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1.
Int J Audiol ; 62(7): 682-687, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35574926

RESUMO

OBJECTIVE: The use of various types of filtering facepiece class 3 (FFP3) mask have become commonplace since the Covid-19 outbreak. These have been evaluated in terms of efficacy regarding aerosol filtration but less emphasis has been placed on the acoustic effects of such masks and their consequences for clinical communication. DESIGN: A microphone 65 cm from a sound-producing Head and Torso Simulator (wearing the masks) was used to measure attenuation via a tone sweep. Predicted impact on speech reception in noise was assessed by weighting the attenuations of cochlear excitation patterns by the frequency importance function of the Speech Intelligibility Index. STUDY SAMPLE: We evaluated acoustic attenuation properties of seven FFP3 masks and a Type IIR surgical mask (as a comparator). RESULTS: The Type IIR mask had the smallest impact on SNR (2.6 dB with visor). Most FFP3s with an addition of a visor (if not already face covering) impacted SNR by approximately 6 dB. The 3 M 6000 was significantly worse (15.8 dB). CONCLUSIONS: Mouth-and-nose covering FFP3s masks had similar effects on SNR (≈6.2 dB with visor). The Tecmen TM-H2 had several advantages over other masks evaluated. It was reusable, allowed lipreading clues and the attenuation was similar to other FFP3s.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , Equipamento de Proteção Individual , Ruído/efeitos adversos , Ruído/prevenção & controle , Inteligibilidade da Fala , Acústica
2.
J Strength Cond Res ; 37(2): 457-481, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36165995

RESUMO

ABSTRACT: Hall, AJ, Aspe, RR, Craig, TP, Kavaliauskas, M, Babraj, J, and Swinton, PA. The effects of sprint interval training on physical performance: a systematic review and meta-analysis. J Strength Cond Res 37(2): 457-481, 2023-The present study aimed to synthesize findings from published research and through meta-analysis quantify the effect of sprint interval training (SIT) and potential moderators on physical performance outcomes (categorized as aerobic, anaerobic, mixed aerobic-anaerobic, or muscular force) with healthy adults, in addition to assessing the methodological quality of included studies and the existence of small study effects. Fifty-five studies were included (50% moderate methodological quality, 42% low methodological quality), with 58% comprising an intervention duration of ≤4 weeks and an array of different training protocols. Bayesian's meta-analysis of standardized mean differences (SMD) identified a medium effect of improved physical performance with SIT (ES 0.5 = 0.52; 95% credible intervals [CrI]: 0.42-0.62). Moderator analyses identified overlap between outcome types with the largest effects estimated for anaerobic outcomes (ES 0.5 = 0.61; 95% CrI: 0.48-0.75). Moderator effects were identified for intervention duration, sprint length, and number of sprints performed per session, with larger effects obtained for greater values of each moderator. A substantive number of very large effect sizes (41 SMDs > 2) were identified with additional evidence of extensive small study effects. This meta-analysis demonstrates that short-term SIT interventions are effective for developing moderate improvements in physical performance outcomes. However, extensive small study effects, likely influenced by researchers analyzing many outcomes, suggest potential overestimation of reported effects. Future research should analyze fewer a priori selected outcomes and investigate models to progress SIT interventions for longer-term performance improvements.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adulto , Humanos , Treinamento Intervalado de Alta Intensidade/métodos , Teorema de Bayes , Força Muscular , Desempenho Físico Funcional
3.
J Sports Sci ; 40(18): 2047-2054, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36184114

RESUMO

The magnitude of change following strength and conditioning (S&C) training can be evaluated comparing effect sizes to thresholds. This study conducted a series of meta-analyses and compiled results to identify thresholds specific to S&C, and create prior distributions for Bayesian updating. Pre- and post-training data from S&C interventions were translated into standardised mean difference (SMDpre) and percentage improvement (%Improve) effect sizes. Bayesian hierarchical meta-analysis models were conducted to compare effect sizes, develop prior distributions, and estimate 0.25-, 0.5-, and 0.75-quantiles to determine small, medium, and large thresholds, respectively. Data from 643 studies comprising 6574 effect sizes were included in the analyses. Large differences in distributions for both SMDpre and %Improve were identified across outcome domains (strength, power, jump and sprint performance), with analyses of the tails of the distributions indicating potential large overestimations of SMDpre values. Future evaluations of S&C training will be improved using Bayesian approaches featuring the information and priors developed in this study. To facilitate an uptake of Bayesian methods within S&C, an easily accessible tool employing intuitive Bayesian updating was created. It is recommended that the tool and specific thresholds be used instead of isolated effect size calculations and Cohen's generic values when evaluating S&C training.


Assuntos
Treinamento Resistido , Humanos , Teorema de Bayes
4.
Int J Mol Sci ; 21(20)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081245

RESUMO

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Proliferação de Células , Sobrevivência Celular , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Regulação para Baixo , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo
6.
Agric Syst ; 165: 344-353, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32287945

RESUMO

Food insecurity persists in many parts of Africa and Asia, despite ongoing agricultural research for development (AR4D) interventions. This is resulting in a growing demand for alternative approaches to designing and evaluating interventions in complex systems. Theory of Change (ToC) is an approach which may be useful because it enables stakeholders to present and test their theories and assumptions about why and how impact may occur, ideally within an environment conducive to iterative reflection and learning. However, ToC is yet to be appropriately mainstreamed into development by donors, researchers and practitioners. We carried out a literature review, triangulated by interviews with 26 experts in African and Asian food security, consisting of researchers, advisors to programs, and donors. Although 17 (65%) of the experts had adopted ToC, their responses and the literature revealed four challenges to mainstreaming: (i) different interpretations of ToC; (ii) incoherence in relationships among the constituent concepts of ToC; (iii) confused relationships between ToC and project "logframes"; and (iv) limitations in necessary skills and commitment for enacting ToC. A case study of the evolution of a ToC in a West African AR4D project over 4 years which exemplified these challenges is presented. Five recommendations arise to assist the mainstreaming of ToC: (i) select a type of ToC suited to the relative complexity of the problem and focal system of interest; (ii) state a theory or hypotheses to be tested as the intervention progresses; (iii) articulate the relationship between the ToC and parallel approaches (e.g. logframe); (iv) accept that a ToC is a process, and (v) allow time and resources for implementers and researchers to develop ToC thinking within projects. Finally, we suggest that communities of practice should be established among AR4D and donor organisations to test, evaluate and improve the contribution that ToCs can make to sustainable food security and agricultural development.

7.
BMC Health Serv Res ; 14: 292, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25001236

RESUMO

BACKGROUND: Parents of children and young people with long-term conditions who need to deliver clinical care to their child at home with remote support from hospital-based professionals, often search the internet for care-giving information. However, there is little evidence that the information available online was developed and evaluated with parents or that it acknowledges the communities of practice that exist as parents and healthcare professionals share responsibility for condition management. METHODS: The data reported here are part of a wider study that developed and tested a condition-specific, online parent information and support application with children and young people with chronic-kidney disease, parents and professionals. Semi-structured interviews were conducted with 19 fathers and 24 mothers who had recently tested the novel application. Data were analysed using Framework Analysis and the Communities of Practice concept. RESULTS: Evolving communities of child-healthcare practice were identified comprising three components and several sub components: (1) Experiencing (parents making sense of clinical tasks) through Normalising care, Normalising illness, Acceptance & action, Gaining strength from the affected child and Building relationships to formalise a routine; (2) Doing (Parents executing tasks according to their individual skills) illustrated by Developing coping strategies, Importance of parents' efficacy of care and Fear of the child's health failing; and (3) Belonging/Becoming (Parents defining task and group members' worth and creating a personal identity within the community) consisting of Information sharing, Negotiation with health professionals and Achieving expertise in care. Parents also recalled factors affecting the development of their respective communities of healthcare practice; these included Service transition, Poor parent social life, Psycho-social affects, Family chronic illness, Difficulty in learning new procedures, Shielding and avoidance, and Language and cultural barriers. Health care professionals will benefit from using the communities of child-healthcare practice model when they support parents of children with chronic kidney disease. CONCLUSIONS: Understanding some of the factors that may influence the development of communities of child-healthcare practice will help professionals to tailor information and support for parents learning to manage their child's healthcare. Our results are potentially transferrable to professionals managing the care of children and young people with other long-term conditions.


Assuntos
Informação de Saúde ao Consumidor , Gerenciamento Clínico , Comportamento de Busca de Informação , Internet , Pais/psicologia , Insuficiência Renal Crônica/enfermagem , Adaptação Psicológica , Adolescente , Criança , Pré-Escolar , Inglaterra , Feminino , Serviços Hospitalares de Assistência Domiciliar , Humanos , Lactente , Masculino , Relações Pais-Filho , Pesquisa Qualitativa , Apoio Social
8.
Genes Chromosomes Cancer ; 51(3): 250-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22072526

RESUMO

Casitas B-lineage lymphoma (CBL) proteins are RING finger ubiquitin E3 ligases that attenuate the signaling of receptor tyrosine kinases and are mutated in a number of myeloid disorders. In this study, mutational screening of the linker-RING domains of CBL and CBLB was performed by denaturing high performance liquid chromatography in a cohort of diagnostic (n = 180) or relapse (n = 46) samples from children with acute lymphoblastic leukemia. Somatic mutations were identified in three children, giving an overall incidence of 1.7% and involved small deletions affecting the intron/exon boundaries of exon 8, leading to skipping of exon 8 and abolishing E3 ligase function. Mutated primary samples were associated with constitutive activation of the RAS pathway and sensitivity to MEK inhibitors was shown. Thus, mutation of CBL is an alternative route to activate the RAS pathway and may identify children who are candidates for MEK inhibitor clinical trials.


Assuntos
Mutação , Proteína Oncogênica v-cbl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transdução de Sinais/genética , Adolescente , Sequência de Bases , Criança , Pré-Escolar , Cromatografia Líquida , Estudos de Coortes , Análise Mutacional de DNA , Éxons , Feminino , Humanos , Íntrons , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Masculino , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Domínios RING Finger , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Recidiva , Reino Unido
9.
Sports Med ; 53(9): 1693-1708, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37493929

RESUMO

BACKGROUND: Load-velocity relationships are commonly used to estimate one-repetition maximums (1RMs). Proponents suggest these estimates can be obtained at high frequencies and assist with manipulating loads according to session-by-session fluctuations. Given their increasing popularity and development of associated technologies, a range of load-velocity approaches have been investigated. OBJECTIVE: This systematic review and individual participant data (IPD) meta-analysis sought to quantify the predictive validity of individualised load-velocity relationships for the purposes of 1RM prediction. METHODS: In September 2022, a search of MEDLINE, SPORTDiscus, Web of Science and Scopus was conducted for published research, with Google Scholar, CORE and British Ethos also searched for unpublished research. Studies were eligible if they were written in English, and directly compared a measured and predicted 1RM using load-velocity relationships in the squat, bench press, deadlift, clean or snatch. IPD were obtained through requests to primary authors and through digitisation of in-text plots (e.g. Bland-Altman plots). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the review conducted in accordance with PRISMA-IPD guidelines and an a priori protocol. Absolute and scaled standard error of the estimates (SEE/SEE%) were calculated for two-stage aggregate analyses, with bootstrapping performed for sampling variances. Estimates were pooled using three-level hierarchical models with robust 95% confidence intervals (CIs). One-stage analyses were conducted with random intercepts to account for systematic differences across studies and prediction residuals calculated in the absolute scale (kg) and as a percentage of the measured 1RM. Moderator analyses were conducted by including a priori defined categorical variables as fixed effects. RESULTS: One hundred and thirty-seven models from 26 studies were included with each identified as having low, unclear or high risk of bias. Twenty studies comprising 434 participants provided sufficient data for meta-analyses, with raw data obtained for 8 (32%) studies. Two-stage analyses identified moderate predictive validity [SEE% 9.8, 95% CI 7.4% to 12.2%, with moderator analyses demonstrating limited differences based on the number of loads (ß2Loads:>2Loads = 0.006, 95% CI - 1.6 to 1.6%) or the use of individual or group data to determine 1RM velocity thresholds (ßGroup:Individualised = - 0.4, 95% CI - 1.9 to 1.0%)]. One-stage analyses identified that predictions tended to be overestimations (4.5, 95% CI 1.5 to 7.4 kg), which expressed as a percentage of measured 1RM was equal to 3.7 (95% CI 0.5 to 6.9% 1RM). Moderator analyses were consistent with those conducted for two-stage analyses. CONCLUSIONS: Load-velocity relationships tend to overestimate 1RMs irrespective of the modelling approach selected. On the basis of the findings from this review, practitioners should incorporate direct assessment of 1RM wherever possible. However, load-velocity relationships may still prove useful for general monitoring purposes (e.g. assessing trends across a training cycle), by providing high-frequency estimates of 1RM when direct assessment may not be logistically feasible. Given limited differences in predictions across popular load-velocity approaches, it is recommended that practitioners opting to incorporate this practice select the modelling approach that best suits their practical requirements. REGISTRATION: https://osf.io/agpfm/ .


Assuntos
Terapia por Exercício , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Viés , Postura , Força Muscular , Levantamento de Peso
10.
Proc Natl Acad Sci U S A ; 105(44): 17050-4, 2008 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-18957548

RESUMO

The search for target genes involved in unbalanced acquired chromosomal abnormalities has been largely unsuccessful, because the breakpoints of these rearrangements are too variable. Here, we use the example of dicentric chromosomes in B cell precursor acute lymphoblastic leukemia to show that, despite this heterogeneity, single genes are targeted through a variety of mechanisms. FISH showed that, although they were heterogeneous, breakpoints on 9p resulted in the partial or complete deletion of PAX5. Molecular copy number counting further delineated the breakpoints and facilitated cloning with long-distance inverse PCR. This approach identified 5 fusion gene partners with PAX5: LOC392027 (7p12.1), SLCO1B3 (12p12), ASXL1 (20q11.1), KIF3B (20q11.21), and C20orf112 (20q11.1). In each predicted fusion protein, the DNA-binding paired domain of PAX5 was present. Using quantitative PCR, we demonstrated that both the deletion and gene fusion events resulted in the same underexpression of PAX5, which extended to the differential expression of the PAX5 target genes, EBF1, ALDH1A1, ATP9A, and FLT3. Further molecular analysis showed deletion and mutation of the homologous PAX5 allele, providing further support for the key role of PAX5. Here, we show that specific gene loci may be the target of heterogeneous translocation breakpoints in human cancer, acting through a variety of mechanisms. This approach indicates an application for the identification of cancer genes in solid tumours, where unbalanced chromosomal rearrangements are particularly prevalent and few genes have been identified. It can be extrapolated that this strategy will reveal that the same mechanisms operate in cancer pathogenesis in general.


Assuntos
Quebra Cromossômica , Genes Neoplásicos , Fator de Transcrição PAX5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Translocação Genética/genética , Alelos , Sequência de Bases , Cromossomos Humanos Par 9/genética , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Modelos Genéticos , Dados de Sequência Molecular , Mutação , Proteínas de Fusão Oncogênica/genética , Fator de Transcrição PAX5/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo
12.
Genes Chromosomes Cancer ; 47(12): 1118-25, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18767146

RESUMO

The ETV6-RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in approximately 25% of children with acute lymphoblastic leukemia (ALL). Studies have shown that the fusion alone is insufficient for the initiation of leukemia; additional genetic changes are required. Genomic profiling identified copy number alterations at high frequencies in these patients. Focal deletions of TBL1XR1 were observed in 15% of cases; 3 patients exhibited deletions distal to the gene. Fluorescence in situ hybridization confirmed these deletions and quantitative RT-PCR showed that the TBL1XR1 gene was significantly under-expressed. TBL1XR1 is a key component of the SMRT and N-CoR compressor complexes, which control hormone-receptor mediated gene expression. Differential expression of the retinoic acid target genes, RARB, CRABP1, and CRABP2, indicated that deletion of TBL1XR1 compromised the function of SMRT/N-CoR in the appropriate control of gene expression. This study identifies deletions of TBL1XR1 as a recurrent abnormality in ETV6-RUNX1 positive ALL. We provide evidence that implicates this deletion in the inappropriate control of gene expression in these patients. The target of the interaction between TBL1XR1 and the signaling pathways described here may be exploited in cancer therapy.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Repressoras/genética , Deleção de Sequência , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 21/genética , Humanos , Modelos Genéticos , Translocação Genética
13.
F1000Res ; 8: 975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448108

RESUMO

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects.


Assuntos
Laboratórios , Patologia , Projetos de Pesquisa , Humanos , Patologia/tendências , Reino Unido
14.
Int J Nurs Stud ; 45(5): 750-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17306272

RESUMO

BACKGROUND: Web-based technologies are increasingly being used to create modes of online learning for nurses but their effect has not been assessed in nurse education. OBJECTIVES: Assess whether participation in face-to-face discussion seminars or online asynchronous discussion groups had different effects on educational attainment in a web-based course. DESIGN: Non-randomised or quasi-experimental design with two groups-students choosing to have face-to-face discussion seminars and students choosing to have online discussions. SETTING: The Core Methods module of a postgraduate research methods course. PARTICIPANTS: All 114 students participating in the first 2 yr during which the course teaching material was delivered online. OUTCOME: Assignment mark for Core Methods course module. METHODS: Background details of the students, their choices of modules and assignment marks were collected as part of the routine course administration. Students' online activities were identified using the student tracking facility within WebCT. Regression models were fitted to explore the association between available explanatory variables and assignment mark. RESULTS: Students choosing online discussions had a higher Core Methods assignment mark (mean 60.8/100) than students choosing face-to-face discussions (54.4); the difference was statistically significant (t=3.13, df=102, p=0.002), although this ignores confounding variables. Among online discussion students, assignment mark was significantly correlated with the numbers of discussion messages read (Kendall's tau(b)=0.22, p=0.050) and posted (Kendall's tau(b)=0.27, p=0.017); among face-to-face discussion students, it was significantly associated with the number of non-discussion hits in WebCT (Kendall's tau(b)=0.19, p=0.036). In regression analysis, choice of discussion method, whether an M.Phil./Ph.D. student, number of non-discussion hits in WebCT, number of online discussion messages read and number posted were associated with assignment mark at the 5% level of significance when taken singly; in combination, only whether an M.Phil./Ph.D. student (p=0.024) and number of non-discussion hits (p=0.045) retained significance. CONCLUSIONS: This study demonstrates that a research methods course can be delivered to postgraduate healthcare students at least as successfully by an entirely online method in which students participate in online discussion as by a blended method in which students accessing web-based teaching material attend face-to-face seminar discussions. Increased online activity was associated with higher assignment marks. The study highlights new opportunities for educational research that arise from the use of virtual learning environments that routinely record the activities of learners and tutors.


Assuntos
Atitude do Pessoal de Saúde , Comunicação , Educação de Pós-Graduação em Enfermagem/organização & administração , Internet/organização & administração , Pesquisa em Enfermagem/educação , Estudantes de Enfermagem/psicologia , Adulto , Análise de Variância , Atitude Frente aos Computadores , Comportamento de Escolha , Instrução por Computador/métodos , Inglaterra , Feminino , Humanos , Relações Interprofissionais , Masculino , Pesquisa em Educação em Enfermagem , Pesquisa Metodológica em Enfermagem , Pesquisa em Enfermagem/métodos , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Análise de Regressão , Método Simples-Cego , Inquéritos e Questionários
15.
Int J Pediatr Otorhinolaryngol ; 115: 175-176, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30368381

RESUMO

There are a wide range of genetic and auto-immune conditions where UV light exposure poses a threat of UV irradiation to the external auditory canal, tympanic membrane and surrounding skin. Preoperative Ultraviolet Light (UV) measurements were taken in the operating theatre with standard operating microscope and an approved UV light meter prior to surgery on a patient with xeroderma pigmentosa. UV light meter readings of UV index 75 were taken at an operating distance of 290mm. Proceeding with otological surgery with a high UV index would result in a significant UV radiation burn. Utilising a Dermagard and a specific UV filter applied to the microscope resulted in acceptable UV light readings. We highlight the potential morbidity of otological surgery in paediatric photosensitive conditions. We also recommend a management plan to avoid damage by UV radiation in photosensitive patients.


Assuntos
Ventilação da Orelha Média/efeitos adversos , Exposição à Radiação/prevenção & controle , Raios Ultravioleta/efeitos adversos , Xeroderma Pigmentoso/cirurgia , Pré-Escolar , Humanos , Masculino , Ventilação da Orelha Média/métodos , Otite Média com Derrame/complicações , Otite Média com Derrame/cirurgia , Exposição à Radiação/efeitos adversos , Xeroderma Pigmentoso/complicações
16.
Cochlear Implants Int ; 19(6): 307-311, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30010498

RESUMO

OBJECTIVE: To examine inter-aural hearing preservation results in children undergoing simultaneous bilateral cochlear implantation (CI). METHODS: Retrospective case review in tertiary referral centre. All children undergoing simultaneous bilateral CI between January 2013 and June 2014 (18 months). Patients eligible for inclusion in the study had pre-operative hearing thresholds of <90 dB at 250 Hz and ≥100 dB at 500 Hz. Patients with anatomical cochlear anomalies or missing data were excluded. Seven patients were included, 1 male, 6 female, mean age of 12 years 11 months at the time of surgery. All patients had simultaneous bilateral cochlear implant surgery, using the same implant and technique. All patients had pre- and post-operative unaided pure tone audiometry. Inter-aural hearing preservation results were compared in each patient. RESULTS: The achieved hearing preservation for 14 ears was complete in 5, partial in 7, and minimal in 2. Measurable hearing preservation was achieved in 86% overall. Inter-aural analysis revealed that only 2 (subjects 1 and 4) of the 7 patients had preservation results within the same preservation group (complete/partial/minimal). The mean inter-aural preservation difference was 30.7% with a range from 12.4% to 65.2%. CONCLUSIONS: Several factors and techniques have already been identified in the wider literature to explain differences in hearing preservation results in CI. However, despite controlling for known factors, we demonstrate variable inter-aural results. This suggests that there may be more factors beyond the surgeon's control influencing our ability to provide consistent results.


Assuntos
Implante Coclear/estatística & dados numéricos , Perda Auditiva Bilateral/fisiopatologia , Audição , Audiometria de Tons Puros , Limiar Auditivo , Criança , Pré-Escolar , Feminino , Perda Auditiva Bilateral/cirurgia , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
17.
FASEB J ; 20(14): 2600-2, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17077285

RESUMO

Glucocorticoids (GCs) specifically induce apoptosis in malignant lymphoblasts and are thus pivotal in the treatment of acute lymphoblastic leukemia (ALL). However, GC-resistance is a therapeutic problem with an unclear molecular mechanism. We generated approximately 70 GC-resistant sublines from a GC-sensitive B- and a T-ALL cell line and investigated their mechanisms of resistance. In response to GCs, all GC-resistant subclones analyzed by real-time polymerase chain reaction (PCR) showed a deficient up-regulation of the GC-receptor (GR) and its downstream target, GC-induced leucine zipper. This deficiency in GR up-regulation was confirmed by Western blotting and on retroviral overexpression of GR in resistant subclones GC-sensitivity was restored. All GC-resistant subclones were screened for GR mutations using denaturing high-pressure liquid chromatography (DHPLC), DNA-fingerprinting, and fluorescence in situ hybridization (FISH). Among the identified mutations were some previously not associated with GC resistance: A484D, P515H, L756N, Y663H, L680P, and R714W. This approach revealed three genotypes, complete loss of functional GR in the mismatch repair deficient T-ALL model, apparently normal GR genes in B-ALLs, and heterozygosity in both. In the first genotype, deficiency in GR up-regulation was fully explained by mutational events, in the second by a putative regulatory defect, and in the third by a combination thereof. In all instances, GC-resistance occurred at the level of the GR in both models.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Glucocorticoides/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Linhagem Celular Tumoral , Reparo de Erro de Pareamento de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Glucocorticoides/metabolismo , Humanos , Mutação , Receptores de Glucocorticoides/genética , Fatores de Transcrição/metabolismo
18.
Cancer Res ; 65(21): 9712-8, 2005 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16266991

RESUMO

Glucocorticoids are pivotal in the treatment of children with acute lymphoblastic leukemia (ALL) and have significant antileukemic effects in the majority of children. However, clinical resistance is a significant problem. Although cell line models implicate somatic mutations and loss of heterozygosity (LOH) of the glucocorticoid receptor (GR) gene as a mechanism of in vitro glucocorticoid resistance, the relevance of this mechanism as a cause of clinical resistance in children with ALL is not known. Mutational screening of all coding exons of the GR gene and LOH analyses were done in a large cohort of relapsed ALL. We show that somatic mutations and LOH of the GR rarely contribute to relapsed disease in children with ALL. However, we report the second case of ALL with a somatic mutation of the GR involving a 29-bp deletion in exon 8 and resulting in a truncated protein with loss of part of the ligand-binding domain. There was no evidence of a remaining wild-type allele. Allele-specific PCR detected the mutated clone at day 28 after presentation, which persisted at a low level throughout the disease course before relapse several years later. We hypothesize that the mutated allele present in a leukemic subclone at initial diagnosis was selected for during remission induction with glucocorticoids and contributed to the emergence of a glucocorticoid-resistant cell population.


Assuntos
Perda de Heterozigosidade , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Glucocorticoides/genética , Alelos , Medula Óssea/patologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Estudos de Coortes , Éxons , Deleção de Genes , Humanos , Repetições de Microssatélites/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisolona/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Educ Prim Care ; 17(4): 334-341, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-28240128

RESUMO

WHAT IS ALREADY KNOWN IN THIS AREA • Basic training courts for general; practice trainers; do not always meet the demands for the level of 'professionalition' expected. • Many regions now run university-accredited teaching bourses, some of which advocate compulsion. WHAT THIS WORK ADDS • This work has shown that a mandatory course is generally accepted by participants. • Organisational infrastructure needs to be efficient. SUGGESTIONS FOR FUTURE RESEARCH • The effects on trainer recruitment need to be monitored and studied. • The effects on further individual continuing professional development in terms of following this initial course towards a diploma or higher degree.

20.
World Neurosurg ; 93: 490.e13-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27449685

RESUMO

BACKGROUND: Pituitary carcinoma is defined by either metastases outside the central nervous system or noncontiguous foci within the central nervous system. This case report details the first documented case of a pathologically isolated follicle-stimulating hormone-secreting pituitary carcinoma and its presentation of metastasis. CASE DESCRIPTION: A 63-year-old man developed intrascapular pain radiating up his neck to his occiput. He had undergone a transsphenoidal hypophysectomy 2 years previously for an atypical pituitary macroadenoma. Subsequent magnetic resonance imaging identified a focal, solitary, well-circumscribed, homogeneous T2 high-signal intradural, extramedullary enhancing mass at C2-3 in a right ventral parasagittal location, extending toward the exit foramina. On surgical excision with a laminectomy, the mass demonstrated a morphologic appearance of a malignant neuroendocrine tumor with an immunoprofile similar to the original atypical pituitary adenoma. This was in keeping with metastatic disease secondary to a follicle-stimulating hormone-secreting pituitary carcinoma. CONCLUSIONS: Although rare, metastatic spread is recognized in patients with atypical pituitary adenoma. This should form the differential diagnosis for such patients presenting with symptoms that could be attributed to metastatic lesions within the neuraxis. In these patients, who undergo regular surveillance in joint neuroendocrine clinics, more urgent investigation of new spinal pain should be instigated to exclude metastatic disease.


Assuntos
Adenoma Hipofisário Secretor de ACT/patologia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/patologia , Adenoma/cirurgia , Vértebras Cervicais/cirurgia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia , Adenoma/complicações , Vértebras Cervicais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Radiculopatia/prevenção & controle , Neoplasias da Coluna Vertebral/patologia , Resultado do Tratamento
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