Incidence of adverse respiratory events after adjustment of clear fluid fasting recommendations to 1 h: a prospective, observational, multi-institutional cohort study.

BACKGROUND: Preoperative fasting reduces the risk of pulmonary aspiration during anaesthesia, and 2-h fasting for clear fluids has commonly been recommended. Based on recent evidence of shorter fasting times being safe, the Swiss Society of Paediatric Anaesthesia began recommending 1-h fasting for clear fluids in 2018. This prospective, observational, multi-institutional cohort study aimed to investigate the incidence of adverse respiratory events after implementing the new national recommendation. METHODS: Eleven Swiss anaesthesia institutions joined this cohort study and included patients aged 0-15 yr undergoing anaesthesia for elective procedures after implementation of the 1-h fasting instruction. The primary outcome was the perioperative (defined as the time from anaesthesia induction to emergence) incidence of pulmonary aspiration, gastric regurgitation, and vomiting. Data are presented as median (inter-quartile range; minimum-maximum) or count (percentage). RESULTS: From June 2019 to July 2021, 22 766 anaesthetics were recorded with pulmonary aspiration occurring in 25 (0.11%), gastric regurgitation in 34 (0.15%), and vomiting in 85 (0.37%) cases. No major morbidity or mortality was associated with pulmonary aspiration. Subgroup analysis by effective fasting times (<2 h [n=7306] vs ≥2 h [n=14 660]) showed no significant difference for pulmonary aspiration between these two groups (9 [0.12%] vs 16 [0.11%], P=0.678). Median effective fasting time for clear fluids was 157 [104-314; 2-2385] min. CONCLUSIONS: Implementing a national recommendation of 1-h clear fluid fasting was not associated with a higher incidence of pulmonary aspiration compared with previously reported data.

Pre-operative fasting in children: A guideline from the European Society of Anaesthesiology and Intensive Care.

Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents. We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force. Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a 'light breakfast' may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying.

Improved distributed Δ -coloring.

We present a randomized distributed algorithm that computes a Δ -coloring in any non-complete graph with maximum degree Δ ≥ 4 in O ( log Δ ) + 2 O ( log log n ) rounds, as well as a randomized algorithm that computes a Δ -coloring in O ( ( log log n ) 2 ) rounds when Δ ∈ [ 3 , O ( 1 ) ] . Both these algorithms improve on an O ( log 3 n / log Δ ) -round algorithm of Panconesi and Srinivasan (STOC'93), which has remained the state of the art for the past 25 years. Moreover, the latter algorithm gets (exponentially) closer to an Ω ( log log n ) round lower bound of Brandt et al. (STOC'16).

E-commerce trade in invasive plants.

Biological invasions are a major concern in conservation, especially because global transport of species is still increasing rapidly. Conservationists hope to anticipate and thus prevent future invasions by identifying and regulating potentially invasive species through species risk assessments and international trade regulations. Among many introduction pathways of non-native species, horticulture is a particularly important driver of plant invasions. In recent decades, the horticultural industry expanded globally and changed structurally through the emergence of new distribution channels, including internet trade (e-commerce). Using an automated search algorithm, we surveyed, on a daily basis, e-commerce trade on 10 major online auction sites (including eBay) of approximately three-fifths of the world's spermatophyte flora. Many recognized invasive plant species (>500 species) (i.e., species associated with ecological or socio-economic problems) were traded daily worldwide on the internet. A markedly higher proportion of invasive than non-invasive species were available online. Typically, for a particular plant family, 30-80% of recognized invasive species were detected on an auction site, but only a few percentages of all species in the plant family were detected on a site. Families that were more traded had a higher proportion of invasive species than families that were less traded. For woody species, there was a significant positive relationship between the number of regions where a species was sold and the number of regions where it was invasive. Our results indicate that biosecurity is not effectively regulating online plant trade. In the future, automated monitoring of e-commerce may help prevent the spread of invasive species, provide information on emerging trade connectivity across national borders, and be used in horizon scanning exercises for early detection of new species and their geographic source areas in international trade.

Acute hypoxic hypoxia and isocapnic hypoxia effects on oculometric features.

INTRODUCTION: Visual performance impairment after hypoxia is well recognized in military and civilian aviation. The aims of this study were: 1) to assess oculometric features such as blink metrics, pupillary dynamics, fixations, and saccades as cognitive indicators of early signs of hypoxia; and 2) to analyze the impact of different hypoxic conditions ["hypoxic hypoxia" (HH) and "isocapnic hypoxia" (IH)] on specified oculometrics during mental workloads. METHODS: Oculometric data were collected on 25 subjects under 3 conditions: normoxia, HH (8% O2 + balance N2), and IH (7% O2 + 5% CO2 + balance N2). The mental workload task consisted of reading aloud linear arrays of numbers after exposure to gas mixtures. RESULTS: Blink rates were significantly increased under hypoxic conditions (by +100.7% in HH and by +92.8% in IH compared to normoxia). A faster recovery of blink rate was observed in transitioning from IH (23.6% vs. 76.3%) to normoxia. The percentage change in pupil size fluctuation was increased under HH more than under IH (29% vs. 4.4%). Under HH average fixation time and target area size were significantly higher than under IH. Total saccadic times under hypoxic conditions were significantly increased compared with normoxia. CONCLUSIONS: These results suggest that oculometric changes are indicators of hypoxia, which can be monitored using compact, portable, noninvasive eye-tracking devices in a cockpit analogous environment to detect hypoxia-induced physiological changes in aircrew. Comparative results between HH and IH support the potential role of carbon dioxide in augmenting cerebral perfusion and hence improved tissue oxygen delivery.

Early detection of hypoxia-lnduced cognitive impairment using the King-Devick test.

INTRODUCTION: Hypoxic incapacitation continues to be a significant threat to safety and operations at high altitude. Noninvasive neurocognitive performance testing is desirable to identify presymptomatic cognitive impairment, affording operators at altitude a tool to quantify their performance and safety. METHODS: There were 25 subjects enrolled in this study. Cognitive performance was assessed by using the King-Devick (K-D) test. The performance of the subjects on the K-D test was measured in normoxia followed by hypoxia (8% 02 equivalent to 7101 m) and then again in normoxia. RESULTS: K-D test completion time in hypoxia for 3 min was significantly longer than the Baseline Test (54.5 +/- 12.4 s hypoxic vs. 46.3 +/- 10.4 s baseline). Upon returning to normoxia the completion time was significantly shorter than in hypoxia (47.6 +/- 10.6 s post test vs. 54.5 +/- 12.4 s hypoxic). There was no statistically significant difference between baseline test and post test times, indicating that all subjects returned to their normoxic baseline levels. SpO2 decreased from 98 +/- 0.9% to 80 +/- 7.8% after 3 min on hypoxic gas. During the hypoxic K-D test, SpO2 decreased further to 75.8 +/- 8.3%. CONCLUSIONS: In this study the K-D test has been shown to be an effective neurocognitive test to detect hypoxic impairment at early presymptomatic stages. The K-D test may also be used to afford a reassessment of traditional measures used to determine hypoxic reserve time.

One-year evolution of ulnar somatosensory potentials after trauma in 365 tetraplegic patients: early prediction of potential upper limb function.

Early prediction of hand function is crucial for efficient rehabilitation of cervical spinal cord injury (cSCI). This study investigated correlations between ulnar somatosensory evoked potentials (ulnar SSEPs) and functional outcome of hand function following acute traumatic cervical cord injury. Neurological assessment of sensory scores and hand function were compared with five ulnar SSEP categories of similar persistence and quality in 365 patients throughout the first year after cSCI. Of the 365 patients, 218 (68%) exhibited ulnar SSEP potentials at any one stage during the year, and in 147 patients (40.3%) ulnar SSEPs were obtainable at every assessment stage. While ulnar SSEP latency and amplitude assessments remained largely unchanged over time in the majority of patients, hand function improved remarkably during the first year following cSCI. One year outcome of hand function was predetermined by ulnar SSEP category due to distinct differences in the ulnar SSEP parameters. Additionally, an early prognostic group allocation by ulnar SSEP criteria at the first assessment stage within 4 weeks after spinal trauma allowed reliable prediction of hand function outcome after 1 year. We conclude that early assessment of ulnar SSEP as a non-invasive and objective neurophysiological test is a valuable marker of prospective hand function and independence 1 year after cSCI. This could be most relevant for planning neurorehabilitation, and in prospective clinical SCI trials.

Chemical basis for the extreme skin sensitization potency of (E)-4-(ethoxymethylene)-2-phenyloxazol-5(4H)-one.

(E)-4-(ethoxymethylene)-2-phenyloxazol-5(4H)-one, commonly referred to as oxazolone, is the most potent skin sensitizer in published databases as determined with the murine local lymph node assay. It has been used very widely in immunological research to induce and elicit skin sensitization reactions in experimental animals. Nevertheless, no detailed study on the reactivity of oxazolone with proteins or peptides has been published, which would rationalize its unique sensitization potential from a chemical point of view. Peptide reactivity assays have been proposed as alternatives to animal tests to study the skin sensitization potential of test chemicals. Besides their application to reduce animal experimentation, peptide reactivity assays also allow one to gain mechanistic insights into the reactivity of test chemicals with proteins. In this case study, we applied different peptide reactivity assays to investigate and mechanistically rationalize the reactivity of oxazolone. Its sensitization potential could be linked to the following findings: (i) oxazolone reacts rapidly with the amine group in lysine with an addition-elimination reaction at the ethoxymethylene group to form stable products within minutes at physiological pH; (ii) sequentially different products with cysteine-peptides are formed, the most stable being an S-hippuryl-modification; and (iii) the S-hippuryl-modification can be shuttled to other nucleophilic sites; thus, also Lys residues can subsequently be modified with a hippuryl-moiety. This very rapid and diverse reactivity especially with lysine residues may explain why oxazolone forms sufficient stable novel epitopes on proteins to induce skin sensitization even at very low concentration.

Lack of evidence for HLA-linked patterns of odorous carboxylic acids released from glutamine conjugates secreted in the human axilla.

Genetic factors within the major histocompatibility locus (MHC) have been shown to influence body odors in mice. MHC-dependent preferences for body odors also have been reported in humans. The axillary glands are a key odor-forming organ in humans, and it is assumed that they provide behaviorally relevant odors. Volatile carboxylic acids are the most diverse class of known axillary odorants, and the pattern of these acids is genetically determined. These acids are released by an N(alpha)-acyl-glutamine-aminoacylase present in skin bacteria. We tested a hypothesis concerning whether or not the inherited individual-specific patterns of odorous acids are strongly influenced by polymorphic genes in the MHC. Axilla secretions were collected in 12 families, comprising 3 to 6 siblings, who had been typed for HLA-A, B, and DRB1 loci. The samples were treated with N(alpha)-acyl-glutamine-aminoacylase, and the methyl esters of the released acids were analyzed with comprehensive two-dimensional gas chromatography (GC x GC) and time-of-flight mass spectrometry (ToF MS). The patterns of the analytes were compared by distance analysis. The distance was lowest between samples taken from the same individual, confirming the presence of donor-specific odor-prints. A much higher distance was observed between siblings, but there were no differences among siblings sharing none, one, or both HLA-A,B,DRB1 haplotypes. By applying principal component analysis, a clear clustering of samples taken from one individual was confirmed, but no clustering was observed for siblings sharing identical HLA-A,B,DRB1 alleles. Thus, the genetically determined pattern of N-acyl-glutamine conjugates of volatile carboxylic acids, secreted in the human axilla, appears not to be determined by genes residing in the HLA complex.

A functional ABCC11 allele is essential in the biochemical formation of human axillary odor.

The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G --> A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G --> A, which also determines human earwax type, is present on an extended haplotype, which has reached >95% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele.

Body odour of monozygotic human twins: a common pattern of odorant carboxylic acids released by a bacterial aminoacylase from axilla secretions contributing to an inherited body odour type.

It is currently not fully established whether human individuals have a genetically determined, individual-specific body odour. Volatile carboxylic acids are a key class of known human body odorants. They are released from glutamine conjugates secreted in axillary skin by a specific Nalpha-acyl-glutamine-aminoacylase present in skin bacteria. Here, we report a quantitative investigation of these odorant acids in 12 pairs of monozygotic twins. Axilla secretions were sampled twice and treated with the Nalpha-acyl-glutamine-aminoacylase. The released acids were analysed as their methyl esters with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry detection. The pattern of the analytes was compared with distance analysis. The distance was lowest between samples of the right and the left axilla taken on the same day from the same individual. It was clearly greater if the same subject was sampled on different days, but this intra-individual distance between samples was only slightly lower than the distance between samples taken from two monozygotic twins. A much greater distance was observed when comparing unrelated individuals. By applying cluster and principal component analyses, a clear clustering of samples taken from one pair of monozygotic twins was also confirmed. In conclusion, the specific pattern of precursors for volatile carboxylic acids is subject to a day-to-day variation, but there is a strong genetic contribution. Therefore, humans have a genetically determined body odour type that is at least partly composed of these odorant acids.

Performance and reliability of splitless microliter gradient pumps in a metabolic stability study using cytochrome P450/3A4 and capillary liquid chromatography-mass spectrometry.

The performance of two commercially available capillary LC pumps (MicroPro (Eldex, USA), Evolution 200 (ProLab, Switzerland)) generating really splitless gradients in the microliter per minute range was tested in detail concerning their applicability for routine drug discovery. A standard method to study metabolic stability against CYP450 isoform 3A4 was selected. This method was transformed into a fast splitless capillary LC-MS method. Both pumps generated reproducible gradients at flows of 5-10 microl/min within 10-15 min. Although gradient formation of the MicroPro system was very reproducible, its equilibration time was too long for fast gradients around 5 microl/min. The Evolution 200 pump offered a good performance with 180 microm i.d. columns at a flow rate of 6 microl/min. The precision of the retention time of the internal standard (ISTD) varied between 1.4 and 3.4% (n = 131-152, three different columns tested). Up to 800 injections of sufficient performance on one column and a stable enough response of the ISTD for 16 h sequence duration were obtained. Accuracy between 95 and 105% and precision < or = 8.4% for 1'-hydroxylated midozolam were reached. The IC50 values of the miniaturized assay (drug candidate BAL4815 1.7 +/- 0.5, itraconazole 0.46 +/- 0.06, and ketoconazole 0.12 +/- 0.01 microM) agreed well with those of the conventional approach. Details concerning method optimization and limitations in operation are discussed in detail. Still, the overall performance of the capillary LC pumps cannot cope completely with that of conventional HPLC pumps in terms of user-friendliness.

Differentiation of isomeric flavone/isoflavone aglycones by MS2 ion trap mass spectrometry and a double neutral loss of CO.

The fragmentation behaviour of seven pairs of isomeric flavone/isoflavone aglycones (solely hydroxylated and/or methoxylated) was studied using ion trap mass spectrometry with atmospheric pressure ionisation (API, both electrospray and APCI) in the positive and negative ion modes. A major difference was found in the neutral loss of 56 u, which was a common feature of all isoflavones in API(+). It was identified as a double loss of CO by accurate mass tandem mass spectrometric (MS/MS) measurements using a hybrid quadrupole time-of-flight (Q-TOF) instrument. Fragmentation of daidzein with (13)C-isotope labelling of the carbon C2 showed that this double loss occurred from the central ring of the molecule. A mechanism for this selective fragmentation is given. Further isoflavone-specific fragmentations were used to develop a guideline for the identification of isoflavone structures. A software-based neutral loss scan of 56 u in the API(+)-MS(2) mode was applied to extracts of leaves of Lupinus albus and to soy flour. The structure elucidation guideline allowed identification of hydroxy and/or methoxy isoflavones. Structures could be confirmed for those available as reference compounds.