Proximie in the operating theatre: evaluation of a virtual operating platform for medical student education.

INTRODUCTION: Medical students often hesitate to enter the operating theatre because of poor visibility of the surgical field and anxiety about the theatre environment. In addition, ear, nose and throat (ENT) surgery is underrepresented in many medical curricula. Virtual systems like Proximie offer flexible viewing of surgeries with surgeon commentary, potentially addressing these issues. METHODS: This descriptive survey study aimed to evaluate the use of Proximie as a surgical education tool for delivering ENT teaching to medical students. Live ENT procedures were recorded at the ENT Department of the John Radcliffe Hospital and shared with interested clinical medical students through Proximie accounts. Students were added to a private group chat to ask questions and provided feedback through structured forms, assessing procedural effectiveness and the platform's technology. Live-streaming and recording of procedures were facilitated by ENT surgeons providing commentary. RESULTS: Conducted over four virtual theatre days, the study gathered 52 responses: 96% of students rated Proximie's educational value as 4 of 5 or higher; 57% preferred the virtual experience over physical attendance because of its convenience and the improved view of the surgical field. Students valued the live commentary and showed interest in using Proximie for a broader range of surgeries. Suggested improvements included fixing technical issues, better communication of theatre lists, and expanding surgical specialty coverage. CONCLUSIONS: Proximie has been highly rated by medical students for its effective and engaging approach in the instruction of surgical skills, underscoring its value as an educational tool. Future research is needed to formally assess knowledge acquisition and retention across multiple surgical subspecialties. This work is the first step towards evaluating the utility of virtual operating theatre platforms for medical student education.

Characteristics, management and outcome of a large necrotising otitis externa case series: need for standardised case definition.

BACKGROUND: Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines. METHOD: This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre. RESULTS: A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23-121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016). CONCLUSION: A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.

Characterization of imine reductases in reductive amination for the exploration of structure-activity relationships.

Imine reductases (IREDs) have shown great potential as catalysts for the asymmetric synthesis of industrially relevant chiral amines, but a limited understanding of sequence activity relationships makes rational engineering challenging. Here, we describe the characterization of 80 putative and 15 previously described IREDs across 10 different transformations and confirm that reductive amination catalysis is not limited to any particular subgroup or sequence motif. Furthermore, we have identified another dehydrogenase subgroup with chemoselectivity for imine reduction. Enantioselectivities were determined for the reduction of the model substrate 2-phenylpiperideine, and the effect of changing the reaction conditions was also studied for the reductive aminations of 1-indanone, acetophenone, and 4-methoxyphenylacetone. We have performed sequence-structure analysis to help explain clusters in activity across a phylogenetic tree and to inform rational engineering, which, in one case, has conferred a change in chemoselectivity that had not been previously observed.

Electron localisation in static and time-dependent one-dimensional model systems.

The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

Surface rearrangement of adsorbed EGCG-mucin complexes on hydrophilic surfaces.

The kinetic adsorption-desorption behaviour of porcine gastric mucin in the presence of physiologically relevant concentrations of the polyphenol epigallocatechin gallate (EGCG) was investigated using high-resolution kinetic optical waveguide lightmode spectroscopy (OWLS) and atomic force microscopy (AFM). Comparison with dynamic light scattering results from EGCG-mucin mixtures indicates that discrete particles are formed whose size increases with increasing EGCG:mucin ratio. These particles are deduced to be the adsorbing entities, which fuse on the surface to form complex surface layers. At low molar EGCG:mucin ratios (<∼1000), aggregates fuse on the surface to form a monolayer similar to one of pure mucin. With increasing EGCG concentration, the surface assembly of aggregates becomes consistent with their rearrangement and spreading in the shape of a spherical segment. At the highest molar ratios investigated (>12,000) the particles begin to destabilize. The presence of EGCG leads to birefringence hysteresis during adsorption-desorption, indicating structural rearrangement, even at molar ratios ∼1000. The intensification of the phenomenon with increasing EGCG:mucin ratio mimics what was previously observed with the increase of mucin concentration in an EGCG-free system.

Controversies in the management of caustic ingestion injury: an evidence-based review.

BACKGROUND: Caustic ingestion of acid or alkaline substances can cause damage to the upper respiratory and upper digestive tract. Initial presentation following caustic ingestion can include oropharyngeal pain, dysphagia and stridor. It is due to this clinical presentation that the resident otolaryngologist is consulted to review and examine these patients to assess for airway compromise and commence initial management and care until airway concern has passed. OBJECTIVE OF REVIEW: This review aims to provide evidence-based guidance in the management of those presenting with acute ingestion injury so that informed initial medical therapy can be commenced and appropriate investigations are arranged to optimize patient outcome. TYPE OF REVIEW AND SEARCH STRATEGY: A literature review searched PubMed citing variations on the areas of controversies with 'caustic ingestion', 'corrosive ingestion', 'acid ingestion' and 'alkali ingestion' - from 1956 to present with language restrictions. EVALUATION METHOD: The bibliographies of articles were searched for relevant references. The references were then compiled and reviewed independently by two authors (JB and SK), overseen by the senior authors (CP and JR). The review process was conducted independently, with the results then collated, with the aim of identifying the highest levels of evidence in each of the areas of controversy. RESULTS: Over 100 full-text articles were retrieved. Several specific areas of controversy were identified and addressed, with the highest available evidence referenced for each area. CONCLUSIONS: In caustic ingestion injury, the urgent assessment of the airway is the first priority with a definitive airway secured in those with airway compromise. In those patients with a stable airway and no clinical or radiological sign of perforation, then medical therapy should be commenced and an urgent oesophagogastroduodenoscopy (OGD) is arranged and this should take place within the first 24 h to grade the degree of injury and establish long-term prognosis. In suspected perforation, a surgical opinion should be sought. For those adults who are asymptomatic following ingestion an OGD may not be necessary; however, asymptomatic paediatric patients should be treated with more caution and a period of observation is important. Those who are at risk of developing late complications must be followed up.

Pete's bar: alternative use of the laryngoscopy suspension bar to improve surgical exposure during small incision cochlear implantation.

BACKGROUND: Cochlear implant surgery is increasingly being performed through a small incision because of the benefits associated with this technique, such as fewer wound complications. Efforts have been made to maximise surgical exposure in order to improve this evolving technique; this includes the development and use of new retractors. For instance, elasticated stay hooks can retract skin in a radial fashion and they are less bulky than traditional retractors. These hooks are usually attached directly to surgical drapes or to a disposable retractor ring; there are disadvantages to both of these methods. METHOD: This paper describes a technique using a laryngeal suspension bar in which the bar acts as a fixed structure to which these elasticated stay hooks can be attached. CONCLUSION: This technique was found to be safer, cheaper and more effective for obtaining optimal surgical exposure compared with a technique whereby the stay hooks are attached directly to the drapes or to a disposable retractor ring.

A UK experience of daycase cochlear implant surgery.

OBJECTIVES: This study aims to assess the safety of daycase cochlear implant surgery. METHODS: A retrospective review was conducted on all patients who underwent cochlear implant surgery at a teaching hospital in Oxford, UK between September 2008 and February 2012. RESULTS: One hundred and sixteen patients underwent cochlear implant surgery. This included 73 adults and 43 children. Twenty-six patients underwent the procedure as a daycase procedure. There were no readmissions. DISCUSSION: The demand 'to do more with less' has led to increasing drives for efficiency and cost-effectiveness. Therefore, the role of daycase surgery is becoming increasingly widespread. Daycase surgery has been shown to be advantageous for both patients and hospitals. CONCLUSION: Daycase cochlear implant surgery is feasible and can be safely conducted in a select group of patients.

Are UK otorhinolaryngologists maintaining their research output?

BACKGROUND: In the general surgical and anaesthetic literature, there has been a decline in research output originating from the UK. This study analysed the 10 globally leading and 2 UK leading otorhinolaryngology journals to determine whether this trend was also reflected within otorhinolaryngology. METHODS: Citable research output was analysed from 4 individual years, over a 10-year period (2000-2010), to determine absolute output, geographical mix and article type. RESULTS: The proportion of research output from the UK and Ireland grew 22.8 per cent among the leading global otorhinolaryngology journals, but fell 28.6 per cent among the leading two UK otorhinolaryngology journals. The converse trend was true for the USA and Canada. Output from European and the rest of the world grew among both sets of journals, while Japanese output fell. 'Research' articles remained the most prevalent type. CONCLUSION: These results are encouraging as they refute the fall in UK research output observed by other authors. In the face of growing challenges, it is important to maintain published output so that the fate that has befallen other specialties is not mirrored within UK otorhinolaryngology.

Exact density-functional potentials for time-dependent quasiparticles.

We calculate the exact Kohn-Sham potential that describes, within time-dependent density-functional theory, the propagation of an electron quasiparticle wave packet of nonzero crystal momentum added to a ground-state model semiconductor. The potential is observed to have a highly nonlocal functional dependence on the charge density, in both space and time, giving rise to features entirely lacking in local or adiabatic approximations. The dependence of the nonequilibrium part of the Kohn-Sham electric field on the local current and charge density is identified as a key element of the correct Kohn-Sham functional.

Investigation prior to thyroglossal duct cyst excision.

INTRODUCTION: Investigation of the anterior midline neck lump has been debated over the years with little agreement on best practice. Thyroglossal duct cysts (TDCs) are the most common aetiology. A TDC may contain ectopic thyroid tissue, which may affect the decision to excise. METHODS: A computerised survey was sent to a representative sample of UK-based ENT surgeons to determine current practice in investigation of presumed TDCs and the incidence of ectopic thyroid tissue. RESULTS: Overall, 95% of those surveyed use ultrasonography, with 32% also arranging thyroid function tests. Fifteen per cent had encountered absent normal thyroid tissue in the presence of a midline neck swelling. In 64% of cases this represented the only functioning thyroid tissue. Thyroid function tests were normal in all but two cases. CONCLUSIONS: The results show a significant change in practice over the last decade. All surgeons would arrange some form of investigation of a presumed TDC, with the vast majority using ultrasonography. Radioisotope scanning should only be used if the ultrasonography or thyroid function tests are abnormal. The incidence of ectopic thyroid tissue in this survey was higher than previously calculated, with a 0.17% prevalence of midline neck lumps representing the only functioning thyroid tissue.

Susac syndrome: outcome of unilateral cochlear implantation.

OBJECTIVE: Susac syndrome comprises a triad of vestibulocochlear dysfunction, retinopathy and multifocal encephalopathy, which is characterised pathophysiologically by microangiopathy of the ear, retina and brain. Diagnosis is confirmed by magnetic resonance imaging of the brain and ophthalmological examination, which reveals branch retinal artery occlusion. Hearing loss persists in 90 per cent of patients. We present a case of successful hearing rehabilitation by cochlear implantation in a young woman with this syndrome. CLINICAL PRESENTATION: A 36-year-old woman presented with neurological symptoms suggestive of encephalitis. She subsequently developed vestibulocochlear symptoms. The diagnosis was confirmed upon magnetic resonance imaging and fluorescein angiography, which showed multiple peripheral retinal arterial occlusions. Hearing loss was fluctuant but gradually progressive over nine months, to bilateral profound sensorineural hearing loss. INTERVENTION: A left cochlear implant was placed, with a good outcome. CONCLUSION: In this Susac syndrome patient, the outcome of cochlear implantation was encouraging, notwithstanding the possible involvement of retrocochlear pathways.

S-nitrosylation decreases the adsorption of H-Ras in lipid bilayer and changes intrinsic catalytic activity.

Structural, chemical, and mutational studies have shown that C-terminal cysteine residues on H-Ras could potentially be oxidized by nitrosylation. For investigating the effect of nitrosylation of Ras molecule on the adsorption of farnesylated H-Ras into lipid layer, experiments with optical waveguide lightmode spectroscopy were used. The analysis of association/dissociation kinetics to planar phospholipids under controlled hydrodynamic conditions has shown that preliminary treatment of protein by S-nitroso-cysteine decreased the adsorption of farnesylated H-Ras. The authors have found that compared with nitrosylated forms, farnesylated H-Ras has more compact configuration, because of the smaller area occupied by protein upon absorption at the membrane. The association rate coefficient for unmodified H-Ras was lower than similar parameter for farnesylated and nitrosylated forms. However, the desorbability, i.e., parameter, which reflects the rate of dissociation of protein from lipids is higher for farnesylated H-Ras. In addition, it was have found that farnesylation of cytoplasmic H-Ras, in contrast to membrane-derived forms, inhibits intrinsic GTPase activity of protein, and preliminary treatment of H-Ras by S-nitroso-cysteine restores the activity to the control level. These data suggest that nitrosylation of H-Ras rearranges the adsorptive potential and intrinsic GTPase activity of H-Ras through modification of C-terminal cysteines of molecule.

Multiple effects of childhood deafness on cortical activity in children receiving bilateral cochlear implants simultaneously.

OBJECTIVE: Auditory development is disrupted without normal hearing but might proceed to some extent depending on the type and onset of deafness. We therefore hypothesized that activity in the auditory cortex would be highly variable in children who are deaf. METHODS: To answer this, activity in the deaf brain was evoked by electrical pulses from newly provided bilateral cochlear implants (CIs) in 72 children (n=144 responses). RESULTS: Responses were categorized by visual inspection into 3 main types which were validated by principal component cluster analyses; 49% had a negative amplitude wave similar to that previously reported in pre-term infants, 26% were dominated by a positive peak typical of responses in young normal hearing children and experienced paediatric CI users, 25% were novel multi-peaked responses. No significant demographic differences, including duration and onset of deafness, were found between response types. However, children with severe biallelic mutations of GJB-2 showed predominately negative peak type responses (79%) as compared with their peers without these mutations who had a more equal distribution between cortical response types. CONCLUSION: Cortical development in children who are deaf is heterogeneous but can be better predicted when the genotype is known to be a GJB-2 mutation. SIGNIFICANCE: Remediation of childhood deafness seeks to restore normal development and function of central auditory functions and thus may need to be tailored to account for effects specific to the aetiology of deafness.

Langerhans' cell histiocytosis of the temporal bone: successful treatment of sensorineural hearing loss with low-dose radiotherapy.

OBJECTIVE: To present the successful treatment of sensorineural hearing loss secondary to Langerhans' cell histiocytosis with low-dose radiotherapy, and also the disparity between radiological resolution of Langerhans' cell histiocytosis lesions and lack of sensorineural hearing loss improvement, accompanied by a review of the literature on otolaryngological manifestations and management of Langerhans' cell histiocytosis. CASE REPORT: Langerhans' cell histiocytosis is a multisystem disease which frequently causes osseous lesions in the temporal bones. Hearing loss is usually conductive but may be sensorineural with lesions of the petrous temporal bone. We present a case of sensorineural hearing loss secondary to Langerhans' cell histiocytosis affecting the labyrinth and internal auditory meatus, which resolved following radiotherapy. Contralateral sensorineural hearing loss in the same patient, previously treated with chemotherapy, did not resolve despite radiological resolution of the temporal bone lesions. CONCLUSION: We suggest that timely radiotherapy for treatment of sensorineural hearing loss secondary to Langerhans' cell histiocytosis is an appropriate treatment option.

DBT degradation enhancement by decorating Rhodococcus erythropolis IGST8 with magnetic Fe3O4 nanoparticles.

Biodesulfurization (BDS) of dibenzothiophene (DBT) was carried out by Rhodococcus erythropolis IGST8 decorated with magnetic Fe3O4 nanoparticles, synthesized in-house by a chemical method, with an average size of 45-50 nm, in order to facilitate the post-reaction separation of the bacteria from the reaction mixture. Scanning electron microscopy (SEM) showed that the magnetic nanoparticles substantially coated the surfaces of the bacteria. It was found that the decorated cells had a 56% higher DBT desulfurization activity in basic salt medium (BSM) compared to the nondecorated cells. We propose that this is due to permeabilization of the bacterial membrane, facilitating the entry and exit of reactant and product, respectively. Model experiments with black lipid membranes (BLM) demonstrated that the nanoparticles indeed enhance membrane permeability.

Inhibition of nitric oxide synthase and farnesyltransferase change the activities of several transcription factors.

Several types of cellular proteins can be modified by farnesylation and nitrosylation, of which the most significant is Ras. We used manumycin, a farnesyltransferase inhibitor, and L-NAME (Nomega-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor, for characterization of Ras-dependent downstream targets activities. Our results suggest that change of the steady-state levels of nitric oxide and inhibition of farnesylation modified the activities of several transcription factors. We have found that the inhibition of farnesylation by manumycin decreased the DNA-binding activity of nuclear factor (NF)-kappaB, did not change the DNA-binding activities of STAT, Sp1, ATF-2, and CREB, and increased the activities of c-Fos, JunD, and c-Jun. Under such conditions, phosphorylation of Akt was decreased, whereas phosphorylation of extracellular signal-regulated kinase (ERK) was increased and phosphorylation of JNK did not change. Furthermore, our results show that reduction of intracellular concentration of nitric oxides by L-NAME increases the activities of c-Fos, ATF-2 and JunD and decreases the activities of CREB, STAT, Sp1, and c-Jun. The activities of all of these transcription factors are restored to normal levels in the presence of manumycin, suggesting that simultaneous modifications of proteins by farnesylation and nitrosylation change the direction of Ras-controlled downstream pathways. Our results provide further evidence of the significance of posttranslational modifications of Ras for the specificity of transducing cascade networks and physiological outcome.

Interfacial water structure controls protein conformation.

A phenomenological theory of salt-induced Hofmeister phenomena is presented, based on a relation between protein solubility in salt solutions and protein-water interfacial tension. As a generalization of previous treatments, it implies that both kosmotropic salting out and chaotropic salting in are manifested via salt-induced changes of the hydrophobic/hydrophilic properties of protein-water interfaces. The theory is applied to describe the salt-dependent free energy profiles of proteins as a function of their water-exposed surface area. On this basis, three classes of protein conformations have been distinguished, and their existence experimentally demonstrated using the examples of bacteriorhodopsin and myoglobin. The experimental results support the ability of the new formalism to account for the diverse manifestations of salt effects on protein conformation, dynamics, and stability, and to resolve the puzzle of chaotropes stabilizing certain proteins (and other anomalies). It is also shown that the relation between interfacial tension and protein structural stability is straightforwardly linked to protein conformational fluctuations, providing a keystone for the microscopic interpretation of Hofmeister effects. Implications of the results concerning the use of Hofmeister effects in the experimental study of protein function are discussed.

Production of homocysteine in serum-starved apoptotic PC12 cells depends on the activation and modification of Ras.

PC12 pheochromocytoma cells expressing a dominant inhibitory mutant of Ha-Ras (M-M17-26) and PC12 cells transfected with normal c-RasH (M-CR3B) have been used to investigate the role of nitrosylation and farnesylation of Ras on the production of homocysteine and the activities of the redox-sensitive transcription factors NF-kappaB and c-Fos. We found that under serum and nerve growth factor withdrawal conditions undifferentiated apoptotic M-CR3B cells accumulated more homocysteine than M-M17-26 cells, and the production of homocysteine decreased in the presence of manumycin and increased in the presence of l-NAME. Furthermore, we have shown that manumycin increased the activity of c-Fos in the M-CR3B cells and decreased the activity of NF-kappaB, while l-NAME decreased the activities of both transcription factors, and accelerated apoptosis of M-CR3B cells. In contrast, in M-M17-26 cells manumycin did not change the activity of c-Fos, nor the activity of NF-kappaB. We conclude that trophic factor withdrawal stimulates Ras, which apparently through the Rac/NADPH oxidase system induces permanent oxidative stress, modulates the activities of NF-kappaB and c-Fos, induces production of homocysteine and accelerates apoptosis. Nitrosylation of Ras is necessary for maintaining the survival of PC12 cells, while farnesylation of Ras stimulates apoptosis under withdrawal conditions.