Outcomes following surgical fixation of Gustilo-Anderson IIIb open tibial fractures.

There is no consensus as to the optimal skeletal fixation method for Gustilo-Anderson IIIb fractures. External fixation methods have previously shown higher rates of superficial infection, whilst internal fixation has shown higher risk of deep infection, but lower risk of other complications. This paper investigates outcomes in open tibial fractures based on fixation method. A retrospective review was performed for patients presenting to an ortho-plastic unit with GA IIIb tibial fractures between June 2013 and October 2021. 85 patients were identified. The most common implant was an intramedullary nail (IMN), used in 29 patients (34.1%); open reduction and internal fixation (ORIF) was performed in 16 patients (18.8%). 18 patients (21.2%) were definitively managed with a frame alone. Mean follow-up from was 18 months (2-77). Patients with ORIF needed a mean of 3.37 operations; it was 2.48 for IMN which was significantly different from frames at 5.00 (p=0.000). The mean time to bony union after definitive fixation was 11.4 months. This differed depending on the implant used for fixation, with ORIF at 7.1 months, 10.1 for IMN, and frames at 17.2 months; ORIF significantly differed from frames (p=0.009). Superficial infection was common, seen in 38.8% of patients, and only 3 patients (4%) developed deep infections involving metalwork, with no difference in rates of either based on fixation method This study supports that ORIF has faster healing times, with less time to union compared to frames. It also shows that no implant was superior to another in terms of outcomes.

Use of the Obstetric Quality-of-Recovery score (ObsQoR-11) to measure the impact of an enhanced recovery programme for elective caesarean section.

BACKGROUND: Enhanced recovery after caesarean (ERAC) has been shown to postoperatively reduce opioid consumption, reduce pain scores, and shorten hospital stay. Arguably, none of these measures provide for a patient-centred approach. We believe that patient-reported outcome measures (PROMs) represent a more holistic approach to the reporting of outcomes. One such PROM is the Obstetric Quality-of-Recovery Score (ObsQoR-11). This has been shown to be a valid and reliable assessment of recovery after elective caesarean section. METHODS: This before-and-after quality improvement programme studied consecutive patients undergoing elective caesarean section. We implemented an ERAC pathway with the aim of improving quality of recovery and patient satisfaction. Our primary outcome was the change in the ObsQoR-11 score. RESULTS: A total of 318 medical records were reviewed (n = 93 before ERAC, n = 225 after ERAC). There was a significant improvement in ObsQoR-11 score in ERAC patients compared with pre-ERAC patients (85.0 vs 82.3, P < 0.001). Morphine consumption (MMEQ) was reduced by 10% overall in the ERAC group, with no increase in pain scores at day 1 postoperatively and a decrease in pain scores on day 2 in the ERAC group (P = 0.02). The length of hospital stay was significantly shorter in ERAC patients (63.1 h vs 79.9 h, P < 0.001). CONCLUSIONS: Our study demonstrated an improved ObsQoR-11 score after ERAC implementation. This is the first example in the literature of using ObsQoR-11 in ERAC. We believe this is a more comprehensive way to assess patient recovery and the impact of an ERAC programme.

Model-based inference of a plant-specific dual role for HOPS in regulating guard cell vacuole fusion.

Stomata are the pores on a leaf surface that regulate gas exchange. Each stoma consists of two guard cells whose movements regulate pore opening and thereby control CO2 fixation and water loss. Guard cell movements depend in part on the remodeling of vacuoles, which have been observed to change from a highly fragmented state to a fused morphology during stomata opening. This change in morphology requires a membrane fusion mechanism that responds rapidly to environmental signals, allowing plants to respond to diurnal and stress cues. With guard cell vacuoles being both large and responsive to external signals, stomata represent a unique system in which to delineate mechanisms of membrane fusion. Fusion of vacuole membranes is a highly conserved process in eukaryotes, with key roles played by two multi-subunit complexes: HOPS (homotypic fusion and vacuolar protein sorting) and SNARE (soluble NSF attachment protein receptor). HOPS is a vacuole tethering factor that is thought to chaperone SNAREs from apposing vacuole membranes into a fusion-competent complex capable of rearranging membranes. To resolve a counter-intuitive observation regarding the role of HOPS in regulating plant vacuole morphology, we derived a quantitative model of vacuole fusion dynamics and used it to generate testable predictions about HOPS-SNARE interactions. We derived our model by applying simulation-based inference to integrate prior knowledge about molecular interactions with limited, qualitative observations of emergent vacuole phenotypes. By constraining the model parameters to yield the emergent outcomes observed for stoma opening - as induced by two distinct chemical treatments - we predicted a dual role for HOPS and identified a stalled form of the SNARE complex that differs from phenomena reported in yeast. We predict that HOPS has contradictory actions at different points in the fusion signaling pathway, promoting the formation of SNARE complexes, but limiting their activity.

Generalised neuromuscular blockade after intraurethral administration of atracurium besilate in a male cat with urethral obstruction.

A 4-year-old, entire, male, domestic long-haired cat was presented with an acute history of stranguria and dysuria and diagnosed with urolithiasis causing urethral obstruction. The patient was induced to general anaesthesia and several unsuccessful attempts to flush the uroliths retrogradely towards the bladder were made. An intraurethral administration of the neuromuscular blocking agent atracurium was performed as it has been reported to facilitate urethral catheterisation without any side effects. Respiratory arrest developed after 15 minutes from atracurium administration, which was promptly recognized and treated with mechanical ventilation. The absence of muscle contraction in response to a nerve stimulation confirmed a generalised muscle blockade. Approximately 35 minutes after, a muscle response to nerve stimulation appeared. Neostigmine combined with glycopyrrolate was administered resulting in complete recovery from neuromuscular blockade. In conclusion, the use of intraurethral atracurium can result in systemic absorption of the drug with subsequent generalised neuromuscular blockade.

A New Paradigm for Pandemic Preparedness.

Purpose of Review: Preparing for pandemics requires a degree of interdisciplinary work that is challenging under the current paradigm. This review summarizes the challenges faced by the field of pandemic science and proposes how to address them. Recent Findings: The structure of current siloed systems of research organizations hinders effective interdisciplinary pandemic research. Moreover, effective pandemic preparedness requires stakeholders in public policy and health to interact and integrate new findings rapidly, relying on a robust, responsive, and productive research domain. Neither of these requirements are well supported under the current system. Summary: We propose a new paradigm for pandemic preparedness wherein interdisciplinary research and close collaboration with public policy and health practitioners can improve our ability to prevent, detect, and treat pandemics through tighter integration among domains, rapid and accurate integration, and translation of science to public policy, outreach and education, and improved venues and incentives for sustainable and robust interdisciplinary work.

High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development.

New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal screens of chemical collections have played an important role in the search for new vector insecticides and the identification of active ingredients (AIs) that cause rapid mortality of mosquitoes. Advances in image-based screening offer an opportunity to identify chemistries that operate via novel biochemical modes and investigate the range of phenotypes exhibited by mosquitoes following exposure to lethal and sub-lethal chemical dose. An automated, high throughput phenotypic screen (HTS) employing high-content imaging of first instar (L1) Aedes aegypti larvae was developed to identify chemistries associated with mortality and atypical morphological phenotypes. A pilot screen of the Library of Pharmacologically Active Compounds (LOPAC1280) identified 92 chemistries that disrupted larval activity and development, including conventional insecticides and chemistries known to modulate G protein-coupled receptors (GPCRs) and other molecular targets in mammalian systems. Secondary assay series were used to evaluate a selection of chemistries for impacts on mosquito activity, survival and development. Ritodrine hydrochloride reduced mobility of larvae but had no observable effect on survival and development of mosquitoes. High doses of metergoline suppressed larval activity and sub-lethal dose resulted in pupal mortality. Assay data support the utility of phenotypic screening and diverse entomological end-points for discovery of novel insecticidal chemical scaffolds. The insecticide discovery process must consider how multi-modal efficacy spectra contribute to vector and VBD control.

Stability of dilutions of methadone alone, and in combination with lidocaine and ketamine.

OBJECTIVES: To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions. MATERIALS AND METHODS: Solutions of methadone diluted in 0.9% NaCl, and methadone-lidocaine-ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4°C and protected from light, were maintained over 10 days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240 hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time. RESULTS: There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone-lidocaine-ketamine with Hartmann's solution at 4°C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone-lidocaine-ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone-lidocaine-ketamine components retained acceptable stability (<10% degradation) for at least 48 hours following preparation, irrespective of diluent or storage conditions. CLINICAL SIGNIFICANCE: Regardless of the diluent or storage method, methadone-lidocaine-ketamine solutions degrade over time, but this only becomes clinically significant after 48 hours. Solutions of 1 mg/ml methadone in 0.9% NaCl are stable for at least 10 days under storage conditions likely to be encountered in general practice.

Infrared thermographic assessment of spinal anaesthesia-related cutaneous temperature changes during caesarean section.

INTRODUCTION: Assessment of adequacy of spinal anaesthesia, prior to obstetric surgery is extremely important but can be problematic because currently available clinical assessment methods are indirect and subjective. As the sympathectomy associated with spinal anaesthesia is known to cause vasodilation and heat redistribution, we sought to assess whether spinal anaesthesia led to significant and consistent cutaneous temperature changes as measured by infrared thermography. METHODS: Following ethics committee approval, this observational study was conducted in a tertiary level obstetric centre. Participants included women undergoing elective caesarean section under spinal anaesthesia. Following consent, a Flir T540 infrared camera captured thermographic images over the feet, patella, buttock, iliac crests, xiphisternum and axilla. Temperature was measured prior to spinal needle insertion (T0) and following clinical assessment when the block was deemed adequate. RESULTS: Thirty patients were included. Baseline temperature varied considerable by site. Spinal anaesthesia altered skin temperature in all areas of interest: right and left hallux (mean of differences (MD) +4.0°C and 5.2°C respectively, P <0.0001), right and left plantar (MD +6.1°C and 6.8°C respectively, P <0.0001), patella (MD -0.33°C, P=0.0445), buttock (MD -0.5°C, P=0.009), iliac crest (MD -0.7°C, P=0.0004), xiphisternum (MD -0.95°C, P <0.0001) and axilla (MD -0.71°C, P=0.0002). CONCLUSIONS: Following spinal anaesthesia thermographic imaging identified different patterns of skin temperature changes, with pronounced temperature increases measured in the feet and cooling of a lesser amplitude in the thoracic and lumbar dermatomes. Infrared thermography has the potential to provide objective measurement of sympathectomy.

Pegylated Bovine Carboxyhemoglobin (SANGUINATE) in a Jehovah's Witness Undergoing Liver Transplant: A Case Report.

Liver transplantation in practicing Jehovah's Witnesses is challenging because of their religious beliefs preventing them from accepting allogenic blood products. Pegylated bovine carboxyhemoglobin (SANGUINATE) is an oxygen transfer agent, currently under investigation for the treatment of sickle cell disease, which may play a role in these patients by maximizing perioperative oxygen delivery. We report a case involving the use of SANGUINATE in a Jehovah's Witness undergoing liver transplant.

Green discolouration of urine following propofol infusion in a dog.

A three-year-old, female neutered Weimaraner was presented with a history of neck pain and tetraparesis. MRI revealed an extradural mass at the level of C3 vertebra, which was thought to be a spinal abscess, and the dog was scheduled for surgical exploration the following morning. Overnight the dog developed an exaggerated ventilatory pattern, with paradoxical inward movement of the thorax on inspiration. Arterial blood gas analysis revealed respiratory acidosis and ventilator support was initiated to prevent excessive respiratory fatigue. During mechanical ventilation, anaesthesia was maintained using a propofol target-controlled infusion system and, subsequently, the dog produced bright green urine in the urine collection system. Although previously documented in humans, this appears to be the first report of green urine in a dog following propofol use.

Spectroscopic evidence for origins of size and support effects on selectivity of Cu nanoparticle dehydrogenation catalysts.

Selective dehydrogenation catalysts that produce acetaldehyde from bio-derived ethanol can increase the efficiency of subsequent processes such as C-C coupling over metal oxides to produce 1-butanol or 1,3-butadiene or oxidation to acetic acid. Here, we use in situ X-ray absorption spectroscopy and steady state kinetics experiments to identify Cuδ+ at the perimeter of supported Cu clusters as the active site for esterification and Cu0 surface sites as sites for dehydrogenation. Correlation of dehydrogenation and esterification selectivities to in situ measures of Cu oxidation states show that this relationship holds for Cu clusters over a wide-range of diameters (2-35 nm) and catalyst supports and reveals that dehydrogenation selectivities may be controlled by manipulating either.

Site-specific covalent capture of human O6-alkylguanine-DNA-alkyltransferase using single-stranded intrastrand cross-linked DNA.

A methodology is reported to conjugate human O6-alkylguanine-DNA-alkyltransferase (hAGT) to the 3'-end of DNA in excellent yields with short reaction times by using intrastrand cross-linked (IaCL) DNA probes. This strategy exploited the substrate specificity of hAGT to generate the desired DNA-protein covalent complex. IaCL DNA linking two thymidine residues, or linking a thymidine residue to a 2'-deoxyguanosine residue (either in a 5'→3' or 3'→5' fashion), lacking a phosphodiester linkage at the cross-linked site, were prepared using a phosphoramidite strategy followed by solid-phase synthesis. All duplexes containing the model IaCL displayed a reduction in thermal stability relative to unmodified control duplexes. The O4-thymidine-alkylene-O4-thymidine and the (5'→3') O6-2'-deoxyguanosine-alkylene-O4-thymidine IaCL DNA adducts were not repaired by any of the AGTs evaluated (human AGT and Escherichia coli homologues, OGT and Ada-C). The (5'→3') O4-thymidine-alkylene-O6-2'-deoxyguanosine IaCL DNA containing a butylene or heptylene tethers were efficiently repaired by the human variant, whereas Ada-C was capable of modestly repairing the heptylene IaCL adduct. The IaCL strategy has expanded the toolbox for hAGT conjugation to DNA strands, without requiring the presence of a complementary DNA sequence. Finally, hAGT was functionalized with a fluorescently-labelled DNA sequence to demonstrate the applicability of this conjugation method.

Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η.

DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O4-Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4-O4 bond on processing by human DNA polymerase η (hPol η) was studied for oligonucleotides containing O4-methylthymidine, O4-ethylthymidine, and analogs restricting the O4-methylene group in an anti-orientation. Primer extension assays revealed that the O4-alkyl orientation influences hPol η bypass. Crystal structures of hPol η•DNA•dNTP ternary complexes with O4-methyl- or O4-ethylthymidine in the template strand showed the nucleobase of the former lodged near the ceiling of the active site, with the syn-O4-methyl group engaged in extensive hydrophobic interactions. This unique arrangement for O4-methylthymidine with hPol η, inaccessible for the other analogs due to steric/conformational restriction, is consistent with differences observed for nucleotide incorporation and supports the concept that lesion conformation influences extension across DNA damage. Together, these results provide mechanistic insights on the mutagenicity of O4MedT and O4EtdT when acted upon by hPol η.

An evaluation of a target-controlled infusion of propofol or propofol-alfentanil admixture for sedation in dogs.

OBJECTIVES: To evaluate sedation quality and cardiorespiratory variables in dogs sedated using a target-controlled infusion of propofol or propofol-alfentanil admixture. METHODS: A total of 60 dogs undergoing diagnostic imaging were randomly assigned to one of three sedation protocols: propofol alone; propofol with a low concentration of 12 µg of alfentanil per mL of propofol; or propofol with a higher concentration of 24 µg of alfentanil per mL of propofol. Target-controlled infusion was initiated at a propofol target concentration of 1·5 µg/mL and increased until lateral recumbency was achieved. Times to adopt lateral recumbency and recover, pulse rate, respiratory rate, oscillometric mean arterial pressure and oxygen saturation were recorded. Quality of sedation onset and recovery were scored. RESULTS: Propofol target at lateral recumbency differed significantly (P=0·01) between groups with median (range) values of 3·0 (1·5 to 5·5), 2·0 (2 to 4·5) and 2·25 (1·5 to 3·5) µg/mL for propofol alone, propofol with the lower concentration of alfentanil and propofol with the higher concentration of alfentanil groups, respectively. Time to lateral recumbency was longer and quality of onset less smooth for the propofol group. Pulse rate change differed significantly (P<0·001) between groups (mean pulse rate change at onset of sedation: propofol group +2 ±24 bpm, low concentration alfentanil group -30 ±24 bpm, higher concentration alfentanil group -26 ±23 bpm). Hypoxaemia (SpO2 <90%) occurred in 1, 3 and 13 dogs, in the propofol group, the low concentration alfentanil group and the higher concentration of alfentanil group, respectively (P<0·001). CLINICAL SIGNIFICANCE: Addition of alfentanil to propofol target-controlled infusion did not confer cardiovascular benefits and, at the higher concentration, alfentanil increased the incidence of hypoxaemia.

A randomised controlled trial using the Epidrum for labour epidurals.

The aim of our study was to determine if using the Epidrum to site epidurals improves success and reduces morbidity. Three hundred parturients requesting epidural analgesia for labour were enrolled. 150 subjects had their epidural sited using Epidrum and 150 using standard technique. We recorded subject demographics, operator experience, number of attempts, Accidental Dural Puncture rate, rate of failure to site epidural catheter, rate of failure of analgesia, Post Dural Puncture Headache and Epidural Blood Patch rates. Failure rate in Epidrum group was 9/150 (6%) vs 0 (0%) in the Control group (P = 0.003). There were four (2.66%) accidental dural punctures in the Epidrum group and none in the Control group (P = 0.060), and 2 epidurals out of 150 (1.33%) in Epidrum group were re-sited, versus 3/150 (2%) in the control group (P = 1.000). The results of our study do not suggest that using Epidrum improves success or reduces morbidity.

Statistics: general linear models (a flexible approach).

This article moves on to discuss a type of statistical testing different from those we have discussed previously, namely a General Linear Model. This system incorporates a number of other statistical models and is a powerful tool used widely in modern statistics.