Going where other methods cannot: A systematic mapping review of 25 years of qualitative research in Otolaryngology.

OBJECTIVE: To map the use of qualitative methods within otolaryngology, providing examples and identifying gaps in the literature. DESIGN: Systematic mapping review of journal-based literature from 1990 to 2015 using Medline, Embase, PsycINFO and CENTRAL. Included studies were categorised according to clinical subspecialty, research aims and qualitative approach. RESULTS: Of 4,061 identified articles, 388 were deemed relevant to qualitative research in ENT. The number of qualitative publications has risen markedly over the last 25 years (r = 0.802), particularly since 2010. The most commonly used method was semi-structured interviews 62.1% (241/388). Head and neck cancer (41.8% (162/388)) and otology (40.2% (156/388)) publish more qualitative research than rhinology (7.0% (27/388)) and laryngology (6.7% (26/388)). CONCLUSIONS: Qualitative research in otolaryngology has increased over time, but laryngology and rhinology remain under-represented. Most studies use interviews, underutilising the strengths of other qualitative methods. There is considerable scope for further application of qualitative methods in otolaryngology.

Bile acids: a potential role in the pathogenesis of pharyngeal malignancy.

OBJECTIVE: Gastro-oesophageal reflux disease is thought to be a risk factor for head and neck malignancies. Bile acids are one of the principle components of gastric refluxate and have previously been implicated in the development of oesophageal and bowel malignancies. There is clear evidence that bile acids reflux into the laryngopharynx. Despite this, the carcinogenic properties of bile acids in this area are yet to be fully identified. We therefore investigated the potential role of bile acids in pharyngeal malignancy, through the highly conserved process of epithelial-mesenchymal transition (EMT). EMT occurs in invasion and metastasis and is a central process in the development of epithelial carcinoma. DESIGN: Translational research study. METHODS: Human hypopharyngeal squamous carcinoma FaDu cells were challenged with primary (cholic or chenodeoxycholic) and secondary (deoxycholic or lithocholic) bile acids. EMT-relevant proteins TGF-ß1 and MMP-9 were measured in the cell culture supernates at 48 h via ELISA. Cell viability was confirmed >95% via CellTiter-Blue assay. RESULTS: Significantly greater concentrations of TGF-ß1 were measured in the culture supernates of cells treated with cholic acid, deoxycholic acid and chenodeoxycholic acid. MMP-9 levels were increased in deoxycholic acid and lithocolic acid stimulations when compared to control (P < 0.05). CONCLUSION: This is the first demonstration that bile acids induce TGF-ß1 and MMP-9 in pharyngeal cells. TGF-ß1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets.

Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE.

INTRODUCTION: Routine cognitive screening for in-patients aged ≥75 years is recommended, but there is uncertainty around how this should be operationalised. We therefore determined the feasibility and reliability of the Abbreviated mental test score (AMTS/10) and its relationship to subjective memory complaint, Montreal Cognitive Assessment (MoCA/30) and informant report in unselected older admissions. METHODS: Consecutive acute general medicine patients aged ≥75 years admitted over 10 weeks (March-May 2013) had AMTS and a question regarding subjective memory complaint (if no known dementia/delirium). At ≥72 h, the 30-point Montreal Cognitive Assessment (MoCA) and Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were done. Cognitive impairment was defined as AMTS < 9 or MoCA < 26 (mild impairment) and MoCA < 20 (moderate/severe impairment) or IQCODE ≥ 3.6. RESULTS: Among 264 patients (mean age/SD = 84.3/5.6 years, 117 (44%) male), 228 (86%) were testable with AMTS. 49/50 (98%) testable patients with dementia/delirium had low AMTS compared with 79/199 (44%) of those without (P < 0.001). Subjective memory complaint agreed poorly with objective cognitive deficit (39% denying a memory problem had AMTS < 9 (kappa = 0.134, P = 0.086)) as did informant report (kappa = 0.18, P = 0.15). In contrast, correlation between AMTS and MoCA was strong (R2 = 0.59, P < 0.001) with good agreement between AMTS < 9 and MoCA < 20 (kappa = 0.50, P < 0.01), although 85% of patients with normal AMTS had MoCA < 26. CONCLUSIONS: The AMTS was feasible and valid in older acute medicine patients agreeing well with the MoCA albeit with a ceiling effect. Objective cognitive deficits were prevalent in patients without known dementia or delirium but were not reliably identified by subjective cognitive complaint or informant report.

Pulsed ultrasound modulated optical tomography utilizing the harmonic response of lock-in detection.

Ultrasound modulated optical tomography (USMOT) can image the optical properties of a scattering medium at a spatial resolution approaching that of ultrasound (US). A lock-in parallel speckle detection technique is proposed to detect pulsed US modulated light using a multipixel detector. The frequency components of the pass band match those of the US pulse train and provide efficient detection. The modulation depth is extracted by taking the difference between a pair of speckle patterns modulated by a pair of phase-inversed US bursts. Modification to pulse inversion mode enables the second harmonic US modulation due to nonlinear US propagation to be detected.

Otitis externa: what is the problem with getting it right? A mixed-methods study in primary and secondary care.

OBJECTIVE: Otitis externa accounts for 1.1-1.3 per cent of patient presentations in primary care and 25 per cent of urgent referrals to ENT. This study aimed to explore otitis externa clinical decision-making at the primary-secondary care interface, otitis externa prevalence and recent trends in antimicrobial resistance in otitis externa related bacterial isolates and ototopical prescribing. METHOD: This is a mixed-methods study drawing on data from primary and secondary care and open National Health Service sources. RESULTS: A total of 101 general practitioner survey respondents reported frequently prescribing oral antibiotics for otitis externa. General practitioner consultations for otitis externa increased 25 per cent over 15 years. General practitioner ototopical preparations cost the National Health Service £7 410 440 in 2006 and £11 325 241 in 2016. A total of 162 consecutive hospital otitis externa-related bacterial isolates yielded 128 pseudomonas species, with 18 that were resistant to gentamicin and 7 that were resistant to ciprofloxacin. Ten guidelines reviewed showed systematic inconsistencies. CONCLUSION: General practitioners reported regularly prescribing oral antibiotics for otitis externa. Antimicrobial drug resistance is common in otitis externa. The available guidance is suboptimal.

Diversity in destinations, routes and timing of small adult and sub-adult striped bass Morone saxatilis on their southward autumn migration.

Almost three-quarters of the 46 young adult and sub-adult striped bass Morone saxatilis that were acoustically tagged in Plum Island Estuary, Massachusetts, U.S.A., in the summer of 2006 were detected in one or more southern coastal arrays during their autumn migration. On the basis of the trajectories along which these M. saxatilis moved from feeding to overwintering areas, three migratory groups emerged. After leaving Plum Island Estuary, about half of the fish were detected only in a mid-latitude array, Long Island Sound. The other half of the tagged fish were detected during autumn and winter in a more southern array, the Delaware Estuary. This latter group of fish may have used two routes. Some travelled to the Delaware Estuary through Long Island Sound while other fish may have taken a second, more direct, coastal route that did not include Long Island Sound. Consequently, a seemingly homogeneous group of fish tagged at the same time in the same non-natal feeding location exhibited a diversity of southward movement patterns that could affect population-level processes. These three groups that differed in overwintering location and migration route could be movement contingents with migratory connectivity.

Acute mastoiditis in children: contemporary opportunities and challenges.

BACKGROUND: Mastoiditis is the most common intra-temporal complication of acute otitis media. Despite potentially lethal sequelae, optimal management remains poorly defined. METHOD: A retrospective case review was conducted of children diagnosed with mastoiditis at a tertiary referral centre, in North East England, between 2010 and 2017. RESULTS: Fifty-one cases were identified, 49 without cholesteatoma. Median patient age was 42 months (2 months to 18 years) and median hospital stay was 4 days (range, 0-27 days). There was no incidence trend over time. Imaging was conducted in 15 out of 49 cases. Surgery was performed in 29 out of 49 cases, most commonly mastoidectomy with (9 out of 29) or without (9 out of 29) grommets. Complications included sigmoid sinus thrombosis (3 out of 49) and extradural abscess (2 out of 51), amongst others; no fatalities occurred. CONCLUSION: A detailed contemporary description of paediatric mastoiditis presentation and management is presented. The findings broadly mirror those published by other UK centres, but suggest a higher rate of identified disease complications and surgical interventions.

A Sheep in Wolf's Clothing: Tephritid Flies Mimic Spider Predators.

Mimicry where prey resemble predators to avoid predation is unusual. Snowberry flies, Rhagoletis zephyria Snow, possess striped wing patterns that resemble the legs of jumping spiders. Observations and comparisons of responses of the jumping spider Salticus scenicus (Clerck) to conspecifics, snowberry flies, and other prey flies showed that snowberry flies can avoid predation by jumping spiders through spider mimicry. The mimicry effect was decreased by obliterating snowberry fly wing stripes.

Radiology of acute mastoiditis and its complications: a pictorial review and interpretation checklist.

BACKGROUND: Mastoiditis is an otological emergency, and cross-sectional imaging has a role in the diagnosis of complications and surgical planning. Advances in imaging technology are becoming increasingly sophisticated and, by the same token, the ability to accurately interpret findings is essential. METHODS: This paper reviews common and rare complications of mastoiditis using case-led examples. A radiologist-derived systematic checklist is proposed, to assist the ENT surgeon with interpreting cross-sectional imaging in emergency mastoiditis cases when the opinion of a head and neck radiologist may be difficult to obtain. RESULTS: A 16-point checklist (the 'mastoid 16') was used on a case-led basis to review the radiological features of both common and rare complications of mastoiditis; this is complemented with imaging examples. CONCLUSION: Acute mastoiditis has a range of serious complications that may be amenable to treatment, once diagnosed using appropriate imaging. The proposed checklist provides a systematic approach to identifying complications of mastoiditis.

Medically assisted hydration for palliative care patients.

BACKGROUND: Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the aim of prolonging the length of life of a patient, improving their quality of life, or both. OBJECTIVES: To determine the effect of medically assisted hydration in palliative care patients on their quality and length of life. SEARCH STRATEGY: Studies were identified from searching CENTRAL, MEDLINE (1966 to 2008), EMBASE (1980 to 2008), CINAHL, CANCERLIT, Caresearch, Dissertation abstracts, SCIENCE CITATION INDEX and the reference lists of all eligible studies, key textbooks, and previous systematic reviews. The date of the latest search was February 2008. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) or prospective controlled studies of medically assisted hydration in palliative care patients. DATA COLLECTION AND ANALYSIS: Five relevant studies were identified. These included two RCTs (93 participants), and three prospective controlled trials (360 participants). These were assessed independently by two review authors for quality and validity. The small number of studies and the heterogeneity of the data meant that a quantitative analysis was not possible, so a description of the main findings was included only. MAIN RESULTS: One study found that sedation and myoclonus (involuntary contractions of muscles) were improved more in the intervention group (28 - hydration, 23 - placebo). Another study found that dehydration was significantly higher in the non-hydration group, but that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group (59 - hydration group, 167 - non -hydration group). The other three studies did not show significant differences in outcomes between the two groups. AUTHORS' CONCLUSIONS: There are insufficient good quality studies to make any recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

A post-genomic view of the mitochondrion in malaria parasites.

Mitochondria in Plasmodium parasites have many characteristics that distinguish them from mammalian mitochondria. Selective targeting of malaria parasite mitochondrial physiology has been exploited in successful antimalarial chemotherapy. At present, our understanding of the functions served by the parasite mitochondrion is somewhat limited, but the availability of the genomic sequences makes it possible to develop a framework of possible mitochondrial functions by providing information on genes encoding mitochondrially targeted proteins. This review aims to provide an overview of mitochondrial physiology in this post-genomic era. Although in many cases direct experimental proof for their mitochondrial functions may not be available at present, descriptions of these potential mitochondrial proteins can provide a basis for experimental approaches.

Clinical effectiveness and soft tissue compatibility of a temporary restorative material.

OBJECTIVE: The purpose of this six-week study was to evaluate in vivo the effectiveness of Systemp.inlay as a temporary restorative material. METHOD: Subjects with the proper indication for a class II restoration were entered into the study. Twenty-three subjects and twenty-nine temporary restorations were evaluated at time of placement, three and six weeks. Two faculty members were calibrated to evaluate the material. Following the six-week trial, the temporary restorative material was removed and the test teeth were restored with a definitive restorative material. RESULTS: The temporary restorative material provided mechanical and anticariogenic protection of tooth structure while preventing dental sensitivity and patient discomfort. It promoted soft tissue health as evidenced by the enhanced plaque and gingival indices found associated with the temporarily restored teeth. Its ease of placement and removal makes it an attractive alternative for the dental practitioner. The change in color of the material over the six-week duration of the study may limit its use to posterior teeth and to lingual/palatal surfaces of anterior teeth. CONCLUSION: Ease of placement and removal and retention of the temporary restorative material were extremely good. Marginal and surface integrity of the material was maintained and no or minimal sensitivity was reported throughout the study. The material did not promote the accumulation of plaque nor result in gingival inflammation. The color change noted was not of clinical importance. Therefore, this temporary restorative material was demonstrated to be clinically effective in Class II cavity preparations.

Polycations induce the release of soluble intermembrane mitochondrial proteins.

The release of proapoptotic proteins from the intermembrane space of mitochondria is an early critical step in many pathways to apoptosis. Induction of the mitochondrial permeability transition pore (PTP) was suggested to be the mechanism of the release of soluble mitochondrial intermembrane proteins (SIMP) in apoptosis. However, several studies suggested that proapoptotic proteins (e.g. Bax and Bid) can induce the release of SIMP (e.g. cytochrome c (cyt c) and adenylate kinase 2 (AK2)) in vivo and in vitro independent of PTP. We have found that a number of structurally diverse polycations, such as aliphatic polyamines (e.g. spermine and to a lesser extent spermidine), aminoglycosides (e.g. streptomycin, gentamicin and neomycin), and cytotoxic peptides (e.g. melittin), induce the release of SIMP from liver mitochondria, in vitro. All the polycations released AK2 together with cyt c, suggesting that rupture of the outer membrane is a common mechanism of cyt c release by these polycations. Several polycations (e.g. spermine, spermidine and neomycin) induced SIMP release without inducing significant swelling, and this release was not inhibited significantly by the PTP inhibitor cyclosporin. In contrast, under the same conditions, streptomycin and melittin induced swelling and SIMP release that was inhibited strongly by cyclosporin. Gentamicin-induced swelling and release of SIMP were partially inhibited by cyclosporin. The affinity of polyamines to the anionic phospholipids of the mitochondrial membranes (spermine=neomycin>gentamicin>streptomycin=spermidine) correlated roughly with their ability to induce PTP-independent release of SIMP, which suggests that the binding of polycations to the anionic phospholipids of the outer mitochondrial membrane facilitates the rupture of this membrane. However, some polycations facilitated the induction of PTP, possibly by binding to cardiolipin on the inner membrane. This dual mechanism may be relevant to the induction of SIMP release in apoptosis.

Molecular modeling studies on the proposed NaCl-induced dimerization of Chromatium vinosum high-potential iron protein.

Previous work (Dunham, W.R., Hagen, W.R., Fee, J.A., Sands, R.H., Dunbar, J.B., Humblet, C. (1991) An investigation of Chromatium vinosum high-potential iron-sulfur protein by EPR and Mössbauer spectroscopy; evidence for a freezing-induced dimerization in NaCl solutions, Biochimica Biophysica Acta 1079, 253-262) suggested that under specific solution conditions and slow freezing times, samples of oxidized Chromatium vinosum (Cv) high-potential, iron-sulfur protein (HiPIP) form dimeric structures that exhibit characteristic spin-spin interaction in the EPR spectrum. In that study, it was also shown that two HiPIP molecules could approach each other along their Fe1-S4 axes to a distance of approximately 13-14 A, as required by an analysis of the spin-spin physics. This is made possible because of a flattened surface on one side of the molecule within which S4 may, depending on side-chain motions, interact with solvent (Carter, C.W., Jr., Kraut, J., Freer, S.T., Alden, R.A., Sieker, L.C., Adman, E.T., Jensen, L.H. (1972) A comparison of Fe4S4 clusters in high potential iron protein and in ferredoxin, Proc. Natl. Acad. Sci. USA 69, 3527-3529). Here we describe a computer generated, hypothetical model of this proposed dimeric structure which suggests an energetically favorable interaction between two Cv HiPIP molecules and could account for the experimental observations. Two Cv HiPIP molecules brought together along their Fe1-S4 axes and maintained at a center-to-center distance of 14 A can be rotated with respect to each other so as to create complementary interactions between two glutamine residues, two phenylalanine residues, and two leucine residues, and an energetically unfavorable interaction between two arginine residues. Energy minimization calculations using the program XPLOR indicate that this arrangement may provide an overall energetically favorable interaction between the two HiPIP molecules that is strengthened by site-specific binding of Na and Cl ions.

Conformational studies of Escherichia coli pyruvate oxidase.

Pyruvate oxidase (pyruvate:oxygen oxidoreductase (phosphorylating), EC 1.2.3.3) is a peripheral membrane enzyme from Escherichia coli which utilizes the cofactors thiamin pyrophosphate (TPP) and flavin-adenine dinucleotide (FAD) to catalyze the decarboxylation of pyruvate to acetic acid and carbon dioxide. The specific activity of the oxidase is enhanced 25-fold when assayed in the presence of certain lipids and detergents. Previous studies have demonstrated that the affinity of pyruvate oxidase for phospholipids and detergents is substantially increased when the flavin is reduced. In this paper, several techniques are utilized to probe both the nature of the active site and the conformational changes in the protein which are concomitant with flavin reduction and with the binding of lipids to the enzyme. Analysis of the circular dichroism spectrum in the far ultraviolet region indicates that neither the binding of lipid activators to the oxidase nor reduction of the enzyme-bound flavin by pyruvate has a significant effect on the average secondary structure of the enzyme. High-resolution electron microscopy demonstrates that at low enzyme concentrations, i.e., assay conditions, incubation of the reduced flavoprotein in the presence of an amphiphilic activator does not alter the quaternary structure of pyruvate oxidase. The results indicate that the conformational changes in the protein due either to reduction of the flavin or to the binding of lipid activators are localized.

Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.

The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.

An enhanced broad-host-range vector for gram-negative bacteria: avoiding tetracycline phototoxicity during the growth of photosynthetic bacteria.

A mobilizable, broad-host-range (bhr) plasmid was derived from the widely used IncP1 vector pRK415. The new vector, pRKD418, contains an additional resistance gene and an enlarged multiple cloning site (MCS) region. The optimal growth of pRK415-containing bacteria under photosynthetic conditions generally requires the use of optical filters to protect the selective antibiotic tetracycline (Tc) from photooxidation with the resulting production of toxic photoproducts; pRK415 is not stably maintained in the absence of selective pressure. The addition of a trimethoprim-resistant dihydrofolate reductase-encoding gene provided for optimal photosynthetic growth in the presence of a selective antibiotic without any special apparatus. The presence of an antibiotic marker not found in commonly used cloning vectors in many cases facilitates the subcloning of inserts into the bhr plasmid. The new MCS region provides further cloning flexibility with at least sixteen available restriction sites. Easily constructed derivative plasmids, exemplified by pRKD418KmE, provide a convenient screening procedure for the detection of recombinants during subcloning.

Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial diseases MELAS and LHON.

Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Poracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e ratio and lower deltapsi), but had similar CO activity. These results indicate that both substitutions (F263L > A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.

Unconscious influences on amnesics' word-stem completion.

Amnesic patients and control subjects were asked to complete three-letter word-stems under one of three retrieval conditions. In a direct condition, they were told to use the stems as retrieval cues for words that had just been presented in a study list. In an indirect condition, they were told to use the first word that came to mind with no reference made to the study list. Finally, in an oppositional condition, they were told to use the first word that came to mind unless it had appeared on the study list. During the study list presentation, the patients and controls had analyzed each word according to either semantic (associating to each word) or graphemic (counting letters with enclosed spaces) instructions. The results revealed that the control subjects produced a different number of study words during retrieval as a function of retrieval instructions and encoding condition. The amnesics, however, did not vary their performance as a function of retrieval instructions. Under all conditions, they completed the word-stems far more frequently with words from the study list than would be expected by chance and they consistently produced more semantic than graphemic responses. We concluded that semantic analysis might affect the fluency with which an item occurs for the amnesic, but that the item itself remains independent of the source of that fluency for these patients. Thus, the level of analysis performed on a word during study can affect the unconscious performance of amnesic patients but is unavailable for use during conscious retrieval.