Acute exacerbation of COPD.

The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

The spectral-structural relationship of a series of oxyluciferin derivatives.

The absorption and emission spectra of a series of oxyluciferin derivatives with different substituents, as well as 6'-amino oxyluciferins in different enol and keto forms, with or without an active-site model of luciferase, were systematically investigated using density functional theory. The effects of substituents, microenvironment, and the luciferase on the structures, absorption spectra, and fluorescent emission were all taken into account. It was found that a wide range of emission colors can be obtained from various oxyluciferin derivatives with the inclusion of active site residues modeling the luciferase active site. Enol and keto forms are responsible for the emissions observed in experiments. It was suggested that the active site of luciferase must be included in the calculation in order to determine the form of the emitters.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Novel use of intrathecal baclofen drug delivery system for periodic focal dystonia in a teenager.

INTRODUCTION: Focal dystonia, often affecting part of a limb, is a manifestation of complex regional pain syndrome (CRPS). This can be difficult to diagnose and treat. Furthermore, there may be significant latency between the onset of dystonia after the diagnosis of CRPS. We present the case of a 15-year-old girl with periodic focal dystonia who has been successfully treated with an intrathecal baclofen pump. MATERIALS AND METHODS: The patient had sustained a minor ankle fracture four years prior to presentation. Despite radiologic evidence of adequate bony union, the patient continued to complain of spasms and pain in her left foot leading to dystonic posturing of the foot. Multiple therapies including subcutaneous morphine infusion, ankle splinting, physiotherapy, and local botulinum injections had not provided adequate relief. Intrathecal baclofen on three separate occasions resulted in successful temporary resolution of the dystonia. A placebo double-blinded injection of intrathecal saline at a separate setting however did not resolve the dystonia. RESULTS: We then proceeded with permanent delivery of baclofen by implantation of an intrathecal drug delivery pump, which resulted in resolution of the dystonia. The patient also was able to receive bolus doses of intrathecal baclofen. The patient is now able to partake in sporting and dancing activities. A detailed history of the patient, along with the difficulties in diagnosis and management, is presented. CONCLUSION: Intrathecal baclofen therapy can be effective in the management of focal dystonia after rigorous preoperative testing and counseling of adolescents with CRPS.

Anti-synthetase syndrome associated interstitial lung disease after combination dual immune checkpoint inhibition.

Immune checkpoint inhibitors (ICIs) unleash potent anti-tumour responses but with frequent off-target immune-mediated adverse events (irAE). ICIs can induce a spectrum of rheumatologic manifestations including inflammatory arthritis, Sjögren's syndrome, scleroderma and systemic lupus erythematosus. Here, we describe a case of antisynthetase syndrome associated interstitial lung disease (ILD) following dual Programmed Cell Death 1 and Cytotoxic T Lymphocyte-Associated Protein 4 checkpoint inhibition in a patient with metastatic melanoma. Initial treatment course was complicated by a number of irAEs including pneumonitis, colitis and thyroiditis. Suspicion of an underlying systemic rheumatic disease was heightened by the severe, relapsing and fibrosing nature of the interstitial pneumonitis. A diagnosis of amyopathic antisynthetase syndrome was made upon detection of circulating aminoacyl-tRNA synthetase (anti-EJ) autoantibodies. Intensification of induction immunosuppression followed by maintenance mycophenolate, prednisone and monthly intravenous immunoglobulin achieved long-term disease control. Detection of de novo ICI-induced inflammatory myositis ILD requires a high index of suspicion and carries important prognostic and treatment implications.

A Case of Portal Vein Thrombosis in a Patient With Methylenetetrahydrofolate Reductase A1298C Polymorphism.

Portal vein thrombosis (PVT) is a prothrombotic state caused by blood flow stasis, vascular injury, and/or hypercoagulability, resulting in partial or complete occlusion of the portal vein. PVT is a rare diagnosis, particularly among those without liver disease. Typical risk factors for PVT include cirrhosis, hepatocellular carcinoma, myeloproliferative neoplasms, other malignancies, oral contraceptive use, bowel infections, and inherited hypercoagulable disorders. The goal of this study is to analyze a case of PVT in a patient in which no clear etiology could be identified and to evaluate whether the patient's methylenetetrahydrofolate reductase (MTHFR) polymorphism may have been a risk factor. This is a case of a 44-year-old female with a history of irritable bowel syndrome, hypertension, hyperlipidemia, sleep apnea, gastric bypass surgery, and MTHFR polymorphism who presented to a walk-in clinic with five days of severe abdominal pain associated with diarrhea, nausea, and anorexia. Hypertension and tenderness over the right lower quadrant prompted a referral to the emergency department for evaluation of possible appendicitis. A contrasted computerized tomography (CT) scan of the abdomen and pelvis revealed a normal appendix and acute portal vein thrombosis. She was then admitted for treatment with intravenous (IV) heparin, fluids, and pain management. After an uneventful three-day hospital course, the patient was discharged on rivaroxaban with a plan to continue anticoagulation therapy for six months and follow up with a hematologist, who later confirmed the patient did not have any inherited hypercoagulable disorders. It is unclear whether the patient's MTHFR polymorphism prompted her PVT as existing data on MTHFR's effects are limited and conflicting. One cannot conclude that MTHFR caused a state of hyperhomocysteinemia to prompt hypercoagulability, as this has not been consistently proven in current literature, and the patient's homocysteine levels were not measured at the time of diagnosis. This case illustrates that further research on the various MTHFR polymorphisms and their effects on coagulation, potentially via homocysteinemia, is warranted. Further research on the MTHFR polymorphisms may help determine whether providers should test for MTHFR in the evaluation of thrombotic risk factors and may help optimize the treatment of thrombotic events for affected individuals.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.

Routine use of the Bath Adolescent Pain Questionnaire in a paediatric pain clinic.

INTRODUCTION: Assessment of outcomes from health interventions are of increasing importance, primarily to identify effective and safe treatment, but also to justify funding decisions. The Bath Adolescent Pain Questionnaire (BAPQ) is a self-report questionnaire, validated in 11-18 year olds, assessing the impact of pain in multiple domains of adolescent life. The similarly validated Bath Adolescent Pain Questionnaire for Parents (BAPQ-P) uses the same domains as the BAPQ, assessing the functioning and development of the adolescent from the parents' perspective. METHODS: We conducted a prospective study, planning to routinely collect BAPQ/BAPQ-P data at initial assessment and 6 months later. All patients aged between 5 and 19 attending our chronic pain clinic for the first time between December 2009 and December 2014 were mailed BAPQ and BAPQ-P questionnaires before the first appointment and 6 months after the first appointment. RESULTS: In total, 376 of 386 families returned questionnaires at time 0 and 96 after 6 months, 26% of those responded at time 0. We found statistically significant differences on patients' BAPQ questionnaires from 0 to 6 months showing improvement in all domains. A different result was found on parents' questionnaires where we only found a statistically significant difference on daily and emotional functioning. When comparing patient and parent questionnaires at 0 and 6 months, we found statistically significant differences between patients' and parents' questionnaires in the daily functioning and development domains. CONCLUSION: We believe BAPQ and BAPQ-P measurement proved useful tools to assess response to pain management input in adolescents over a 6-month period. Our experience and results suggest that these tools can, with appropriate administrative support, be used in routine clinical practice to assess patient outcomes. We also believe that BAPQ and BAPQ-P measurements have a utility to audit pain clinic activity and potentially a use in demonstrating beneficial outcomes to commissioners.

Performance of myositis-specific antibodies detected on myositis line immunoassay to diagnose and sub-classify patients with suspected idiopathic inflammatory myopathy, a retrospective records-based review.

AIM: To evaluate myositis line immunoassay (LIA) for diagnosis and sub-classification of suspected idiopathic inflammatory myopathy (IIM). To investigate if test performance is improved by increasing signal strength cut-off for myositis-specific antibody (MSA) or combining MSA with indirect immunofluorescence (IIF). METHODS: A retrospective, consecutive case series of patients investigated for MSAs from June 2013 to June 2020 for suspected IIM. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals for diagnosis of IIM. Association of IIM diagnosis with increased signal strength and presence of an expected IIF pattern on Hep-2 cells was assessed by Fisher's exact test in MSA-positive patients. RESULTS: A total of 195 patients were evaluated. IIM was diagnosed in 32/195 (16.4%) patients. MSAs were detected in 41/195 (21%) patients, 18/41 (43.9%) patients with an MSA had a diagnosis of IIM. The probability of an IIM diagnosis was increased in MSA-positive patients with high compared with low signal strength (83.3% vs 43.5%; P = 0.01) and an expected compared with unexpected IIF pattern (61.5% vs 23.8%; P = 0.04). Specificity for IIM was not significantly improved by increasing signal strength cut-off (85.9% vs 93.8%). Positive predictive value of myositis LIA was only modest and not significantly improved by either increasing signal strength cut-off or requiring an expected IIF pattern for determination of MSA positivity (43.9% vs 60% vs 61.5%). Sub-classification of IIM correlated closely for respective MSAs (88.9%). CONCLUSION: Increased MSA signal strength on myositis LIA and the presence of an expected IIF pattern were associated with IIM diagnosis. Test performance was non-significantly improved by these methods. Prevalence of IIM in this patient cohort was low; it is not excluded that LIA performance could be improved by these methods in a higher prevalence cohort.

Multiple Sleep Latency Test: when are 4 naps enough?

STUDY OBJECTIVES: The Multiple Sleep Latency Test (MSLT) is central to the diagnosis of narcolepsy and idiopathic hypersomnia. This study is the first to assess the impact of a 5-nap protocol on meeting MSLT-derived diagnostic criteria in a general cohort referred for MSLT, without selection bias. METHODS: Data for all MSLTs performed at 2 tertiary sleep units in Australia between May 2012 and May 2018 were retrospectively assessed for the impact of the fifth nap on mean sleep latency (MSL) and sleep onset rapid eye movement periods. RESULTS: There were 122 MSLTs included. The MSL was 8.7 ± 5.1 minutes after 4 naps, compared with 9.2 ± 5.2 minutes for 5 naps (P < .0001). In 8 cases, inclusion of the fifth nap changed the MSL to a value above the diagnostic threshold of 8 minutes. There were no instances in which the MSL moved to ≤ 8 minutes based on fifth nap data. A sleep onset rapid eye movement period occurred in the fifth nap in 9 patients and altered the interpretation in 2 cases. CONCLUSIONS: The fifth nap in an MSLT is associated with an increased MSL, although this difference is rarely clinically significant. In patients with borderline MSL or 1 sleep onset rapid eye movement period after 4 naps, a fifth nap can alter the outcome and should be performed. However, for many cases, a 4-nap MSLT protocol will suffice, potentially allowing resource savings without compromising diagnostic accuracy. We propose the adoption of a conditional 4-nap or 5-nap protocol based on specific criteria.

Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality: Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration.

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.

SERS of beta-thioglucose adsorbed on nanostructured silver electrodes.

Highly ordered microporous films of silver-containing regular arrays of spherical pores of differing diameters were prepared by electrochemical deposition into the interstitial spaces of a template formed by nanosphere lithography. These nanostructured electrodes in conjunction with a Raman microprobe spectrometer were used to obtain surface-enhanced Raman spectra (SERS) of beta-thioglucose (beta-TG) under potential control. The SERS results were compared with SERS of beta-TG on an electrochemically roughened silver electrode surface. The bands in the experimental spectra were assigned to particular vibrations with the help of ab initio predictions of the spectra. The results of this study show that beta-TG self-assembled at a silver electrode forms a hydrophilic film that may be used in biomimetic research to enhance interactions between the electrode and the hydrophilic portion of a model membrane, and to prevent interactions of proteins inserted into this membrane with the metal surface. However, in contact with the aqueous electrolyte an anomerization reaction takes place and the beta-TG film is a mixture of the alpha- and beta-anomers of thioglucose. A partial oxidation of the self-assembled molecules was also observed. In addition, the orientation of the adsorbed molecules changes as a function of the applied potential.

A time-dependent density functional theory investigation on the origin of red chemiluminescence.

Is the resonance-based anionic keto form of oxyluciferin the chemical origin of multicolor bioluminescence? Can it modulate green into red luminescence? There is as yet no definitive answer from experiment or theory. The resonance-based anionic keto forms of oxyluciferin have been proposed as a cause of multicolor bioluminescence in the firefly. We model the possible structures by adding sodium or ammonium cations and investigating the ground- and excited-state geometries as well as the electronic absorption and emission spectra. A role for the resonance structures is obvious in the gas phase. The absorption and emission spectra of the two structures are quite different--one in the blue and another in the red. The differences in the spectra of the models are small in aqueous solution, with all the absorption and emission spectra in the yellow-green region. The resonance-based anionic keto form of oxyluciferin may be one origin of the red-shifted luminescence but is not the exclusive explanation for the variation from green (approximately 530 nm) to red (approximately 635 nm). We study the geometries, absorption, and emission spectra of the possible protonated compounds of keto(-1) in the excited states. A new emitter keto(-1)'-H is considered.

Theoretical investigation on the origin of yellow-green firefly bioluminescence by time-dependent density functional theory.

The question whether the emitter of yellow-green firefly bioluminescence is the enol or keto-constrained form of oxyluciferin (OxyLH(2)) still has no definitive answer from experiment or theory. In this study, Arg220, His247, adenosine monophosphate (AMP), Water324, Phe249, Gly343, and Ser349, which make the dominant contributions to color tuning of the fluorescence, are selected to simulate the luciferase (Luc) environment and thus elucidate the origin of firefly bioluminescence. Their respective and compositive effects on OxyLH(2) are considered and the electronic absorption and emission spectra are investigated with B3LYP, B3PW91, and PBE1KCIS methods. Comparing the respective effects in the gas and aqueous phases revealed that the emission transition is prohibited in the gas phase but allowed in the aqueous phase. For the compositive effects, the optimized geometry shows that OxyLH(2) exists in the keto(-1) form when Arg220, His247, AMP, Water324, Phe249, Gly343, and Ser349 are all included in the model. Furthermore, the emission maximum wavelength of keto(-1)+Arg+His+AMP+H(2)O+Phe+Gly+Ser is close to the experimental value (560 nm). We conclude that the keto(-1) form of OxyLH(2) is a possible emitter which can produce yellow-green bioluminescence because of the compositive effects of Arg220, His247, AMP, Water324, Phe249, Gly343, and Ser349 in the luciferase environment. Moreover, AMP may be involved in enolization of the keto(-1) form of OxyLH(2). Water324 is indispensable with respect to the environmental factors around luciferin (LH(2)).

Predictions of the fluorine NMR chemical shifts of perfluorinated carboxylic acids, CnF(2n+1)COOH (n = 6-8).

Perfluorinated carboxylic acids (PFCAs) are a class of persistent environmental pollutants. Commercially available PFCAs are mixtures of linear and branched isomers, possibly with impurities. Different isomers have different physical and chemical properties and toxicities. However, little is known about the properties and the finer details of the structures of the individual branched isomers. Full geometry optimizations for the linear n-alkane (C(6)-C(27)) PFCAs indicated that all have helical structures. The helical angle increases slightly with increasing chain length, from 16.3 degrees in C(6)F(13)COOH to 17.0 degrees in C(27)F(55)COOH. This study predicts (19)F NMR parameters for 69 linear and branched isomers of the perfluoro carboxylic acids C(6)F(13)COOH, C(7)F(15)COOH, and C(8)F(17)COOH. B3LYP-GIAO/6-31++G(d,p)//B3LYP/6-31G(d,p) was used for the NMR calculations with analysis of the chemical shifts by the natural bond orbital method. The predictions of the (19)F chemical shifts revealed the differences among the CF(3), CF(2), and CF groups. In general, the absolute values for the chemical shifts for the CF(3) group are smaller than 90 ppm, for the CF larger than 160 ppm, and for the CF(2) between 110 and 130 ppm. The chemical shifts of the branched isomers are smaller in magnitude than the linear ones. The decrease is correlated with the steric hindrance of the CF(3) groups, the more hindered the CF(3), the greater the decrease in the (19)F chemical shifts. The predicted (19)F chemical shifts are similar to those for analogous perfluoro compounds with other terminal functional groups such as -SO(3)H or -SO(3)NH(2)CH(2)CH(3).

Movement disorders associated with complex regional pain syndrome in children.

The aim of the present study was to review the history, clinical course, treatment, and outcome of movement disorders in children and young people with complex regional pain syndrome (CRPS). Case notes were reviewed retrospectively of children and young people who presented with movement disorders in CRPS to our tertiary paediatric pain service over a period of 13 years. Ten children with CRPS presented with movement disorders (eight females, two males). The age at first presentation with symptoms of CRPS ranged from 8 to 15 years (mean 11 y 2 mo, median 13 y). The most common movement disorder was dystonia (n=8), followed by tremors (n=3) and myoclonus (n=3); two patients had all three movement disorders. The movement disorder affected mainly the lower limb (n=9) with a predilection for the foot (n=7) and was frequently initiated by minor trauma (n=7). Follow-up ranged from 6 months to 14 years. The outcome was variable, with good prognosis in nearly half of the cases: four children experienced complete resolution of symptoms. Two children showed a slight improvement. Four children showed no improvement. Movement disorders in CRPS are under-recognized in children. The management has to be multidisciplinary with an expertise in paediatric pain.

Recent experience with the neuromonics tinnitus treatment.

This study examines the outcomes of patients undergoing the Neuromonics tinnitus treatment protocol at a single, tertiary referral center over a 2-year period. A retrospective review of patient records was performed with the objective of collecting demographic and au-diological information and identifying changes in score on an established tinnitus questionnaire (Tinnitus Reaction Questionnaire [TRQ]) after treatment. Forty-seven patients initiated reatment with the Neuromonics device during the study period. Fourteen patients completed treatment, and another 18 were actively undergoing treatment at the end of the study period. The mean pure-tone average for the study group (N = 47) was 23.4 dB for the involved ear. Of those who completed the treatment, the mean posttreatment TRQ score was significantly lower than the pretreatment score (p approximately .001). Fifteen patients (31.9%) returned the device or did not complete treatment. Across all 47 patients, 48.9% achieved a successful reduction of 40% or greater in TRQ score. There was no correlation among pure-tone average, initial TRQ score or duration of use, and percentage change in TRQ score for those with at least one follow-up test. Based on these preliminary findings, treatment with the Neuromonics device is successful in reducing TRQ scores in appropriately selected patients with tinnitus.

Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury.

Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal's canal (RC), perilymph, or endolymph of Mongolian gerbils either 1-3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.

Color-tuning mechanism in firefly luminescence: theoretical studies on fluorescence of oxyluciferin in aqueous solution using time dependent density functional theory.

The first singlet excited state geometries of various isomers and tautomers of firefly oxyluciferin (OxyLH2), as well as their fluorescence spectra in aqueous solution, were studied using time dependent density functional theory (TDDFT). With changing pH in aqueous solution, three fluorescence peaks, blue (450 nm), yellow-green(560 nm), and red (620 nm) correspond to neutral keto and enolic forms, the monoanionic enolic form,and the monocationic keto form respectively. A counterion, Na+, was predicted to cause a blue shift in the fluorescence of anionic OxyLH2. The contributions of a charge transfer (CT) state upon electronic excitation of the planar and twisted structures were predicted. CT was large for the twisted structures but small for the planar ones. The differences between pK and pK* of various oxyluciferin species were predicted using a Forster cycle. A new possible light emitter, namely, the monocation keto form (keto+1), was considered.

Effects of endoscopic sinus surgery and delivery device on cadaver sinus irrigation.

OBJECTIVE: Assess paranasal sinus distribution of topical solutions following endoscopic sinus surgery (ESS) using various delivery devices. STUDY DESIGN: Experimental prospective study. SUBJECTS AND METHODS: Ten cadaver sinus systems were irrigated with Gastroview before surgery, after ESS, and after medial maxillectomy. Delivery was via pressurized spray (NasaMist), neti pot (NasaFlo), and squeeze bottle (Sinus Rinse). Scans were performed before and after each delivery with a portable CT machine (Xoran xCAT), and blinded assessments were made for distribution to individual sinuses. RESULTS: Total sinus distribution was greater post-ESS (P < 0.001). Additional distribution was gained with medial maxillectomy (P = 0.02). Influence of delivery device on distribution was significantly higher with neti pot > squeeze bottle > pressurized spray (P < 0.001). Frontal sinus penetration was greatest after surgery (P = 0.001). CONCLUSION: ESS greatly enhances the delivery of nasal solutions, regardless of delivery device. Pressurized spray solutions in un-operated sinuses provide little more than nasal cavity distribution. Use of squeeze bottle/neti pot post-ESS offers a greatly enhanced ability to deliver solutions to the paranasal sinuses.