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1.
Nature ; 614(7946): 102-107, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36697827

RESUMEN

Living amphibians (Lissamphibia) include frogs and salamanders (Batrachia) and the limbless worm-like caecilians (Gymnophiona). The estimated Palaeozoic era gymnophionan-batrachian molecular divergence1 suggests a major gap in the record of crown lissamphibians prior to their earliest fossil occurrences in the Triassic period2-6. Recent studies find a monophyletic Batrachia within dissorophoid temnospondyls7-10, but the absence of pre-Jurassic period caecilian fossils11,12 has made their relationships to batrachians and affinities to Palaeozoic tetrapods controversial1,8,13,14. Here we report the geologically oldest stem caecilian-a crown lissamphibian from the Late Triassic epoch of Arizona, USA-extending the caecilian record by around 35 million years. These fossils illuminate the tempo and mode of early caecilian morphological and functional evolution, demonstrating a delayed acquisition of musculoskeletal features associated with fossoriality in living caecilians, including the dual jaw closure mechanism15,16, reduced orbits17 and the tentacular organ18. The provenance of these fossils suggests a Pangaean equatorial origin for caecilians, implying that living caecilian biogeography reflects conserved aspects of caecilian function and physiology19, in combination with vicariance patterns driven by plate tectonics20. These fossils reveal a combination of features that is unique to caecilians alongside features that are shared with batrachian and dissorophoid temnospondyls, providing new and compelling evidence supporting a single origin of living amphibians within dissorophoid temnospondyls.


Asunto(s)
Anfibios , Anuros , Fósiles , Filogenia , Urodelos , Animales , Anfibios/anatomía & histología , Anuros/anatomía & histología , Arizona , Urodelos/anatomía & histología , Órbita/anatomía & histología , Maxilares/anatomía & histología , Sistema Musculoesquelético/anatomía & histología
2.
PLoS Med ; 21(4): e1004296, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38573882

RESUMEN

BACKGROUND: Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral. METHODS AND FINDINGS: A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups. CONCLUSIONS: The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Pérdida Auditiva Sensorineural/cirugía , Pérdida Auditiva/cirugía , Escolaridad
3.
Mol Phylogenet Evol ; 193: 108010, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38195011

RESUMEN

Nidulariaceae, also known as bird's nest fungi, is an understudied group of mushroom-forming fungi. The common name is derived from their nest-like morphology. Bird's nest fungi are ubiquitous wood decomposers or saprobes on dung. Recent studies showed that species in the Nidulariaceae form a monophyletic group with five sub-clades. However, phylogenetic relationships among genera and placement of Nidulariaceae are still unclear. We present phylogenomic analyses of bird's nest fungi and related Agaricales fungi to gain insight into the evolution of Nidulariaceae. A species tree with 17 newly generated genomes of bird's nest fungi and representatives from all major clades of Agaricales was constructed using 1044 single-copy genes to explore the intergeneric relationships and pinpoint the placement of Nidulariaceae within Agaricales. We corroborated the hypothesis that bird's nest fungi are sister to Squamanitaceae, which includes mushroom-shaped fungi with a stipe and pileus that are saprobes and mycoparasites. Lastly, stochastic character mapping of discrete traits on phylogenies (SIMMAP) suggests that the ancestor of bird's nest fungi likely possessed an evanescent, globose peridium without strings attaching to the spore packets (funiculi). This analysis suggests that the funiculus was gained twice and that the persistent, cupulate peridium form was gained at least four times and lost once. However, alternative coding schemes and datasets with a wider array of Agaricales produced conflicting results during ancestral state reconstruction, indicating that there is some uncertainty in the number of peridium transitions and that taxon sampling may significantly alter ancestral state reconstructions. Overall, our results suggest that several key morphological characters of Nidulariaceae have been subject to homoplasy.


Asunto(s)
Cyathus , Animales , Filogenia , Aves
4.
New Phytol ; 238(5): 1849-1864, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36808625

RESUMEN

Forest fungal communities are shaped by the interactions between host tree root systems and the associated soil conditions. We investigated how the soil environment, root morphological traits, and root chemistry influence root-inhabiting fungal communities in three tropical forest sites of varying successional status in Xishuangbanna, China. For 150 trees of 66 species, we measured root morphology and tissue chemistry. Tree species identity was confirmed by sequencing rbcL, and root-associated fungal (RAF) communities were determined using high-throughput ITS2 sequencing. Using distance-based redundancy analysis and hierarchical variation partitioning, we quantified the relative importance of two soil variables (site average total phosphorus and available phosphorus), four root traits (dry matter content, tissue density, specific tip abundance, and forks), and three root tissue elemental concentrations (nitrogen, calcium, and manganese) on RAF community dissimilarity. The root and soil environment collectively explained 23% of RAF compositional variation. Soil phosphorus explained 76% of that variation. Twenty fungal taxa differentiated RAF communities among the three sites. Soil phosphorus most strongly affects RAF assemblages in this tropical forest. Variation in root calcium and manganese concentrations and root morphology among tree hosts, principally an architectural trade-off between dense, highly branched vs less-dense, herringbone-type root systems, are important secondary determinants.


Asunto(s)
Micobioma , Suelo , Calcio , Bosques , Manganeso , Fósforo , Suelo/química , Microbiología del Suelo , Árboles/microbiología
5.
Mycorrhiza ; 33(4): 221-228, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37330423

RESUMEN

Tuber brumale is a European edible truffle species that is often viewed as a contaminant in truffle orchards, as it visually resembles more valuable black truffles such as T. melanosporum, but differs in aroma and flavor and sells for a much lower price. Although T. brumale is not native to or intentionally cultivated in North America, it was reported to have been accidently introduced into British Columbia in 2014 and North Carolina in 2020. However, in winter of 2021, various truffle orchards in eastern North America produced truffles that differed from the anticipated harvest of T. melanosporum. Molecular analysis of these specimens confirmed T. brumale truffle fruiting bodies from ten orchards distributed across six eastern USA states. Phylogenetic analysis of nuclear ribosomal ITS and 28S DNA sequences indicated that all samples belong to the T. brumale A1 haplogroup, the genetic subgroup of T. brumale that is more common in western Europe. This pattern of widespread fruiting of T. brumale in North American truffle orchards is likely the result of T. brumale being introduced in the initial inoculation of trees used as hosts in T. melanosporum truffle cultivation. We review other examples of introduced non-target truffle species and strategies for limiting their impact on truffle cultivation.


Asunto(s)
Micorrizas , Secuencia de Bases , Europa (Continente) , Especies Introducidas , Filogenia
6.
Clin Otolaryngol ; 48(6): 841-862, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37550850

RESUMEN

BACKGROUND: Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics. This systematic review and meta-analysis of randomised controlled trials aims to assess the effectiveness of topical non-antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa. METHODS: Systematic review and meta-analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non-antibiotic agents in adults and children with acute otitis externa. Non-antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non-pharmaceuticals and astringents. RESULTS: Seventeen trials were eligible for inclusion, with 10 combined in meta-analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta-analysis. CONCLUSION: Antiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.


Asunto(s)
Antiinfecciosos Locales , Otitis Externa , Adulto , Niño , Humanos , Antibacterianos/uso terapéutico , Otitis Externa/tratamiento farmacológico , Antiinfecciosos Locales/uso terapéutico , Inflamación , Enfermedad Aguda , Esteroides
7.
Clin Otolaryngol ; 48(5): 740-747, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37183531

RESUMEN

OBJECTIVES: Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE. DESIGN: Retrospective observational analysis. SETTING: Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity. PARTICIPANTS: Individual aural swabs from 7200 patients. MAIN OUTCOME MEASURES: Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05). RESULTS: From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p = 0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01). CONCLUSION: Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.


Asunto(s)
Otitis Externa , Otitis Media , Adulto , Niño , Humanos , Otitis Externa/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Otitis Media/tratamiento farmacológico , Haemophilus influenzae
8.
Clin Otolaryngol ; 48(4): 638-647, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37051731

RESUMEN

OBJECTIVES: To estimate the prevalence of, and risk factors associated with electrode migration (EM) in cochlear implant (CI) recipients. DESIGN: Historical cohort study of all CIs performed between 1 January 2018 and 1 August 2021 in a single tertiary adult and paediatric CI centre in the UK. MAIN OUTCOME MEASURES: The primary aim is to determine the prevalence of electrode migration, comparing intraoperative surgeon report and examination of a routine plain radiograph performed 2 weeks after surgery. EM is defined as the detection of movement of two or more electrodes out of the cochlea from the time of surgery. Multivariate analysis was performed to investigate preoperative and intraoperative risk factors that might predispose to migration. RESULTS: Four hundred and sixty-five patients, having 516 distinct surgeries, with 628 implants were analysed. EM occurred following 11.5% of implant operations. Pre-existing cochlear abnormality was an independent associated risk factor for EM (OR: 3.40 ⟨1.20-9.62⟩ p = .021). Demographics, surgical technique, usage of a precurved electrode, CSF leak, surgeon seniority and intraoperative telemetry did not influence risk of migration. There were 5 implants (0.8%) which migrated later than 2 weeks, with a median date of imaging diagnosis (x-ray or CT scan) of 263 days ⟨IQR:198⟩, for which head injury was a common precipitating factor. There were differences in the risk of migration between different lateral wall electrodes. CONCLUSION: EM in the early postoperative period is a common occurrence and is more likely in implant recipients with obstructed or malformed cochleae.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Niño , Adulto , Humanos , Implantación Coclear/métodos , Estudios de Cohortes , Electrodos Implantados , Estudios Retrospectivos , Implantes Cocleares/efectos adversos , Periodo Posoperatorio
9.
Mycorrhiza ; 32(5-6): 465-480, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36210381

RESUMEN

The south Florida pine rocklands is a critically endangered, fire-dependent ecosystem dominated by the overstory tree Pinus densa (South Florida slash pine). Because pine recruitment in this ecosystem has proven problematic, restoration efforts need to include replanting slash pine trees. Even though ectomycorrhizal fungi are known to be critical symbionts of young pines and are necessary for the development of healthy pines, virtually nothing is known about these mutualists and their role in pine establishment and survival in the pine rocklands. One approach to improve pine establishment is to grow seedlings in a nursery before outplanting, facilitating early associations with ectomycorrhizae, and therefore improving seedling health. In this study, we compared health metrics (height, stem diameter, final needle length, root length, root colonization, needle greenness, root volume, and root:shoot ratio) of seedlings grown in soil amended with five commercially available mycorrhizal inocula versus field soil collected from three pine rockland fragments. Seedlings grown with native field soil from the pine rocklands generally performed better than those grown with commercial inoculum in all metrics except root length. According to their labels, each commercial inoculum contained between 4 and 10 ectomycorrhizal fungi species. However, no ectomycorrhizal fungi were recovered from two of the inoculum products and only three ectomycorrhizal fungi in total were recovered from the other three products. In contrast, seedlings grown with field soil are associated with ten ectomycorrhizal species. Our results highlight the importance of incorporating native ectomycorrhizal fungi into pine seedling replanting as part of restoration efforts in the pine rocklands.


Asunto(s)
Micorrizas , Pinus , Ecosistema , Pinus/microbiología , Plantones/microbiología , Suelo
10.
Clin Otolaryngol ; 47(1): 120-130, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34606691

RESUMEN

OBJECTIVES: To explore the impact of COVID-19 on the management and outcomes of acute paediatric mastoiditis across the UK. DESIGN: National retrospective and prospective audit. SETTING: 48 UK secondary care ENT departments. PARTICIPANTS: Consecutive children aged 18 years or under, referred to ENT with a clinical diagnosis of mastoiditis. MAIN OUTCOME MEASURES: Cases were divided into Period 1 (01/11/19-15/03/20), before the UK population were instructed to reduce social contact, and Period 2 (16/03/20-30/04/21), following this. Periods 1 and 2 were compared for population variables, management and outcomes. Secondary analyses compared outcomes by primary treatment (medical/needle aspiration/surgical). RESULTS: 286 cases met criteria (median 4 per site, range 0-24). 9.4 cases were recorded per week in period 1 versus 2.0 in period 2, with no winter increase in cases in December 2020-Febraury 2021. Patient age differed between periods 1 and 2 (3.2 vs 4.7 years respectively, p < 0.001). 85% of children in period 2 were tested for COVID-19 with a single positive test. In period, 2 cases associated with P. aeruginosa significantly increased. 48.6% of children were scanned in period 1 vs 41.1% in period 2. Surgical management was used more frequently in period 1 (43.0% vs 24.3%, p = 0.001). Treatment success was high, with failure of initial management in 6.3%, and 30-day re-admission for recurrence in 2.1%. The adverse event rate (15.7% overall) did not vary by treatment modality or between periods 1& 2. CONCLUSION: The COVID-19 pandemic led to a significant change in the presentation and case mix of acute paediatric mastoiditis in the UK.


Asunto(s)
COVID-19/epidemiología , Mastoiditis/epidemiología , Enfermedad Aguda , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Pandemias , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , Estaciones del Año , Reino Unido/epidemiología
11.
Clin Otolaryngol ; 46(3): 485-493, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33453137

RESUMEN

INTRODUCTION: Nasal packing is the mainstay of epistaxis management; however, packs cause patient discomfort and can lead to hospital admission. Absorbable haemostats provide clotting factors or act as a substrate to stimulate clotting and represent a potential treatment alternative. A systematic review was performed to evaluate the efficacy of topical haemostats in the management of epistaxis. METHODS: A systematic literature search of 7 databases was performed. Only eligible randomised controlled trials (RCTs) and observational studies were included. The primary outcome was short-term haemostatic success (<7 days). Secondary outcomes included long-term haemostatic control (no rebleeding 7-30 days), patient discomfort and adverse effects. Meta-analysis was performed where possible. RESULTS: Of 2249 records identified, 12 were included in the qualitative synthesis and 4 RCTs were included in meta-analysis. The following haemostats were reported: gelatin-thrombin matrix (n = 8), aerosolised/gel tranexamic acid (n = 1), cellulose agents (n = 2) and fibrin sealants (n = 1). Studies involving tranexamic acid on removable delivery devices (eg, pledgets) were excluded. There was heterogeneity in outcome measures and inclusion criteria (coagulopathies/anticoagulants were excluded in 3 RCTs and 2 observational studies). The short-term haemostatic success varied between studies (13.9% to 100%). No significant post-procedural complications were reported. The meta-analysis favoured absorbable haemostatic agent versus packing (risk ratio 1.20; 95% confidence interval 1.05 to 1.37; P = .007). The risk of bias across all studies was moderate to high. CONCLUSIONS: The evidence suggests haemostatic agents are effective at managing acute epistaxis when compared with nasal packing. More data are required before recommendations can be made regarding management in patients on anticoagulants.


Asunto(s)
Epistaxis/tratamiento farmacológico , Hemostáticos/administración & dosificación , Administración Intranasal , Administración Tópica , Humanos
12.
Clin Otolaryngol ; 46(3): 552-561, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33377276

RESUMEN

OBJECTIVES: To assess the safety of paediatric tonsillectomy procedures conducted in NHS hospitals in England between 2008 and 2019. DESIGN: Retrospective observational cohort study using Hospital Episode Statistics (HES) data. SETTING: Acute NHS trusts in England conducting paediatric tonsillectomy procedures. PARTICIPANTS: Children (≤16 years old) undergoing bilateral tonsillectomy. MAIN OUTCOME MEASURES: Number of tonsillectomies performed per year by procedural method. In-hospital complications including return to theatre for arrest of haemorrhage. Readmission within 28 days, including those for pain, haemorrhage and surgical arrest of haemorrhage. Long-term outcomes: all-cause mortality, revision tonsillectomy. RESULTS: A total of 318 453 paediatric tonsillectomies were performed from 2008 to 2019:278,772 dissection (87.5%) and 39 681 coblation (12.5%). The proportion of tonsillectomy performed using coblation increased from 7% in 2008/9 to 27% in 2018/9. Five patients died in hospital (including 4 due to respiratory complications). In-hospital complications occurred in 4202 children (1.3%), with the most frequent being haemorrhage. Within 28 days of tonsillectomy, 28 170 patients (8.8%) were readmitted and 7 deaths occurred. Readmission rates for haemorrhage and pain have increased since 2008. The proportion of children undergoing revision tonsillectomy procedures within 5 years following coblation tonsillectomy (1.4%) was approximately double that of dissection (0.6%). CONCLUSIONS: Clinical practice of paediatric tonsillectomy has changed in England over the past 11 years. The overall mortality rate associated with the procedure is 0.0037%. Differences in outcomes have been identified for different procedural methods. However, routine administrative data are limited in differentiating procedural detail (eg we are unable to differentiate intra or extra-capsular techniques from current clinical coding of tonsillectomy procedures). Therefore, prospective national data collection or more granular clinical coding is essential to capture relative outcomes of the different tonsillectomy methods and techniques being used in the NHS.


Asunto(s)
Evaluación de Resultado en la Atención de Salud , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tonsilectomía/estadística & datos numéricos , Adolescente , Niño , Preescolar , Inglaterra , Femenino , Humanos , Lactante , Masculino , Complicaciones Posoperatorias , Estudios Retrospectivos
13.
Metab Eng ; 59: 98-105, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32061967

RESUMEN

There is a desire to engineer mammalian host cell lines to improve cell growth/biomass accumulation and recombinant biopharmaceutical protein production in industrially relevant cell lines such as the CHOK1 and HEK293 cell lines. The over-expression of individual subunits of the eukaryotic translation factor eIF3 in mammalian cells has previously been shown to result in oncogenic properties being imparted on cells, including increased cell proliferation and growth and enhanced global protein synthesis rates. Here we report on the engineering of CHOK1 and HEK cells to over-express the eIF3i and eIF3c subunits of the eIF3 complex and the resultant impact on cell growth and a reporter of exogenous recombinant protein production. Transient over-expression of eIF3i in HEK293 and CHOK1 cells resulted in a modest increase in total eIF3i amounts (maximum 40% increase above control) and an approximate 10% increase in global protein synthesis rates in CHOK1 cells. Stable over-expression of eIF3i in CHOK1 cells was not achievable, most likely due to the already high levels of eIF3i in CHO cells compared to HEK293 cells, but was achieved in HEK293 cells. HEK293 cells engineered to over-express eIF3i had faster growth that was associated with increased c-Myc expression, achieved higher cell biomass and gave enhanced yields of a reporter of recombinant protein production. Whilst CHOK1 cells could not be engineered to over-express eIF3i directly, they could be engineered to over-express eIF3c, which resulted in a subsequent increase in eIF3i amounts and c-Myc expression. The CHOK1 eIF3c engineered cells grew to higher cell numbers and had enhanced cap- and IRES-dependent recombinant protein synthesis. Collectively these data show that engineering of subunits of the eIF3 complex can enhance cell growth and recombinant protein synthesis in mammalian cells in a cell specific manner that has implications for the engineering or selection of fast growing or high producing cells for production of recombinant proteins.


Asunto(s)
Factor 3 de Iniciación Eucariótica , Regulación de la Expresión Génica , Proteínas Proto-Oncogénicas c-myc , Animales , Células CHO , Cricetulus , Factor 3 de Iniciación Eucariótica/biosíntesis , Factor 3 de Iniciación Eucariótica/genética , Células HEK293 , Humanos , Ratones , Células 3T3 NIH , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética
14.
Audiol Neurootol ; 25(5): 249-257, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32454509

RESUMEN

OBJECTIVES: To explore the relationship between aural symptoms during baro-challenge and the underlying measured Eustachian tube (ET) function. Two key questions were addressed. (1) In patients who have features of obstructive ET dysfunction, is there a measurable underlying difference in ET function between those who experience severe symptoms on baro-challenge and those that do not? (2) What is the diagnostic value of ET function tests in the identification of patients with severe symptoms on baro-challenge? METHODS: Patients with symptoms of obstructive ET dysfunction were recruited, with the presence of aural symptoms on baro-challenge established via the clinical history and analysis of the Cambridge ET Dysfunction Assessment, a patient-reported outcome measure (PROM). ET function tests were assessed in each patient: 9 objective and semi-objective measures of ET opening, and 2 symptom-based PROMs. The tests' results were grouped by type of ET opening assessed, generating passive and active dysfunction scores. Individual test results were assessed for diagnostic accuracy in reference to features in the history or PROM-based evidence of symptoms on baro-challenge. RESULTS: Both passive and active opening of the ET was significantly reduced in ears with a history of pain on baro-challenge. Some patients had apparent severe obstructive ET dysfunction without symptoms on baro-challenge, whilst others had symptoms but normal test results. No individual test of ET opening was of diagnostic value in predicting those ears likely to experience pain or exacerbated symptoms on baro-challenge. CONCLUSION: The relationship between aural pain during baro-challenge and ET function appears more complex than had been assumed, with pain possibly related to factors other than just ET function.


Asunto(s)
Enfermedades del Oído/fisiopatología , Trompa Auditiva/fisiopatología , Presión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Examen Físico , Adulto Joven
16.
Plant Dis ; 104(12): 3143-3150, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33136520

RESUMEN

Ambrosia beetles in the subtribe Hyorrhynchini are one example of an entire ambrosia beetle lineage whose fungi have never been studied. Here, we identify one dominant fungus associated with a widespread Asian hyorrhynchine beetle Sueus niisimai. This fungus was consistently isolated from beetle galleries from multiple collections. Phylogenetic analyses of combined ITS rDNA and ß-tubulin sequences identified the primary fungal symbiont as Diatrypella japonica Higuchi, Nikaido & Hattori (Diatrypaceae, Xylariales, Sordariomycetes), which was recently described as a pathogen of sycamore (Platanus spp.) in Japan. To assess the invasion potential of this beetle-fungus interaction into the U.S., we have investigated the pathogenicity of two D. japonica strains on four species of healthy landscape trees native to the southeastern United States. Only Shumard oak (Quercus shumardii) responded with lesions significantly greater than the control inoculations, but there was no observable dieback or tree mortality. Although disease symptoms were not as prominent as in previous studies of the same fungus in Japan, routine reisolation from the inoculation point suggests that this species is capable of colonizing healthy sapwood of several tree species. Our study shows that the geographical area of its distribution is broader in Asia and potentially includes many hosts of its polyphagous vector. We conclude that the Sueus-Diatrypella symbiosis has high invasion potential but low damage potential, at least on young trees during the growing season.


Asunto(s)
Escarabajos , Enfermedad , Gorgojos , Xylariales , Ambrosia , Animales , Japón , Filogenia , Enfermedades de las Plantas , Sudeste de Estados Unidos
17.
Clin Otolaryngol ; 45(1): 83-98, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31670912

RESUMEN

OBJECTIVES: The roles of Allied Health Care Professionals (AHPs) in Head and Neck Cancer (HNC) are wide ranging but not clearly defined. Inter-regional variability in practice results from a lack of standardisation in approaches to the Multidisciplinary Team (MDT) make-up and structure. Traditionally, the follow-up of HNC patients is clinician led with multiple scheduled follow-up appointments. The increasing population of HNC patients provides logistical, monetary and efficiency challenges. This systematic review presents the roles of the multiple AHP sub-groups in HNC with the aim of presenting how their differing skill sets can be integrated to modernise our approach in follow-up. DESIGN: We searched MEDLINE, Embase, the Cochrane Library, NIHR Dissemination Centre, The Kings Fund Library, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify multiple subgroups of AHPs (Dentists, Speech and Language Therapists, Dieticians, Physiotherapists, Psychologists, Clinical Nurse Specialists) and evidence of their role in HNC follow-up. Evidence not directly relating to HNC follow-up was excluded. SETTING AND PARTICIPANTS: This Systematic Review was undertaken online by the Integrate (UK ENT Trainee National Collaborative) Head and Neck Subcommittee. MAIN OUTCOME MEASURES: Most evidence was of low-quality, and the broad nature of the protocol provided a wide variety of study models. Two authors screened the articles for relevance to the topic before final analysis. RESULTS: The main role identified was improvement in Quality of Life and symptom control rather than detecting recurrence. We also demonstrate that it is possible to stratify HNC follow-up patients using their received treatment modality and Distress Thermometers to identify groups who will require more intensive AHP input. CONCLUSIONS: HNC follow-up covers a broad group of patients with differing needs. As such, a blanket approach to this phase of treatment is likely to be less effective than a patient-led model where the group of AHPs are employed on a needs basis rather than at set time points. This will likely lead to greater patient satisfaction, earlier detection of recurrence and efficiency savings.


Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico , Personal de Salud/normas , Satisfacción del Paciente , Calidad de Vida , Humanos
18.
New Phytol ; 222(4): 1936-1950, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30689219

RESUMEN

The biological and functional diversity of ectomycorrhizal (ECM) associations remain largely unknown in South America. In Patagonia, the ECM tree Nothofagus pumilio forms monospecific forests along mountain slopes without confounding effects of vegetation on plant-fungi interactions. To determine how fungal diversity and function are linked to elevation, we characterized fungal communities, edaphic variables, and eight extracellular enzyme activities along six elevation transects in Tierra del Fuego (Argentina and Chile). We also tested whether pairing ITS1 rDNA Illumina sequences generated taxonomic biases related to sequence length. Fungal community shifts across elevations were mediated primarily by soil pH with the most species-rich fungal families occurring mostly within a narrow pH range. By contrast, enzyme activities were minimally influenced by elevation but correlated with soil factors, especially total soil carbon. The activity of leucine aminopeptidase was positively correlated with ECM fungal richness and abundance, and acid phosphatase was correlated with nonECM fungal abundance. Several fungal lineages were undetected when using exclusively paired or unpaired forward ITS1 sequences, and these taxonomic biases need reconsideration for future studies. Our results suggest that soil fungi in N. pumilio forests are functionally similar across elevations and that these diverse communities help to maintain nutrient mobilization across the elevation gradient.


Asunto(s)
Micorrizas/fisiología , Suelo/química , Secuencia de Bases , Biodiversidad , Chile , ADN Ribosómico/genética , Ambiente , Geografía
19.
New Phytol ; 222(1): 511-525, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30485448

RESUMEN

Endogonales (Mucoromycotina), composed of Endogonaceae and Densosporaceae, is the only known non-Dikarya order with ectomycorrhizal members. They also form mycorrhizal-like association with some nonspermatophyte plants. It has been recently proposed that Endogonales were among the earliest mycorrhizal partners with land plants. It remains unknown whether Endogonales possess genomes with mycorrhizal-lifestyle signatures and whether Endogonales originated around the same time as land plants did. We sampled sporocarp tissue from four Endogonaceae collections and performed shotgun genome sequencing. After binning the metagenome data, we assembled and annotated the Endogonaceae genomes. We performed comparative analysis on plant-cell-wall-degrading enzymes (PCWDEs) and small secreted proteins (SSPs). We inferred phylogenetic placement of Endogonaceae and estimated the ages of Endogonaceae and Endogonales with expanded taxon sampling. Endogonaceae have large genomes with high repeat content, low diversity of PCWDEs, but without elevated SSP/secretome ratios. Dating analysis estimated that Endogonaceae originated in the Permian-Triassic boundary and Endogonales originated in the mid-late Silurian. Mycoplasma-related endobacterium sequences were identified in three Endogonaceae genomes. Endogonaceae genomes possess typical signatures of mycorrhizal lifestyle. The early origin of Endogonales suggests that the mycorrhizal association between Endogonales and plants might have played an important role during the colonization of land by plants.


Asunto(s)
Evolución Biológica , Mucorales/genética , Micorrizas/fisiología , Filogenia , Genoma Fúngico , Metagenómica , Microbiota/genética , Anotación de Secuencia Molecular , Mycoplasma/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética
20.
Mol Phylogenet Evol ; 133: 152-163, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30639767

RESUMEN

Previous genome-scale phylogenetic analyses of Fungi have under sampled taxa from Zoopagales; this order contains many predacious or parasitic genera, and most have never been grown in pure culture. We sequenced the genomes of 4 zoopagalean taxa that are predators of amoebae, nematodes, or rotifers and the genome of one taxon that is a parasite of amoebae using single cell sequencing methods with whole genome amplification. Each genome was a metagenome, which was assembled and binned using multiple techniques to identify the target genomes. We inferred phylogenies with both super matrix and coalescent approaches using 192 conserved proteins mined from the target genomes and performed ancestral state reconstructions to determine the ancestral trophic lifestyle of the clade. Our results indicate that Zoopagales is monophyletic. Ancestral state reconstructions provide moderate support for mycoparasitism being the ancestral state of the clade.


Asunto(s)
Hongos/clasificación , Hongos/genética , Genoma Fúngico , Filogenia , Animales , Secuencia de Bases , Proteínas Fúngicas/genética , Biblioteca de Genes , Genómica , Funciones de Verosimilitud , Simbiosis/genética
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