidisciplinary programme of scholarship, research, and fieldwork. The authors condense the findings and the guidance developed by the Programme Team to provide a summary of the report and guidance on implementation. They believe that the recommendations are applicable to all healthcare organisations and particularly those that employ responders to emergencies and provide pre-hospital care

Evidence of reproductive endocrine effects in women with occupational fuel and solvent exposures.

Hydrocarbons (HCs) found in fuels and solvents are ubiquitous in the environment, yet we know little about their effects on the endocrine system. The objective of this study was to assess the potential reproductive endocrine effects of low-dose HCs encountered by female U.S. Air Force personnel with fuel (primarily JP-8 jet fuel) and solvent exposures (n = 63). We estimated the internal dose of HCs in fuels and solvents by measuring their levels in exhaled breath, including the sum of aliphatic HCs (C6H14-C16H34) and the sum of aromatic HCs (benzene, ethylbenzene, toluene, and m,p,o-xylenes). Adverse outcome measures included urinary endocrine markers that have been associated with nonconceptive (vs. conceptive) menstrual cycles in ovulatory women: lower preovulatory luteinizing hormone (LH) and mid-luteal phase pregnanediol 3-glucuronide (Pd3G) and estrone 3-glucuronide, and higher follicle phase Pd3G. We also obtained reproductive and exposure information from baseline questionnaires and daily diaries. Toluene was the most frequently found analyte in the breath, with values up to 52.0 ppb, and benzene breath levels were up to 97.5 ppb. Regression analysis revealed that preovulatory LH levels were significantly lower (p = 0.007) among women whose total aliphatic HC levels were above the median. The relationship between elevated aliphatic HC exposure and lowered preovulatory LH levels in the present study suggests that compounds in fuels and some solvents may act as reproductive endocrine disruptors. Confirmation of these findings is needed, not only to determine if fuel and solvent exposure may impact other LH-dependent physiologic functions but also to examine effects of fuels and solvents on conception

Does Tribolium brevicornis Cuticular Chemistry Deter Cannibalism and Predation of Pupae?

The cuticular hydrocarbons of insects are species-specific and often function as semiochemicals. The activity of Tribolium brevicornis cuticular hydrocarbons as feeding deterrents that ostensibly function to prevent pupal cannibalism and predation was evaluated. The cuticular hydrocarbons of T. brevicornis pupae were characterized and flour disk bioassays conducted with individual and combined extract components incorporated into artificial diets on which Tribolium adults fed for six days. Feeding by T. brevicornis and T. castaneum on flour disks containing cuticular extracts of T. brevicornis pupae resulted in reduced consumption and weight loss relative to feeding on control flour disks. In both cases, feeding deterrence indices exceeded 80% suggesting that T. brevicornis cuticular hydrocarbons could function to deter cannibalism and predation of pupae by larvae and adult beetles. Sixteen different cuticular hydrocarbons were identified in T. brevicornis pupal extracts. Eight of the commercially available linear alkanes were tested individually in feeding trials with eight Tribolium species. One compound (C28) significantly reduced the amount of food consumed by three species compared to control disks, whereas the compounds C25, C26, and C27 elicited increased feeding in some species. Four other compounds had no effect on consumption for any species. When four hydrocarbon mixtures were tested for synergistic deterrence on T. brevicornis and T. castaneum, none significantly influenced consumption. Our results indicate that the cuticular chemistry of T. brevicornis pupae could serve to deter predation by conspecific and congeneric beetles

High Performance Ebis for Rhic.

An Electron Beam Ion Source (EBIS), capable of producing high charge states and high beam currents of any heavy ion species in short pulses, is ideally suited for injection into a synchrotron. An EBIS-based, high current, heavy ion preinjector is now being built at Brookhaven to provide increased capabilities for the Relativistic Heavy Ion Collider (RHIC), and the NASA Space Radiation Laboratory (NSRL). Benefits of the new preinjector include the ability to produce ions of any species, fast switching between species to serve the simultaneous needs of multiple programs, and lower operating and maintenance costs. A state-of-the-art EBIS, operating with an electron beam current of up to 10 A, and producing multi-milliamperes of high charge state heavy ions, has been developed at Brookhaven, and has been operating very successfully on a test bench for several years. The present performance of this high-current EBIS is presented, along with details of the design of the scaled-up EBIS for RHIC, and the status of its construction. Other aspects of the project, including design and construction of the heavy ion RFQ, Linac, and matching beamlines, are also mentioned

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Adult fly age estimations using cuticular hydrocarbons and Artificial Neural Networks in forensically important Calliphoridae species

Blowflies (Diptera: Calliphoridae) are forensically important as they are known to be one of the first to colonise human remains. The larval stage is typically used to assist a forensic entomologists with adult flies rarely used as they are difficult to age because they remain morphologically similar once they have gone through the initial transformation upon hatching. However, being able to age them is of interest and importance within the field. This study examined the cuticular hydrocarbons (CHC) of Diptera: Calliphoridae species Lucilia sericata, Calliphora vicina and Calliphora vomitoria. The CHCs were extracted from the cuticles of adult flies and analysed using Gas Chromatography–Mass Spectrometry (GC–MS). The chemical profiles were examined for the two Calliphora species at intervals of day 1, 5, 10, 20 and 30 and up to day 10 for L. sericata. The results show significant chemical changes occurring between the immature and mature adult flies over the extraction period examined in this study. With the aid of a Principal Component Analysis (PCA) and Artificial Neural Networks (ANN), samples were seen to cluster, allowing for the age to be established within the aforementioned time frames. The use of ANNs allowed for the automatic classification of novel samples with very good performance. This was a proof of concept study, which developed a method allowing to age post-emergence adults by using their chemical profiles

Over 675,000 lay people trained in cardiopulmonary resuscitation worldwide - The "World Restart a Heart (WRAH)" initiative 2018

Non peer reviewe

A high-performance electron beam ion source

At Brookhaven National Laboratory, a high current Electron Beam Ion Source (EBIS) has been developed as part of a new preinjector that is under construction to replace the Tandem Van de Graaffs as the heavy ion preinjector for the RHIC and NASA experimental programs. This preinjector will produce milliampere-level currents of essentially any ion species, with q/A {ge} 1/6, in short pulses, for injection into the Booster synchrotron. In order to produce the required intensities, this EBIS uses a 10A electron gun, and an electron collector designed to handle 300 kW of pulsed electron beam power. The EBIS trap region is 1.5 m long, inside a 5T, 2m long, 8-inch bore superconducting solenoid. The source is designed to switch ion species on a pulse-to-pulse basis, at a 5 Hz repetition rate. Singly-charged ions of the appropriate species, produced external to the EBIS, are injected into the trap and confined until the desired charge state is reached via stepwise ionization by the electron beam. Ions are then extracted and matched into an RFQ, followed by a short IH Linac, for acceleration to 2 MeV/A, prior to injection into the Booster synchrotron. An overview of the preinjector is presented, along with experimental results from the prototype EBIS, where all essential requirements have already been demonstrated. Design features and status of construction of the final high intensity EBIS is also be presented