A CuI6L4 Cage Dynamically Reconfigures to Form Suit[4]anes and Selectively Bind Fluorinated Steroids.

Simple organic ligands can self-assemble with metal ions to generate metal-organic cages, whose cavities bind guests selectively. This binding may enable new methods of chemical separation or sensing, among other useful functions. Here we report the preparation of a CuI6L4 pseudo-octahedral metal-organic cage, the ligands of which self-assemble from simple organic building blocks. Temperature, solvent, and the presence of different guests governed which structure predominated from a dynamic mixture of cage diastereomers with different arrangements of right- or left-handed metal vertices. Dissolution in dimethyl sulfoxide or the binding of tetrahedral guests led to a chiral tetrahedral T-symmetric framework, whereas low temperatures favored the achiral S4-symmetric diastereomer. Tetrahedral guests with long arms were encapsulated to form mechanically bonded suit[4]anes, with guest arms protruding out through host windows. The cage was also observed to bind fluorinated steroids, an important class of drug molecules, but not non-fluorinated steroids, providing the basis for new separation processes.

Metal Ions Trigger the Gelation of Cysteine-Containing Peptide-Appended Coordination Cages.

We report a series of coordination cages that incorporate peptide chains at their vertices, prepared through subcomponent self-assembly. Three distinct heterochiral tripeptide subcomponents were incorporated, each exhibiting an L-D-L stereoconfiguration. Through this approach, we prepared and characterized three tetrahedral metal-peptide cages that incorporate thiol and methylthio groups. The gelation of these cages was probed through the binding of additional metal ions, with the metal-peptide cages acting as junctions, owing to the presence of sulfur atoms on the peripheral peptides. Gels were obtained with cages bearing cysteine at the C-terminus. Our strategy for developing functional metal-coordinated supramolecular gels with a modular design may result in the development of materials useful for chemical separations or drug delivery.

A Diverse Array of Large Capsules Transform in Response to Stimuli.

The allosteric regulation of biomolecules, such as enzymes, enables them to adapt and alter their conformation to fit specific substrates, expressing different functionalities in response to stimuli. Different stimuli can also trigger synthetic coordination cages to change their shape, size, and nuclearity by reconfiguring the dynamic metal-ligand bonds that hold them together. Here we demonstrate an abiological system consisting of different organic subcomponents and ZnII metal ions, which can respond to simple stimuli in complex ways. A ZnII20L12 dodecahedron transforms to give a larger ZnII30L12 icosidodecahedron through subcomponent exchange, as an aldehyde that forms bidentate ligands is displaced in favor of one that forms tridentate ligands together with a penta-amine subcomponent. In the presence of a chiral template guest, the same system that produced the icosidodecahedron instead gives a ZnII15L6 truncated rhombohedral architecture through enantioselective self-assembly. Under specific crystallization conditions, a guest induces a further reconfiguration of either the ZnII30L12 or ZnII15L6 cages to yield an unprecedented ZnII20L8 pseudo-truncated octahedral structure. The transformation network of these cages shows how large synthetic hosts can undergo structural adaptation through the application of chemical stimuli, opening pathways to broader applications.

A Double-Walled Tetrahedron with AgI 4 Vertices Binds Different Guests in Distinct Sites.

A double-walled tetrahedral metal-organic cage assembled in solution from silver(I), 2-formyl-1,8-naphthyridine, halide, and a threefold-symmetric triamine. The AgI 4 X clusters at its vertices each bring together six naphthyridine-imine moieties, leading to a structure in which eight tritopic ligands bridge four clusters in an (AgI 4 X)4 L8 arrangement. Four ligands form an inner set of tetrahedron walls that are surrounded by the outer four. The cage has significant interior volume, and was observed to bind anionic guests. The structure also possesses external binding clefts, located at the edges of the cage, which bound small aromatic guests. Halide ions bound to the silver clusters were observed to exchange in a well-defined hierarchy, allowing modulation of the cavity volume. The principles uncovered here may allow for increasingly more sophisticated cages with silver-cluster vertex architectures, with post-assembly tuning of the interior cavity volume enabling targeted binding behavior.

A Hydrogen-Bonded Ravel Assembled by Anion Coordination.

Anion-coordination-driven assembly (ACDA) is showing increasing power in the construction of anionic supramolecular architectures. Herein, by expanding the anion centers from oxoanion (phosphate or sulfate) to organic tris-carboxylates, an Archimedean solid (truncated tetrahedron) and a highly entangled, double-walled tetrahedron featuring a ravel topology have been assembled with tris-bis(urea) ligands. The results demonstrate the promising ability of tris-carboxylates as new anion coordination centers in constructing novel topologies with increasing complexity and diversity compared to phosphate or sulfate ions on account of the modifiable size and easy functionalization character of these organic anions.

"Cannot intubate, cannot oxygenate": A novel 2-operator technique for cannula tracheotomy in an infant animal model-a feasibility study.

BACKGROUND: Evidence regarding optimal management of the "Cannot Intubate, Cannot Oxygenate" (CICO) scenario in infants is scarce. When inserting a transtracheal cannula for front of neck access direct aspiration to confirm intratracheal location is standard practice. This postmortem "infant airway" animal model study describes a novel technique for cannula tracheotomy. AIMS: To compare a novel technique of cannula tracheotomy to an accepted technique to assess success and complication rates. METHODS: Two experienced proceduralists repeatedly performed tracheotomy using an 18-gauge BD InsyteTM cannula (BD, Franklin Lakes, NJ, USA) in 6 postmortem White New Zealand rabbits. Cannulas were attached either directly to a 5ml syringe (Direct Aspiration) or via a 25 cm length minimum volume extension tubing set (TUTA Healthcare Lidcombe, NSW, Australia) (Indirect Aspiration, 2 operator technique). Each technique was attempted a maximum of 12 times per rabbit with an ENT surgeon assessing success and complication rates endoscopically for each attempt. RESULTS: 72 tracheotomy attempts were made in total, 36 for each technique. Initial aspiration through the needle was achieved in 93% (97.2% direct versus 89% indirect). Advancement of the cannula and continued aspiration (success) into the trachea occurred in 67% for direct compared with 64% for indirect aspiration. Direct aspiration was associated with higher rates of lateral (10.3% versus 5.6%) and posterior (19.4% versus 13.9%) wall injury compared with the indirect 2-operator technique. CONCLUSION: Cannula tracheotomy in infant-sized airways is technically difficult and seems frequently associated with tracheal wall injury. The reduced incidence of injury in the indirect group warrants further investigation in preclinical and clinical trials.

Front-of-neck airway rescue with impalpable anatomy during a simulated cannot intubate, cannot oxygenate scenario: scalpel-finger-cannula versus scalpel-finger-bougie in a sheep model.

BACKGROUND: Front-of-neck airway rescue in a cannot intubate, cannot oxygenate (CICO) scenario with impalpable anatomy is particularly challenging. Several techniques have been described based on a midline vertical neck incision with subsequent finger dissection, followed by either a cannula or scalpel puncture of the now palpated airway. We explored whether the speed of rescue oxygenation differs between these techniques. METHODS: In a high-fidelity simulation of a CICO scenario in anaesthetised Merino sheep with impalpable front-of-neck anatomy, 35 consecutive eligible participants undergoing airway training performed scalpel-finger-cannula and scalpel-finger-bougie in a random order. The primary outcome was time from airway palpation to first oxygen delivery. Data, were analysed with Cox proportional hazards. RESULTS: Scalpel-finger-cannula was associated with shorter time to first oxygen delivery on univariate (hazard ratio [HR]=11.37; 95% confidence interval [CI], 5.14-25.13; P<0.001) and multivariate (HR=8.87; 95% CI, 4.31-18.18; P<0.001) analyses. In the multivariable model, consultant grade was also associated with quicker first oxygen delivery compared with registrar grade (HR=3.28; 95% CI, 1.36-7.95; P=0.008). With scalpel-finger-cannula, successful oxygen delivery within 3 min of CICO declaration and ≤2 attempts was more frequent; 97% vs 63%, P<0.001. In analyses of successful cases only, scalpel-finger-cannula resulted in earlier improvement in arterial oxygen saturations (-25 s; 95% CI, -35 to -15; P<0.001), but a longer time to first capnography reading (+89 s; 95% CI, 69 to 110; P<0.001). No major complications occurred in either arm. CONCLUSIONS: The scalpel-finger-cannula technique was associated with superior oxygen delivery performance during a simulated CICO scenario in sheep with impalpable front-of-neck anatomy.

Effect of Apneic Oxygenation on Tracheal Oxygen Levels, Tracheal Pressure, and Carbon Dioxide Accumulation: A Randomized, Controlled Trial of Buccal Oxygen Administration.

BACKGROUND: Apneic oxygenation via the oral route using a buccal device extends the safe apnea time in most but not all obese patients. Apneic oxygenation techniques are most effective when tracheal oxygen concentrations are maintained >90%. It remains unclear whether buccal oxygen administration consistently achieves this goal and whether significant risks of hypercarbia or barotrauma exist. METHODS: We conducted a randomized trial of buccal or sham oxygenation in healthy, nonobese patients (n = 20), using prolonged laryngoscopy to maintain apnea with a patent airway until arterial oxygen saturation (SpO2) dropped <95% or 750 seconds elapsed. Tracheal oxygen concentration, tracheal pressure, and transcutaneous carbon dioxide (CO2) were measured throughout. The primary outcome was maintenance of a tracheal oxygen concentration >90% during apnea. RESULTS: Buccal patients were more likely to achieve the primary outcome (P < .0001), had higher tracheal oxygen concentrations throughout apnea (mean difference, 65.9%; 95% confidence interval [CI], 62.6%-69.3%; P < .0001), and had a prolonged median (interquartile range) apnea time with SpO2 >94%; 750 seconds (750-750 seconds) vs 447 seconds (405-525 seconds); P < .001. One patient desaturated to SpO2 <95% despite 100% tracheal oxygen. Mean tracheal pressures were low in the buccal (0.21 cm·H2O; SD = 0.39) and sham (0.56 cm·H2O; SD = 1.25) arms; mean difference, -0.35 cm·H2O; 95% CI, 1.22-0.53; P = .41. CO2 accumulation during early apnea before any study end points were reached was linear and marginally faster in the buccal arm (3.16 vs 2.82 mm Hg/min; mean difference, 0.34; 95% CI, 0.30-0.38; P < .001). Prolonged apnea in the buccal arm revealed nonlinear CO2 accumulation that declined over time and averaged 2.22 mm Hg/min (95% CI, 2.21-2.23). CONCLUSIONS: Buccal oxygen administration reliably maintains high tracheal oxygen concentrations, but early arterial desaturation can still occur through mechanisms other than device failure. Whereas the risk of hypercarbia is similar to that observed with other approaches, the risk of barotrauma is negligible. Continuous measurement of advanced physiological parameters is feasible in an apneic oxygenation trial and can assist with device evaluation.

SciPhon: a data analysis software for nuclear resonant inelastic X-ray scattering with applications to Fe, Kr, Sn, Eu and Dy.

The synchrotron radiation technique of nuclear resonant inelastic X-ray scattering (NRIXS), also known as nuclear resonance vibrational spectroscopy or nuclear inelastic scattering, provides a wealth of information on the vibrational properties of solids. It has found applications in studies of lattice dynamics and elasticity, superconductivity, heme biochemistry, seismology, isotope geochemistry and many other fields. It involves probing the vibrational modes of solids by using the nuclear resonance of Mössbauer isotopes such as 57Fe, 83Kr, 119Sn, 151Eu and 161Dy. After data reduction, it provides the partial phonon density of states of the Mössbauer isotope that is investigated, as well as many other derived quantities such as the mean force constant of the chemical bonds and the Debye velocity. The data reduction is, however, not straightforward and involves removal of the elastic peak, normalization and Fourier-Log transformation. Furthermore, some of the quantities derived are highly sensitive to details in the baseline correction. A software package and several novel procedures to streamline and hopefully improve the reduction of the NRIXS data generated at sector 3ID of the Advanced Photon Source have been developed. The graphical user interface software is named SciPhon and runs as a Mathematica package. It is easily portable to other platforms and can be easily adapted for reducing data generated at other beamlines. Several tests and comparisons are presented that demonstrate the usefulness of this software, whose results have already been used in several publications. Here, the SciPhon software is used to reduce Kr, Sn, Eu and Dy NRIXS data, and potential implications for interpreting natural isotopic variations in those systems are discussed.

A cross-sectional investigation into the occupational and socio-demographic characteristics of British police force employees reporting a dietary pattern associated with cardiometabolic risk: findings from the Airwave Health Monitoring Study.

PURPOSE: The aims of this study were to (1) determine the association between diet quality using the Dietary Approaches to Stop Hypertension (DASH) score and cardiometabolic risk in a British working population and (2) identify employee characteristics associated with reporting a poorer quality dietary pattern. METHODS: British police employees enrolled (2007-2012) into the Airwave Health Monitoring Study (n = 5527) were included for sex-specific cross-sectional analyses. Dietary intakes were measured using 7-day food records. DASH score was calculated to determine diet quality. Logistic regression evaluated associations between (1) diet quality and increased cardiometabolic risk (defined as ≥ 3 risk markers: dyslipidaemia, elevated blood pressure, waist circumference, CRP or HbA1c), and (2) poor diet quality (lowest fifth of DASH score distribution) and employee characteristics. RESULTS: Employees recording a poor diet quality had greater odds (OR) of increased cardiometabolic risk independent of established risk factors (demographic, lifestyle and occupational) and BMI: men OR 1.50 (95% CI 1.12-2.00), women: OR 1.84 (95% CI 1.19-2.97) compared to the healthiest diet group. Characteristics associated with reporting a poor quality diet were employment in Scotland vs. England: men OR 1.88 (95% CI 1.53-2.32), women: OR 1.49 (95% CI 1.11-2.00), longer working hours (≥ 49 vs. ≤40 h) men: OR 1.53 (95% CI 1.21-1.92) women: OR 1.53 (95% CI 1.12-2.09). For men, job strain (high vs. low) was associated with reporting a poor diet quality OR 1.66 (95% CI 1.30-2.12). CONCLUSIONS: The general population disparities in diet quality between England and Scotland were reflected in British police employees. The association of longer working hours and job strain with diet quality supports the targeting of workplace nutritional interventions.

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: A Randomized, Controlled Trial of Buccal RAE Tube Oxygen Administration.

BACKGROUND: Despite optimal preoxygenation, obese patients undergoing induction of general anesthesia exhibit significant hypoxemia after 2 to 4 minutes of apnea. Apneic oxygenation techniques can assist airway management by extending the safe apnea time. We hypothesized that a novel method of apneic oxygenation via the oral route would effectively prolong safe apnea in an obese surgical population. METHODS: In this open-label, parallel-arm, randomized-controlled efficacy trial, 40 ASA physical status I-II obese patients with body mass index (BMI) 30-40 were randomly assigned to standard care (n = 20) or buccal oxygenation (n = 20) during induction of total IV anesthesia. Buccal oxygen was administered via a modified 3.5-mm Ring-Adair-Elwyn (RAE) tube apposed to the left internal cheek. Prolonged laryngoscopy maintained apnea with a patent airway until SpO2 dropped below 95% or 750 seconds elapsed. The primary outcome was time to reach SpO2 < 95%. RESULTS: Patient characteristics were similar in both study arms. Recipients of buccal oxygenation were less likely to exhibit SpO2 < 95% during 750 seconds of apnea; hazard ratio 0.159 (95% confidence interval 0.044-0.226, P < .0001). Median (interquartile range [IQR]) apnea times with SpO2 ≥ 95% were prolonged in this group; 750 (389-750) versus 296 (244-314) seconds, P < .0001. CONCLUSIONS: Clinically important prolongation of safe apnea times can be achieved delivering buccal oxygen to obese patients on induction of anesthesia. This novel use of apneic oxygenation via the oral route may improve management of the difficult airway and overcome some of the limitations of alternative techniques.

Acute Exposure to Terrestrial Trunked Radio (TETRA) has effects on the electroencephalogram and electrocardiogram, consistent with vagal nerve stimulation.

BACKGROUND: Terrestrial Trunked Radio (TETRA) is a telecommunications system widely used by police and emergency services around the world. The Stewart Report on mobile telephony and health raised questions about possible health effects associated with TETRA signals. This study investigates possible effects of TETRA signals on the electroencephalogram and electrocardiogram in human volunteers. METHODS: Blinded randomized provocation study with a standardized TETRA signal or sham exposure. In the first of two experiments, police officers had a TETRA set placed first against the left temple and then the upper-left quadrant of the chest and the electroencephalogram was recorded during rest and active cognitive processing. In the second experiment, volunteers were subject to chest exposure of TETRA whilst their electroencephalogram and heart rate variability derived from the electrocardiogram were recorded. RESULTS: In the first experiment, we found that exposure to TETRA had consistent neurophysiological effects on the electroencephalogram, but only during chest exposure, in a pattern suggestive of vagal nerve stimulation. In the second experiment, we observed changes in heart rate variability during exposure to TETRA but the electroencephalogram effects were not replicated. CONCLUSIONS: Observed effects of exposure to TETRA signals on the electroencephalogram (first experiment) and electrocardiogram are consistent with vagal nerve stimulation in the chest by TETRA. However given the small effect on heart rate variability and the lack of consistency on the electroencephalogram, it seems unlikely that this will have a significant impact on health. Long-term monitoring of the health of the police force in relation to TETRA use is on-going.

A case series of the Royal Perth Hospital cannula-first approach in the 'can't intubate, can't oxygenate' scenario.

At the Royal Perth Hospital, we have been developing and teaching a can't intubate, can't oxygenate (CICO) rescue algorithm for over 19 years, based on live animal simulation. The algorithm involves a 'cannula-first' approach, with jet oxygenation and progression to scalpel techniques if required in a stepwise fashion. There is little reported experience of this approach to the CICO scenario in humans. We present eight cases in which a cannula-first Royal Perth Hospital approach was successfully implemented during an airway crisis. We recommend that institutions teach and practice this approach; we believe it is effective, safe and minimally invasive when undertaken by clinicians who have been trained in it and have immediate access to the requisite equipment. The equipment is low cost, comprising a 14G Insyte cannula, saline, 5 ml syringe and a Rapid-O2. Training can be provided using low-fidelity manikins or part-task trainers.

Enantioselective fullerene functionalization through stereochemical information transfer from a self-assembled cage.

The regioselective functionalization of C60 remains challenging, while the enantioselective functionalization of C60 is difficult to explore due to the need for complex chiral tethers or arduous chromatography. Metal-organic cages have served as masks to effect the regioselective functionalization of C60. However, it is difficult to control the stereochemistry of the resulting fullerene adducts through this method. Here we report a means of defining up to six stereocentres on C60, achieving enantioselective fullerene functionalization. This method involves the use of a metal-organic cage built from a chiral formylpyridine. Fullerenes hosted within the cavity of the cage can be converted into a series of C60 adducts through chemo-, regio- and stereo-selective Diels-Alder reactions with the edges of the cage. The chiral formylpyridine ultimately dictates the stereochemistry of these chiral fullerene adducts without being incorporated into them. Such chiral fullerene adducts may become useful in devices requiring circularly polarized light manipulation.

The 'Can't Intubate Can't Oxygenate' scenario in Pediatric Anesthesia: a comparison of different devices for needle cricothyroidotomy.

BACKGROUND: Little evidence exists to guide the management of the 'Can't Intubate, Can't Oxygenate' (CICO) scenario in pediatric anesthesia. OBJECTIVES: To compare two intravenous cannulae for ease of use, success rate and complication rate in needle tracheotomy in a postmortem animal model of the infant airway, and trial a commercially available device using the same model. METHODS: Two experienced proceduralists repeatedly attempted cannula tracheotomy in five postmortem rabbits, alternately using 18-gauge (18G) and 14-gauge (14G) BD Insyte(™) cannulae (BD, Franklin Lakes, NJ, USA). Attempts began at the first tracheal cartilage, with subsequent attempts progressively more caudad. Success was defined as intratracheal cannula placement. In each rabbit, an attempt was then made by each proceduralist to perform a cannula tracheotomy using the Quicktrach Child(™) device (VBM Medizintechnik GmbH, Sulz am Neckar, Germany). RESULTS: The rabbit tracheas were of similar dimensions to a human infant. 60 attempts were made at cannula tracheotomy, yielding a 60% success rate. There was no significant difference in success rate, ease of use, or complication rate between cannulae of different gauge. Successful aspiration was highly predictive (positive predictive value 97%) and both sensitive (89%) and specific (96%) for tracheal cannulation. The posterior tracheal wall was perforated in 42% of tracheal punctures. None of 13 attempts using the Quicktrach Child(™) were successful. CONCLUSION: Cannula tracheotomy in a model comparable to the infant airway is difficult and not without complication. Cannulae of 14- and 18-gauge appear to offer similar performance. Successful aspiration is the key predictor of appropriate cannula placement. The Quicktrach Child was not used successfully in this model. Further work is required to compare possible management strategies for the CICO scenario.

Controlling catalyst activity, chemoselectivity and stereoselectivity with the mechanical bond.

Mechanically interlocked molecules, such as rotaxanes and catenanes, are receiving increased attention as scaffolds for the development of new catalysts, driven by both their increasing accessibility and high-profile examples of the mechanical bond delivering desirable behaviours and properties. In this Review, we survey recent advances in the catalytic applications of mechanically interlocked molecules organized by the effect of the mechanical bond on key catalytic properties, namely, activity, chemoselectivity and stereoselectivity, and focus on how the mechanically bonded structure leads to the observed behaviour. Our aim is to inspire future investigations of mechanically interlocked catalysts, including those outside of the supramolecular community.

A chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes.

Rotaxanes can display molecular chirality solely due to the mechanical bond between the axle and encircling macrocycle without the presence of covalent stereogenic units. However, the synthesis of such molecules remains challenging. We have discovered a combination of reaction partners that function as a chiral interlocking auxiliary to both orientate a macrocycle and, effectively, load it onto a new axle. Here we use these substrates to demonstrate the potential of a chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes by producing a range of examples with high enantiopurity (93-99% e.e.), including so-called 'impossible' rotaxanes whose axles lack any functional groups that would allow their direct synthesis by other means. Intriguingly, by varying the order of bond-forming steps, we can effectively choose which end of an axle the macrocycle is loaded onto, enabling the synthesis of both hands of a single target using the same reactions and building blocks.

The use of ultrasound to guide time-critical cannula tracheotomy when anterior neck airway anatomy is unidentifiable.

BACKGROUND AND OBJECTIVE: Transtracheal or transcricothyroid placement of a cannula is a practice used in a number of aspects of airway management in anaesthesia and intensive care. In this study, we aimed to investigate whether the use of ultrasound will facilitate cannula placement in a time-critical situation in patients with difficult anterior neck airway anatomy. METHOD: Fifty anaesthetists were randomised to either ultrasound-guided or conventional unguided attempts, at cannula insertion into a model simulating a patient with unidentifiable anterior neck anatomy. Endpoints were the success, and time to success, of cannula placement. RESULTS: There was a significant increase in success rate (83 vs. 43%, P = 0.011) and a significant decrease in time to successful placement (median time to successful cannulation 57 vs. 110 s, P = 0.008) using ultrasound guided compared to unguided cannula placement. CONCLUSION: If a 'can't intubate, can't oxygenate' scenario occurs in a patient with unidentifiable anterior neck airway anatomy in a location where an ultrasound machine is immediately available, we recommend that consideration is given to the use of ultrasound-guided cannula tracheotomy as the first-line rescue technique.