Effects of caloric and nutrient content of oral fluids on gastric emptying in volunteers: a randomised crossover study.

BACKGROUND: Previous studies demonstrated conflicting results regarding the determinants of gastric emptying for fluids. Our aim was to compare gastric emptying times of fluids with different caloric and nutrient content. METHODS: Healthy adult volunteers underwent gastric ultrasound assessment for 4 h after consuming beverages with different caloric and nutrient content using a crossover design (oat drink with 3% fat [310 kcal], mango juice [310 kcal], oat drink with 0.5% fat [185 kcal], and blackcurrant juice [175 kcal]). Gastric emptying time, gastric content volume, and the area under the curve (AUC) of gastric content volume-time profiles were calculated. RESULTS: Eight females and eight males completed the study protocol. The mean (sd) gastric emptying times were 89 (32) min for blackcurrant juice, 127 (54) min for oat drink with 0.5% fat, 135 (36) min for mango juice, and 152 (40) min for oat drink with 3% fat. Gastric emptying times were slower for oat drink with 3% fat (P=0.007) and mango juice (P=0.025) than for blackcurrant juice. At 1 h after ingestion, gastric content volume was greater for mango juice (P=0.021) and oat drink with 3% fat (P=0.003) than for blackcurrant juice. The AUC was greater for oat drink with 3% fat than mango juice (P=0.029), oat drink with 0.5% fat (P=0.004), and blackcurrant juice (P=0.002), and for mango juice than blackcurrant juice (P=0.019). CONCLUSIONS: Caloric and nutrient content significantly affected gastric emptying times. A high-calorie fruit juice (mango) exhibited delayed emptying times compared with a low-calorie fruit juice (blackcurrant). CLINICAL TRIAL REGISTRATION: ISRCTN17147574.

α-Aminophosphonate inhibitors of metallo-ß-lactamases NDM-1 and VIM-2.

The upswing of antibiotic resistance is an escalating threat to human health. Resistance mediated by bacterial metallo-ß-lactamases is of particular concern as these enzymes degrade ß-lactams, our most frequently prescribed class of antibiotics. Inhibition of metallo-ß-lactamases could allow the continued use of existing ß-lactam antibiotics, such as penicillins, cephalosporins and carbapenems, whose applicability is becoming ever more limited. The design, synthesis, and NDM-1, VIM-2, and GIM-1 inhibitory activities (IC50 4.1-506 µM) of a series of novel non-cytotoxic α-aminophosphonate-based inhibitor candidates are presented herein. We disclose the solution NMR spectroscopic and computational investigation of their NDM-1 and VIM-2 binding sites and binding modes. Whereas the binding modes of the inhibitors are similar, VIM-2 showed a somewhat higher conformational flexibility, and complexed a larger number of inhibitor candidates in more varying binding modes than NDM-1. Phosphonate-type inhibitors may be potential candidates for development into therapeutics to combat metallo-ß-lactamase resistant bacteria.

Metallo-ß-Lactamase Inhibitor Phosphonamidate Monoesters.

Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain-contrary to earlier predictions-a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing ß-lactam antibiotics. Inhibition of metallo-ß-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-ß-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-ß-lactamase-resistant bacteria.

Clostridioides difficile infection in a rural New Zealand secondary care centre: an incidence case-control study.

BACKGROUND: Clostridioides difficile infection (CDI) is a form of antibiotic-associated infectious diarrhoea resulting in significant morbidity and mortality. Community-acquired disease in low-risk individuals is increasingly recognised. There are limited New Zealand data published. AIM: To determine the incidence and location of onset of CDI cases in the Manawatu region, and further describe the demographics, risk factors and prevalent C. difficile ribotypes of the population. METHODS: We performed an incidence case-control study of CDI in the Manawatu region between September 2018 and September 2019. Cases were matched to controls with a negative test for C. difficile. Demographic and comorbidity data, location of onset, drug exposure, disease recurrence and 30-day mortality were collected. Ribotype analysis was performed on C. difficile isolates. RESULTS: Thirty-two specimens tested toxin positive over 12 months, yielding an incidence of 18.3 cases per 100 000 person-years. Twenty-five percent of cases had community onset disease. Cases were more likely to have had amoxicillin/clavulanate or ceftriaxone prescribed. Elevated blood white cell count and lower HbA1c were significantly associated with CDI. The dominant ribotype was 014/020. Two cases were RT 023. CONCLUSION: Our data are similar to previous national data. RT 023 has not been previously reported in New Zealand and has been associated with severe colitis. We demonstrated a significant proportion of community-acquired cases and the true incidence might be higher. Vigilance for community onset disease is required. These data may allow observation of temporal changes in incidence and infection patterns of CDI in New Zealand.

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.

A national audit of performance standards for blood cultures in Aotearoa New Zealand: opportunities for improvement.

AIMS: To audit key quality indicators for blood culture (BC) practices across Aotearoa New Zealand to facilitate national BC practice peer review and promote BC quality improvement interventions. METHOD: Microbiology laboratories providing diagnostic services to district health board (DHB) hospitals were invited to participate. Practice was compared against published BC recommendations. Laboratories were required to submit data for BC positivity and contamination rates, BC bottle fill volume and the proportion of BC received as a single set. RESULTS: Laboratories serving 15 of the 20 DHBs participated in the audit. Nine DHBs (60%) demonstrated a positivity rate within the target range of 8% to 15%. Eight DHBs (53%) reported a contamination rate lower than the accepted 3%, but seven (47%) DHBs exceeded this target and two reported a contamination rate greater than 5%. Mean BC bottle fill volumes were generally greater than the target of 8mL, but this volume was not reached by three DHBs and a further three were unable to provide fill volume data. No DHB met the audit standard for single-set BCs representing <20%, and for six DHBs single-set BC comprised more than half of all samples. No DHB failed all audit targets. CONCLUSION: This audit demonstrates wide variation in BC performance across New Zealand. In most instances an inadequate volume of blood is being collected, lowering the chance of culturing a pathogen. A significant opportunity for improvement exists; clinical services and laboratories are encouraged to work together to implement targeted quality improvement processes to correct deficiencies in practice.

What Influences People's Tradeoff Decisions Between CO2 Emissions and Travel Time? An Experiment With Anchors and Normative Messages.

One of the today's greatest challenges is to adjust our behavior so that we can avoid a major climate disaster. To do so, we must make sacrifices for the sake of the environment. The study reported here investigates how anchors (extrinsic motivational-free information) and normative messages (extrinsic motivational information) influence people's tradeoffs between travel time and carbon dioxide (CO2) emissions in the context of car travel and whether any interactions with environmental concern (an intrinsic motivational factor) can be observed. In this study, people received either a CO2, health or no normative message together with either a high anchor, a low anchor, or no anchor. People that received both a high anchor and a CO2 emission normative message were willing to travel for a longer time than those that only received a high anchor. If a low anchor was presented, no differences in willingness to travel for a longer time were found between the three different conditions of normative message groups, i.e., CO2 normative message, health normative message, or no normative message. People with higher concern for the environment were found to be willing to travel for a longer time than those with lower concern for the environment. Further, this effect was strongest when a high anchor was presented. These results suggest that anchors and normative messages are among the many factors that can influence people's tradeoffs between CO2 emission and travel time, and that various factors may have to be combined to increase their influence over pro-environmental behavior and decisions.

Early prediction of blood stream infection in a prospectively collected cohort.

BACKGROUND: Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score. METHODS: Adult patients (≥ 18 years) presenting at the emergency department (ED) with suspected BSI were prospectively included between 2014 and 2016 at Örebro University Hospital. Besides extra blood sampling, all study patients were treated according to ED routines. Electronic patient charts were retrospectively reviewed. A modified Shapiro score (MSS) and NLCR were extracted and compiled. Continuous score variables were analysed with area under receiver operator characteristics curves (AUC) to evaluate the ability of BSI prediction. RESULTS: The final cohort consisted of 484 patients where 84 (17%) had positive blood culture judged clinically significant. At optimal cut-offs, MSS (≥3 points) and NLCR (> 12) showed equal ability to predict BSI in the whole cohort (AUC 0.71/0.74; sensitivity 69%/67%; specificity 64%/68% respectively) and in a subgroup of 155 patients fulfilling Sepsis-3 criteria (AUC 0.71/0.66; sensitivity 81%/65%; specificity 46%/57% respectively). In BSI cases only predicted by NLCR> 12 the abundance of Gram-negative to Gram-positive pathogens (n = 13 to n = 4) differed significantly from those only predicted by MSS ≥3 p (n = 7 to n = 12 respectively) (p < 0.05). CONCLUSIONS: MSS and NLCR predicted BSI in the RISE cohort with similar cut-offs as shown in previous studies. Combining the MSS and NLCR did not increase the predictive performance. Differences in BSI prediction between MSS and NLCR regarding etiology need further evaluation.

Biased Estimates of Environmental Impact in the Negative Footprint Illusion: The Nature of Individual Variation.

People consistently act in ways that harm the environment, even when believing their actions are environmentally friendly. A case in point is a biased judgment termed the negative footprint illusion, which arises when people believe that the addition of "eco-friendly" items (e.g., environmentally certified houses) to conventional items (e.g., standard houses), reduces the total carbon footprint of the whole item-set, whereas the carbon footprint is, in fact, increased because eco-friendly items still contribute to the overall carbon footprint. Previous research suggests this illusion is the manifestation of an "averaging-bias." We present two studies that explore whether people's susceptibility to the negative footprint illusion is associated with individual differences in: (i) environment-specific reasoning dispositions measured in terms of compensatory green beliefs and environmental concerns; or (ii) general analytic reasoning dispositions measured in terms of actively open-minded thinking, avoidance of impulsivity and reflective reasoning (indexed using the Cognitive Reflection Test; CRT). A negative footprint illusion was demonstrated when participants rated the carbon footprint of conventional buildings combined with eco-friendly buildings (Study 1 and 2) and conventional cars combined with eco-friendly cars (Study 2). However, the illusion was not identified in participants' ratings of the carbon footprint of apples (Study 1 and 2). In Studies 1 and 2, environment-specific dispositions were found to be unrelated to the negative footprint illusion. Regarding reflective thinking dispositions, reduced susceptibility to the negative footprint illusion was only associated with actively open-minded thinking measured on a 7-item scale (Study 1) and 17-item scale (Study 2). Our findings provide partial support for the existence of a negative footprint illusion and reveal a role of individual variation in reflective reasoning dispositions in accounting for a limited element of differential susceptibility to this illusion.

Binding of 2-(Triazolylthio)acetamides to Metallo-ß-lactamase CcrA Determined with NMR.

Metallo-ß-lactamase (MBL)-producing bacteria resistant to ß-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4-6). Inhibitor 6 showed the best binding affinity (K d ≈ 2.3 ± 0.3 µM), followed by 4 (K d = 11 ± 11 µM) and 5 (K d = 34 ± 43 µM), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1-3) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.

Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study.

BACKGROUND: A light breakfast has been found to empty from the stomach within 4 hours in healthy volunteers. AIM: The aim of this study was to investigate whether a light breakfast of yoghurt or gruel empties from the stomach within 4 hours, in children scheduled for general anaesthesia. METHOD: In this observational cohort study, children aged 1-6 years scheduled for elective general anaesthesia were prescribed free intake of yoghurt or gruel 4 hours prior to induction. They were subsequently examined with gastric ultrasound within 4 hours of ingestion. In case of gastric contents, the gastric antral area was measured, and gastric content volume (GCV) was calculated. RESULTS: Twenty children were included in the study and the ingested amount of gruel or yoghurt ranged 2.5-25 mL kg-1 . In 15 cases, the stomach was empty with juxtaposed walls and no further measurements were made. In four cases, there was fluid present in the stomach, but the calculated gastric contents were <0.5 mL kg-1 . One patient had solids in the stomach, and GCV in this patient was calculated to 2.1 mL kg-1 . The patient with solids present had ingested 25 mL kg-1 of gruel 4 hours prior to assessment. The planned procedure was therefore delayed 1 hour. There were no cases of pulmonary aspiration or vomiting. CONCLUSION: A light breakfast 4 hours prior to induction may be considered, but there is need for further studies on safe limits for the volume ingested.

Kortare preoperativ fasta för barn bör övervägas - Europeisk rekommendation om en timmes fasta för klar dryck.

International guidelines for paediatric elective preoperative fasting currently recommend a 2 hour limit for clear fluids. Recent reports on gastric emptying time, pulmonary aspiration incidence and the negative effects of fasting have led to a new consensus statement by the European Society of Paediatric Anaesthesia, recommending a 1-hour limit for clear fluids. A multicentre audit of the incidence of aspiration with the new fasting regimens is still needed.

Carbon's Three-Center, Four-Electron Tetrel Bond, Treated Experimentally.

Tetrel bonding is the noncovalent interaction of group IV elements with electron donors. It is a weak, directional interaction that resembles hydrogen and halogen bonding yet remains barely explored. Herein, we present an experimental investigation of the carbon-centered, three-center, four-electron tetrel bond, [N-C-N]+, formed by capturing a carbenium ion with a bidentate Lewis base. NMR-spectroscopic, titration-calorimetric, and reaction-kinetic evidence for the existence and structure of this species is reported. The studied interaction is by far the strongest tetrel bond reported so far and is discussed in comparison with the analogous halogen bond. The necessity of the involvement of a bidentate Lewis base in its formation is demonstrated by providing spectroscopic and crystallographic evidence that a monodentate Lewis base induces a reaction rather than stabilizing the tetrel bond complex. A vastly decreased Lewis basicity of the bidentate ligand or reduced Lewis acidity of the carbenium ion weakens-or even prohibits-the formation of the tetrel bond complex, whereas synthetic modifications facilitating attractive orbital overlaps promote it. As the geometry of the complex resembles the SN2 transition state, it provides a model system for the investigation of fundamental reaction mechanisms and chemical bonding theories.

Preoperative fasting guidelines in pediatric anesthesia: are we ready for a change?

PURPOSE OF REVIEW: Study after study shows that prolonged fasting before anesthesia is common in children. Pediatric anesthesiologists around the world are concerned that the current guidelines may be part of the problem. This review focuses on what can be done about it. RECENT FINDINGS: We discuss new insights into the physiology of gastric emptying of different categories of food and drink. The evidence for negative effects of prolonged fasting occurring in spite of implementation of the current guidelines is examined. We also critically appraise the concept of a strict association between fasting time and the risk of aspiration and discuss recent studies in which children have been allowed clear fluids less than 2 h before anesthesia induction. SUMMARY: Accumulating evidence indicates that changes of the current guidelines for preoperative fasting should be considered for children undergoing elective procedures. VIDEO ABSTRACT.

Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children.

BACKGROUND: Children often starve for longer than recommended by current preoperative fasting guidelines. AIMS: We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children. METHODS: Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1 year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison. RESULTS: Patients fasting according to the 6-4-2 fasting regimen (n = 66) had a median fasting time for clear fluids of 4.0 h and a 33.3% incidence of fasting more than 6 h. After transitioning to the 6-4-0 fasting regimen (n = 64), median duration of fasting for clear fluids decreased to 1.0 h, and the incidence of fasting more than 6 h decreased to 6.3%. In the second unit (n = 73), median fasting time was 2.2 h and the proportion of patients fasting more than 6 h was 21.9%. CONCLUSION: The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

Comorbidity of Airway Inflammatory Diseases in Chemical and Building-Related Intolerance.

OBJECTIVES: This study investigated comorbidity in chemical intolerance (CI) and building- related intolerance (BRI) with (i) chronic sinusitis, chronic obstructive pulmonary disease, allergic and nonallergic asthma and allergic rhinitis, and (ii) airway inflammatory symptoms. METHODS: Data from two population-based questionnaire surveys, the Västerbotten and Österbotten Environmental Health Studies, were used. The participants were categorized as CI or BRI and referents, and binary logistic regression analysis was applied. RESULTS: Prevalence rates for the case groups were 7.2% to 40.0% for diseases and 24.3% to 68.9% for symptoms, whereas adjusted odds ratios (ORs) were 3.4 to 26.1 for diseases and 3.3 to 17.0 for symptoms, all being significantly higher than unity. Prevalence rates and ORs were in general higher in BRI than in CI. CONCLUSION: Inflammatory airway diseases and symptoms are associated with CI and BRI, which encourages further research regarding underlying mechanisms and treatments.

Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation.

Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a ß-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.

Assessing the Ability of Spectroscopic Methods to Determine the Difference in the Folding Propensities of Highly Similar ß-Hairpins.

We have evaluated the ability of nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopies to describe the difference in the folding propensities of two structurally highly similar cyclic ß-hairpins, comparing the outcome to that of molecular dynamics simulations. NAMFIS-type NMR ensemble analysis and CD spectroscopy were observed to accurately describe the consequence of altering a single interaction site, whereas a single-site 13C NMR chemical shift melting curve-based technique was not.

Photochemically Induced Aryl Azide Rearrangement: Solution NMR Spectroscopic Identification of the Rearrangement Product.

Photolysis of ethyl 3-azido-4,6-difluorobenzoate at room temperature in the presence of oxygen results in the regioselective formation of ethyl 5,7-difluoro-4-azaspiro[2.4]hepta-1,4,6-triene-1-carboxylate, presumably via the corresponding ketenimine intermediate which undergoes a photochemical four-electron electrocyclization followed by a rearrangement. The photorearrangement product was identified by multinuclear solution NMR spectroscopic techniques supported by DFT calculations.