Determination of Cyanide Exposure by Gas Chromatography–mass Spectrometry Analysis of Cyanide-exposed Plasma Proteins

Exposure to cyanide can occur in a variety of ways, including exposure to smoke from cigarettes or fires, accidental exposure during industrial processes, and exposure from the use of cyanide as a poison or chemical warfare agent. Confirmation of cyanide exposure is difficult because, in vivo, cyanide quickly breaks down by a number of pathways, including the formation of both free and protein-bound thiocyanate. A simple method was developed to confirm cyanide exposure by extraction of protein-bound thiocyanate moieties from cyanide-exposed plasma proteins. Thiocyanate was successfully extracted and subsequently derivatized with pentafluorobenzyl bromide for GC–MS analysis. Thiocyanate levels as low as 2.5 ng mL−1 and cyanide exposure levels as low as 175 g kg−1 were detected. Samples analyzed from smokers and non-smokers using this method showed significantly different levels of protein-bound thiocyanate (p \u3c 0.01). These results demonstrate the potential of this method to positively confirm chronic cyanide exposure through the analysis of protein-bound cyanide in human plasma

Anthropometric profiles of elite athletes

Quantifying body composition is central to monitoring performance and training in athletes, however limited sport-specific anthropometric reference data, assessed and reported in a standardised manner, is available. This study provides anthropometric profiles in elite male athletes from different sports. Elite male athletes (n = 73) from National squads of boxing (n = 10), cricket (n = 21), swimming (n = 23), hockey (n = 10) and eventing (n = 9) were assessed for body mass, height, eight skinfolds (triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, thigh and medial calf), body circumferences (arm, waist, hip, thigh and calf) and muscle circumferences (arm, thigh, calf) using ISAK standardised guidelines. For all athletes, large variability exists for measures of skinfold thickness at each skinfold site. Swimming (64.6 ± 16.1 mm) and boxing (63.5 ± 16.1 mm) were similar for the sum of eight skinfolds (Σ8SKF) but swimming had lower Σ8SKF compared to cricket (86.1 ± 21.3 mm; p = .011) and eventing (89.9 ± 30.7 mm; p = .028). Hockey (81.9 ± 26.3 mm) and eventing had the most varied Σ8SKF. Thigh body (p=.006) and muscle circumferences (p = .005) were significantly reduced in boxing compared to hockey. No differences were seen between sports for arm (p = .346; ES = .06) and calf (p = .382; ES = .06) muscle circumferences. The anthropometric profiles for elite athletes from various sports during pre-season training will be a useful resource for sports professionals when monitoring and interpreting body composition data. Large variation exists in anthropometric profiles between the different athletes and different sports, highlighting the necessity to have sport-specific normative ranges available to allow optimal monitoring of individual athletes particularly varying across sports as well as age, training status and position

Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing

Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources

Investigating the clinical use of structured light plethysmography to assess lung function in children with neuromuscular disorders

BackgroundChildren and young people with neuromuscular disorders (NMD), such as Duchenne Muscular Dystrophy (DMD), develop progressive respiratory muscles weakness and pulmonary restriction. Pulmonary function monitoring of the decline in lung function allows for timely intervention with cough assist techniques and nocturnal non-invasive ventilation (NIV). NMD may find the measurement of lung function difficult using current techniques. Structured Light Plethysmography (SLP) has been proposed as a novel, non-contact, self-calibrating, non-invasive method of assessing lung function. The overarching aim of this study was to investigate the use of SLP as a novel method for monitoring respiratory function in children with neuromuscular disease.MethodsSLP thoraco-abdominal (TA) displacement was correlated with forced vital capacity measurements recorded by spirometry and the repeatability of the measurements with both methods examined. SLP tidal breathing parameters were investigated to assess the range and repeatability of regional right and left side TA displacement and rib cage and abdominal wall displacement.ResultsThe comparison of the FVC measured with SLP and with spirometry, while having good correlation (R = 0.78) had poor measurement agreement (95% limits of agreement: -1.2 to 1.2L) The mean relative contribution of right and left TA displacement in healthy controls was 50:50 with a narrow range. Repeatability of this measure with SLP was found to be good in healthy controls and moderate in NMD children with/without scoliosis but with a wider range. The majority of the control group displayed a predominant rib cage displacement during tidal breathing and those who displayed predominant abdominal wall displacement showed displacement of both regions close to 50:50 with similar results for the rib cage and abdomen. In comparison, children with NMD have a more variable contribution for all of these parameters. In addition, SLP was able to detect a reduction in abdominal contribution to TA displacement with age in the DMD group and detect paradoxical breathing in children with NMD. Using SLP tracings during tidal breathing we were able to identify three specific patterns of breathing amongst healthy individuals and in children with NMD.ConclusionsSLP is a novel method for measuring lung function that requires limited patient cooperation and may be especially useful in children with neuromuscular disorders. Measuring the relative contributions of the right and left chest wall and chest versus abdominal movements allows a more detailed assessment

tert-Butyl 2-(4-chloro­benzo­yl)-2-methyl­propanoate

The title compound, C15H19ClO3, is bent with a dihedral angle of 72.02 (9)° between the mean planes of the benzene ring and a group encompassing the ester functionality (O=C—O—C). In the crystal, mol­ecules related by inversion symmetry are connected by weak C—H⋯O inter­actions into infinite chains. These inter­actions involve H atoms from a methyl group of the dimethyl residue and the O atoms of the ketone on one side of a mol­ecule; on the other side there are inter­actions between H atoms of the benzene ring and the carbonyl O atoms of the ester functionality. There are no directional inter­actions between the chains

Gravitational waves: search results, data analysis and parameter estimation

The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity

Inhibition of IRE1 alpha RNase activity reduces NLRP3 inflammasome assembly and processing of pro-IL1 beta

The inflammasome is a multiprotein complex assembled in response to Pathogen Associated Molecular Patterns (PAMPs) and Danger Associated Molecular Patterns (DAMPS). Inflammasome activation occurs through a two-step mechanism, with the first signal facilitating priming of inflammasome components while the second signal triggers complex assembly. Once assembled, the inflammasome recruits and activates pro-caspase-1, which in turn processes pro-interleukin (IL)-18 and pro-IL-1 beta into their bio-active forms. Owing to its key role in the regulation of innate immune responses, the inflammasome has emerged as a therapeutic target for the treatment of inflammatory conditions. In this study we demonstrate that IRE1 alpha, a key component of the Unfolded Protein Response, contributes to assembly of the NLRP3 inflammasome. Blockade of IRE1 alpha RNase signaling lowered NLRP3 inflammasome assembly, caspase-1 activation and pro-IL-1 beta processing. These results underscore both the importance and potential therapeutic relevance of targeting IRE1 alpha signaling in conditions of excessive inflammasome formation