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1.
Ophthalmology ; 131(7): 759-770, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38199528

RESUMO

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Anti-Hipertensivos , Glaucoma de Ângulo Aberto , Pressão Intraocular , Mitomicina , Qualidade de Vida , Trabeculectomia , Acuidade Visual , Campos Visuais , Humanos , Trabeculectomia/métodos , Masculino , Pressão Intraocular/fisiologia , Feminino , Acuidade Visual/fisiologia , Idoso , Anti-Hipertensivos/uso terapêutico , Campos Visuais/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Inquéritos e Questionários , Seguimentos , Resultado do Tratamento , Tonometria Ocular , Perfil de Impacto da Doença , Soluções Oftálmicas , Alquilantes/administração & dosagem , Idoso de 80 Anos ou mais
2.
Nat Rev Mol Cell Biol ; 10(4): 293-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19190670

RESUMO

Myofibril assembly results in a regular array of identical sarcomeres in striated muscle. Sarcomere structure is conserved across the animal kingdom, which implies that the mechanisms of myofibril assembly are also likely to be conserved. Recent advances from model genetic systems and insights from stress fibre cell biology have shed light on the mechanisms that set sarcomere spacing and the initial assembly of sarcomere arrays. We propose a model of integrin-dependent cell-matrix adhesion as the starting point for myofibrillogenesis.


Assuntos
Integrinas/metabolismo , Desenvolvimento Muscular , Animais , Junções Célula-Matriz/metabolismo , Sarcômeros/metabolismo
3.
Qual Life Res ; 29(7): 1935-1946, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32080789

RESUMO

PURPOSE: The validity and responsiveness of the EQ-5D-3L in visual conditions has been questioned, inspiring development of a vision 'bolt-on' domain (EQ-5D-3L + VIS). Developments in preference-based measures (PBM) also includes the EQ-5D-5L and the ICECAP-O capability wellbeing measure. This study aimed to examine the construct validity and responsiveness of the EQ-5D-3L, EQ-5D-5L, EQ-5D-3L + VIS and ICECAP-O in cataract surgery patients for the first time, to inform choice of PBM for economic evaluation in this population. METHODS: The analyses used data from the UK Predict-CAT cataract surgery cohort study. PBMs and the Cat-PROM5 [a validated measure of cataract quality of life (QOL)] were completed before surgery and 4-8 weeks after. Construct validity was assessed using correlations and known-group differences evaluated using regression. Responsiveness was evaluated using effect sizes and analysis of variance to compare change scores between groups, defined by patient-reported and clinical outcomes. RESULTS: The sample comprised 1315 patients at baseline. No PBMs were associated with visual acuity and only the ICECAP-O (Spearman's rs = - 0.35), EQ-5D-3L + VIS (rs = - 0.42) and EQ-5D-5L (Value Set for England rs = - 0.31) correlated at least moderately with the Cat-PROM5. Effect sizes of change were consistently largest for the EQ-5D-3L + VIS (range 0.34-0.41), followed by the ICECAP-O (range 0.20-0.34). Results indicated no improvement in responsiveness using the EQ-5D-5L (range 0.13-0.16) compared to the EQ-5D-3L (range 0.17-0.20). CONCLUSIONS: Whilst no PBMs comprehensively demonstrated evidence of construct validity and responsiveness in cataract surgery patients, the ICECAP-O was the most responsive generic PBM to improvements in QOL. Surprisingly the EQ-5D-5L was not more responsive than the EQ-5D-3L in this setting.


Assuntos
Catarata/psicologia , Catarata/terapia , Nível de Saúde , Qualidade de Vida/psicologia , Acuidade Visual/fisiologia , Adulto , Idoso , Extração de Catarata/métodos , Estudos de Coortes , Análise Custo-Benefício , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
4.
J Med Ethics ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958695

RESUMO

PURPOSE: The purported benefits and risks of immediately sequential bilateral cataract surgery (ISBCS) have been well described, yet the procedure remains controversial among UK ophthalmologists. As many of the controversies of ISBCS are underpinned by ethical dilemmas, the aim of this work was to explore the ethical perspectives of ISBCS from a variety of stakeholder viewpoints. METHOD: A semi-structured independent stakeholder meeting was convened at the Royal College of Ophthalmologists London headquarters in June 2018. In total, 29 stakeholders attended the meeting. The professional characteristics of stakeholders included but were not limited to: ophthalmologists (9), patients (5), religious leaders (4), ethicists (2), lawyers (2) and commissioners (1). Thematic qualitative analysis using methodology proposed by Braun and Clarke was conducted on the resultant transcript of the discussion. RESULTS: Themes identified include: (1) beneficence and non-maleficence (patient benefits, patient risks, the uncertainties of risk, patient interpretation of the risk-benefit analysis); (2) autonomy (informed consent, the barriers to communication); (3) distributive justice (the allocation of resources: the individual vs the collective). CONCLUSION: This analysis provides a reference point for the ethical factors surrounding ISBCS. The stakeholders concluded that this approach was an ethical undertaking provided patient autonomy was appropriately attained. This requires a patient's interpretation of the risk-benefit balance, which must include an understanding of the low but unquantifiable risk of severe complications. A surgeon must aim to minimise risks through the adaption of accepted surgical protocols and by performing appropriate patient selection. Currently, cost savings to healthcare that may occur following the implementation of ISBCS should be considered a secondary benefit of the protocol.

5.
Ophthalmology ; 126(1): 13-18, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153943

RESUMO

PURPOSE: To compare methods for evaluating refractive outcomes after cataract surgery to detect outliers. DESIGN: Case series database study of the evaluation of diagnostic technology. PARTICIPANTS: Consecutive patients who had uneventful cataract operations over a 5-year period. METHODS: The intended and postoperative refractive outcome and differences between these were analyzed as a spherical equivalent, cylinder, and spherocylinder. The average keratometry and differences between steep and flat keratometric meridians were used to calculate the intended refractive error. MAIN OUTCOME MEASURES: Outliers were defined as patients for whom the difference between the intended and postoperative refractive errors was more than 3 standard deviations (SDs) away from the mean. RESULTS: A total of 9000 patients were included. Twelve patients had missing data and were excluded. The mean intended refractive outcome was -0.12+0.12×2 (95% lower confidence limit [LCL], -1.94+1.06×44; 95% upper confidence limit [UCL], +0.77+1.05×140). The actual postoperative refractive error was -0.30+0.47×6 (95% LCL, -2.36+1.31×36; 95% UCL, +1.00+1.18×148) with a difference from the intended of -0.18+0.35×7 (95% LCL, -1.91+1.22×38; 95% UCL, +0.75+1.09×145). Treating the components of the refractive error independently, outliers were observed in 82 eyes (0.91%) based on the sphere, 46 eyes (0.51%) based on the spherical equivalent, 115 eyes (1.28%) based on treating the cylinder as a scalar, and 76 eyes (0.85%) based on treating the cylinder as a vector. When the differences between the intended and postoperative refractive errors were calculated as a compound spherocylinder, outliers were observed for 233 eyes (2.59%). CONCLUSIONS: Treating the intended refractive outcome as a spherocylinder improves the precision for detecting clinically significant refractive outliers.


Assuntos
Córnea/fisiopatologia , Implante de Lente Intraocular , Facoemulsificação/métodos , Pseudofacia/fisiopatologia , Refração Ocular/fisiologia , Erros de Refração/fisiopatologia , Idoso , Comprimento Axial do Olho , Biometria , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Acuidade Visual/fisiologia
6.
Retina ; 38(2): 334-342, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28221255

RESUMO

BACKGROUND/PURPOSE: To audit variations in primary rhegmatogenous retinal detachment (RD) anatomical failure rates between surgeons, grades of surgeons, and techniques of RD surgery. METHODS: Clinical data of a total of 5,857 eyes undergoing primary RD surgery, from 2000 to 2013 were retrospectively extracted from 15 centers using the same commercially available electronic medical record system, from three vitreoretinal units using an in-house electronic medical record, and from the British and Eire Association of Vitreoretinal Surgeons online registry. RESULTS: The 5,857 primary RD operations were performed by 117 surgeons: 3,349 (57.2%) by consultants, 520 (8.9%) by independent nonconsultants, and 1,988 (33.9%) by trainees. Surgery comprised pars plana vitrectomy for 4,666 (79.7%) operations, scleral buckle for 815 (13.9%), and pars plana vitrectomy + scleral buckle for 376 (6.4%). The RD reoperation rate at 6 months after primary surgery was 13.9% (725/5,202) and did not differ significantly between consultants and trainees (P = 0.382). For surgeons contributing ≥50 cases, the mean (range) reoperation rates were 13.1% (6.7%-26.8%), 15.1% (11.3%-18.2%), and 15.3% (9.4%-22.1%) for consultants, independent nonconsultants, and trainee surgeons, respectively. The scleral buckle failure rate was not significantly different from pars plana vitrectomy (P = 0.095). Data were not adjusted for case-mix complexity. CONCLUSION: The grades of surgeons and the technique of surgery were not associated with a significant difference in primary unadjusted RD failure rates.


Assuntos
Oftalmologistas/estatística & dados numéricos , Oftalmologia/organização & administração , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Descolamento Retiniano/cirurgia , Sociedades Médicas/estatística & dados numéricos , Cirurgia Vitreorretiniana , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Reino Unido/epidemiologia
7.
J Cell Sci ; 128(18): 3386-97, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26251439

RESUMO

Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains. Kinase domain 1 bound Bällchen (Ball, an active kinase), and both kinase domains 1 and 2 bound MASK (a 400-kDa protein with ankyrin repeats). Ball was present in the Z-disc and M-line of the indirect flight muscle (IFM) and was diffusely distributed in the sarcomere. MASK was present in both the M-line and the Z-disc. Reducing expression of Ball or MASK by siRNA resulted in abnormalities in the IFM, including missing M-lines and multiple Z-discs. Obscurin was still present, suggesting that the kinase domains act as a scaffold binding Ball and MASK. Unlike obscurin in vertebrate skeletal muscle, Drosophila obscurin is necessary for the correct assembly of the IFM sarcomere. We show that Ball and MASK act downstream of obscurin, and both are needed for development of a well defined M-line and Z-disc. The proteins have not previously been identified in Drosophila muscle.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Voo Animal/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/ultraestrutura , Proteínas Quinases/metabolismo , Animais , Proteínas de Ligação a DNA/química , Proteínas de Drosophila/química , Proteínas Musculares/química , Protamina Quinase , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Quinases/química , Sarcômeros/metabolismo , Sarcômeros/ultraestrutura
8.
PLoS Genet ; 10(2): e1004166, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24586196

RESUMO

During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin.


Assuntos
Citoesqueleto de Actina/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Drosophila/genética , Desenvolvimento Muscular/genética , Sarcômeros/genética , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Diferenciação Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Desenvolvimento Muscular/fisiologia , Miocárdio/metabolismo , Miofibrilas/genética , Miofibrilas/metabolismo , Miosinas/genética , Sarcômeros/fisiologia , Sarcômeros/ultraestrutura
9.
Ophthalmology ; 123(8): 1711-1715, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27342788

RESUMO

PURPOSE: To investigate time to pseudophakic retinal detachment (RD) after cataract surgery with posterior capsule rupture (PCR) to provide an evidence-based guide for postoperative management. DESIGN: Retrospective case series. PARTICIPANTS: A total of 61 907 eyes of 46 824 patients undergoing cataract surgery. METHODS: Subanalysis of the United Kingdom Royal College of Ophthalmologists' National Ophthalmology Database from 13 sites where data on both cataract and vitreoretinal surgery were recorded on the same electronic medical records system. Overall, 61 907 cataract operations were performed between October 2006 and August 2010. Analyses were restricted to cases with at least 3 months of potential postoperative follow-up. RESULTS: Pseudophakic RD surgery was performed on 131 eyes of 129 patients (0.21%; 95% confidence interval [CI], 0.18%-0.25%). Of these, 36 were in eyes that had PCR during cataract surgery (3.27%; 95% CI, 2.37%-4.50%) and 95 were in eyes that did not have PCR (0.16%; 95% CI, 0.13%-0.19%). For eyes that progressed to RD surgery, the median time to pseudophakic RD surgery was 44 days for eyes with PCR, and 6.3 months for eyes without PCR. For all eyes (both with and without PCR), pseudophakic RD occurred earlier in cases performed by a trainee cataract surgeon. CONCLUSIONS: Pseudophakic RD occurs earlier after cataract surgery complicated by PCR. Surgeon grade is a risk factor for pseudophakic RD. Posterior vitreous detachment and RD symptoms should be discussed with patients who undergo cataract surgery and have PCR to facilitate early attendance, and careful dilated postoperative examination for retinal tears is recommended in the first 2 months after surgery.


Assuntos
Extração de Catarata/efeitos adversos , Bases de Dados Factuais , Ruptura da Cápsula Posterior do Olho/etiologia , Pseudofacia/etiologia , Descolamento Retiniano/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura da Cápsula Posterior do Olho/cirurgia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Fatores de Risco , Medicina Estatal , Fatores de Tempo , Reino Unido
10.
Ophthalmologica ; 235(3): 157-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26863026

RESUMO

PURPOSE: To characterise the learning curve of primary retinal detachment (RD) repair for trainee surgeons and monitor the outcomes of surgery for established surgeons. PROCEDURES: Primary RD operations were analysed sequentially using the cumulative sum (CUSUM) and the sequential probability ratio test (SPRT). RESULTS: 359 analysed cases of primary RD were audited with a recurrent RD (ReRD) rate of 14.7%. The individual rate of ReRD ranged from 9.4 to 17.4% (p = 0.74). SPRT and CUSUM analyses showed that ReRD occurred at random when operated by senior surgeons but a learning curve was discernible for junior surgeons. There was a trend for a higher proportion of ReRD caused by untreated breaks in cases operated by junior surgeons (p = 0.75). CONCLUSION: SPRT and CUSUM are useful methods to monitor surgical outcomes and should be included in audits of sequential operations such as RD. Trainee surgeons experience a quantifiable learning curve.


Assuntos
Competência Clínica/normas , Avaliação Educacional , Curva de Aprendizado , Procedimentos Cirúrgicos Oftalmológicos/educação , Descolamento Retiniano/cirurgia , Crioterapia , Tamponamento Interno , Humanos , Corpo Clínico Hospitalar , Monitorização Intraoperatória , Garantia da Qualidade dos Cuidados de Saúde , Recurvamento da Esclera , Vitrectomia
11.
J Cell Sci ; 126(Pt 1): 139-48, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23178940

RESUMO

During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding exon inserted into the single Drosophila muscle myosin heavy chain gene, Mhc. The weeP26 IFM sarcomeres have a unique MHC-GFP-labelling pattern restricted to the sarcomere core, explained by non-translation of the GFP exon following alternative splicing. Characterisation of wild-type IFM MHC mRNA confirmed the presence of an alternately spliced isoform, expressed earlier than the major IFM-specific isoform. The two wild-type IFM-specific MHC isoforms differ by the presence of a C-terminal 'tailpiece' in the minor isoform. The sequential expression and assembly of these two MHCs into developing thick filaments suggest a role for the tailpiece in initiating A-band formation. The restriction of the MHC-GFP sarcomeric pattern in weeP26 is lifted when the IFM lack the IFM-specific myosin binding protein flightin, suggesting that it limits myosin dissociation from thick filaments. Studies of flightin binding to developing thick filaments reveal a progressive binding at the growing thick filament tips and in a retrograde direction to earlier assembled, proximal filament regions. We propose that this flightin binding restricts myosin molecule incorporation/dissociation during thick filament assembly and explains the location of the early MHC isoform pattern in the IFM A-band.


Assuntos
Proteínas de Drosophila/metabolismo , Músculo Esquelético/metabolismo , Isoformas de Proteínas/metabolismo , Processamento Alternativo/genética , Processamento Alternativo/fisiologia , Animais , Drosophila , Proteínas de Drosophila/genética , Éxons/genética , Filaminas , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Miosinas/genética , Miosinas/metabolismo , Isoformas de Proteínas/genética , Sarcômeros/metabolismo
12.
Retina ; 35(8): 1615-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25830695

RESUMO

PURPOSE: To report pragmatic outcomes from a database study of epiretinal membrane surgery. METHODS: Prospective anonymized clinical audit data from electronic medical records were pooled over 10 years into a national database, from 1,131 primary epiretinal membrane operations, by 69 surgeons, in 16 U.K. vitreoretinal units. RESULTS: The median age of 1,131 patients was 71.6 years. A pars plana vitrectomy and epiretinal membrane peel were combined with internal limiting membrane peel in 17.0% of operations, and cataract surgery in 49.9%. Use of general anesthesia declined from 94.1% in 2001 to 28.9% in 2010. One or more intraoperative complication occurred in 9.8% (8.1% excluding cataract surgery complications). The median preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity improved from 0.60 to 0.30 (Snellen 20/80-20/40) after a median follow-up of 7.0 months; 41.7% of eyes improved ≥0.30 logMAR units (approximately 2 Snellen's lines). The percentages of eyes undergoing subsequent surgery were 3.3%, 1.0%, 0.4%, and 0.8% for epiretinal membrane, retinal detachment, macular hole, and other vitreoretinal indications, respectively. Excluding pseudophakic eyes, 51.7%, 73.2%, and 76.2% of eyes underwent cataract surgery within 1 year, 2 year, and 3 years respectively. CONCLUSION: These results may help vitreoretinal surgeons to benchmark their surgical outcomes, and patients to assess the risks and benefits of surgery.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Membrana Epirretiniana/cirurgia , Auditoria Médica , Oftalmologia/organização & administração , Cirurgia Vitreorretiniana/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/estatística & dados numéricos , Membrana Epirretiniana/fisiopatologia , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/epidemiologia , Perfurações Retinianas/cirurgia , Sociedades Médicas/organização & administração , Reino Unido/epidemiologia , Acuidade Visual/fisiologia
13.
J Exp Child Psychol ; 136: 30-41, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25897958

RESUMO

Smiling and laughing appear very early during the first year of life, but little is known about how infants come to appraise a stimulus as humorous. This short-term longitudinal study explored infant humor perception from 5 to 7 months of age as a function of parental affect during an absurd event. Using a within-participants design, parents alternated smiling/laughing with emotional neutrality while acting absurdly toward their infants. Group comparisons showed that infants (N = 37) at all ages smiled at the event regardless of parental affect but did so significantly longer at 5 and 6 months, and more often and sooner at 7 months, when parents provided humor cues. Similarly, sequential analyses revealed that after gazing at the event, 7-month-olds were more likely to smile at it only when parents provided humor cues and were comparatively more likely to look away when parents were neutral. Thus, starting at 5 months of age, parental affect influenced infants' affect toward an absurd event, an effect that was magnified at 7 months. These results are discussed in the context of emotional contagion, regulation, and the emergence of social referencing.


Assuntos
Afeto , Comportamento do Lactente/psicologia , Riso/psicologia , Pais/psicologia , Sinais (Psicologia) , Expressão Facial , Feminino , Humanos , Lactente , Masculino
14.
J Cell Sci ; 125(Pt 14): 3367-79, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22467859

RESUMO

Obscurin (also known as Unc-89 in Drosophila) is a large modular protein in the M-line of Drosophila muscles. Drosophila obscurin is similar to the nematode protein UNC-89. Four isoforms are found in the muscles of adult flies: two in the indirect flight muscle (IFM) and two in other muscles. A fifth isoform is found in the larva. The larger IFM isoform has all the domains that were predicted from the gene sequence. Obscurin is in the M-line throughout development of the embryo, larva and pupa. Using P-element mutant flies and RNAi knockdown flies, we have investigated the effect of decreased obscurin expression on the structure of the sarcomere. Embryos, larvae and pupae developed normally. In the pupa, however, the IFM was affected. Although the Z-disc was normal, the H-zone was misaligned. Adults were unable to fly and the structure of the IFM was irregular: M-lines were missing and H-zones misplaced or absent. Isolated thick filaments were asymmetrical, with bare zones that were shifted away from the middle of the filaments. In the sarcomere, the length and polarity of thin filaments depends on the symmetry of adjacent thick filaments; shifted bare zones resulted in abnormally long or short thin filaments. We conclude that obscurin in the IFM is necessary for the development of a symmetrical sarcomere in Drosophila IFM.


Assuntos
Drosophila/fisiologia , Proteínas Musculares/fisiologia , Músculo Esquelético/fisiologia , Sarcômeros/fisiologia , Animais , Drosophila/genética , Drosophila/metabolismo , Feminino , Expressão Gênica , Imunoprecipitação , Masculino , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Isoformas de Proteínas , Sarcômeros/metabolismo
15.
Ophthalmology ; 121(3): 643-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23978624

RESUMO

PURPOSE: To describe rhegmatogenous retinal detachment (RD) surgery. DESIGN: National Ophthalmology Database study. PARTICIPANTS: A total of 3403 eyes from 3321 patients undergoing primary RD surgery. METHODS: Participating centers prospectively collected clinical data using a single electronic medical record system, with automatic extraction of anonymized data to a national database, from 2002 to 2010. MAIN OUTCOME MEASURES: Description of the primary procedures performed, intraoperative complication rate, and proportion of eyes undergoing subsequent RD or cataract surgery. We undertook an exploratory analysis of change in visual acuity (VA) using the data available. RESULTS: Of 3403 operations, 2693 (79.1%) were pars plana vitrectomy (PPV), 413 (12.1%) were retinopexy with a scleral buckle (SB), and 297 (8.7%) were PPV with an SB (PPV-SB). For PPV and PPV-SB, 18.8% were with hexafluoroethane, 12.1% were with perfluoropropane, 43.1% were with sulfahexafluoride, 1.8% were with air, 17.9% were with silicone oil, and 10.7% were with cataract surgery. Within 1 year of vitrectomy, 52.1% of phakic eyes had undergone cataract surgery. For all RD operations combined (and excluding cataract surgery complications), 5.1% had 1 or more intraoperative complication, 13.0% underwent further RD surgery, and 8.3% had silicone oil in situ at last review. The RD reoperation rate was 13.3%, 12.3%, and 14.5% for PPV, SB, and PPV-SB, respectively. For 961 eyes with a baseline and final VA measurement, the median presenting logarithm of the minimum angle of resolution VA improved from 1.0 to 0.5 (20/200-20/63) after a median follow-up of 0.6 years. CONCLUSIONS: These results may help vitreoretinal surgeons to benchmark their intraoperative complication rate and reoperation rate and to compare their surgical techniques with their peers'. They suggest that the benefits of RD surgery greatly outweigh the risks.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Programas Nacionais de Saúde/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , Descolamento Retiniano/cirurgia , Cirurgia Vitreorretiniana , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ar , Extração de Catarata , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Tamponamento Interno , Feminino , Fluorocarbonos/administração & dosagem , Humanos , Lactente , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reoperação , Descolamento Retiniano/fisiopatologia , Óleos de Silicone/administração & dosagem , Reino Unido , Acuidade Visual/fisiologia , Cirurgia Vitreorretiniana/estatística & dados numéricos , Adulto Jovem
16.
Ophthalmology ; 120(3): 629-634, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23211634

RESUMO

PURPOSE: To study macular hole (MH) surgery in terms of baseline demographics, intraoperative complications, post-vitrectomy cataract, reoperation, and visual outcome. DESIGN: National Ophthalmology Database study. PARTICIPANTS: A total of 1078 eyes from 1045 patients undergoing primary MH surgery. METHODS: Participating centers prospectively collected clinical data using a single electronic medical record (EMR) system, with automatic extraction of anonymized data to a national database, over 8 years. The following data were extracted for eyes undergoing MH surgery: demographics, procedure elements, intraoperative complications, visual acuity (VA), and further surgery. MAIN OUTCOME MEASURES: Description of the primary procedures performed, intraoperative complication rate, change in VA, proportion of eyes undergoing subsequent surgery for persisting MH, cataract, or retinal detachment. RESULTS: The median age was 70.3 years, with a 2.2:1 female preponderance. All operations included a pars plana vitrectomy (PPV)-41.1% with hexafluoroethane (C2F6), 25.6% with perfluoropropane (C3F8), 24.5% with sulfahexafluoride (SF6), 2.2% with air, and 0.4% with silicone oil. A PPV was combined with internal limiting membrane (ILM) peel in 94.1% and cataract surgery in 40.5%. One or more intraoperative complications occurred in 12.4%. The median presenting logarithm of the minimum angle of resolution (logMAR) VA improved from 0.80 to 0.50 after a median follow-up of 0.6 years; 57.8% of eyes improved ≥0.30 logMAR units (∼2 Snellen lines). The choice of gas tamponade did not significantly influence the visual outcome, but eyes undergoing ILM peel were significantly more likely to gain ≥0.30 logMAR units, as were eyes with poor presenting VA. Subsequently, 4.2% of eyes underwent repeat surgery for MH and 2.4% for retinal detachment, and, excluding pseudophakic eyes, 64.6% underwent cataract surgery within 1 year. CONCLUSIONS: This study provides pooled, anonymized data on the demographics, complications, and visual outcome of MH surgery. This may enable vitreoretinal surgeons to benchmark their case-mix and outcomes, and facilitate risk-benefit and cost-benefit analyses.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , Perfurações Retinianas/cirurgia , Cirurgia Vitreorretiniana/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Tamponamento Interno , Feminino , Fluorocarbonos/administração & dosagem , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Reoperação , Perfurações Retinianas/epidemiologia , Hexafluoreto de Enxofre/administração & dosagem , Reino Unido/epidemiologia , Acuidade Visual/fisiologia , Vitrectomia , Adulto Jovem
17.
Methods ; 56(1): 78-86, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22037247

RESUMO

We describe our methods for analysing muscle function in a whole intact small insect, taking advantage of a simple flexible optical beam to produce an inexpensive transducer with wide application. We review our previous data measuring the response to a single action potential driven muscle twitch to explore jumping behaviour in Drosophila melanogaster. In the fruitfly, where the sophisticated and powerful genetic toolbox is being widely employed to investigate neuromuscular function, we further demonstrate the use of the apparatus to analyse in detail, within whole flies, neuronal and muscle mutations affecting activation of muscle contraction in the jump muscle. We have now extended the use of the apparatus to record the muscle forces during larval and other aspects of adult locomotion. The robustness, simplicity and versatility of the apparatus are key to these measurements.


Assuntos
Drosophila melanogaster , Contração Muscular/fisiologia , Animais , Voo Animal/fisiologia , Contração Muscular/genética , Mutação , Transdutores , Caminhada/fisiologia
19.
Br J Ophthalmol ; 107(4): 488-494, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34764082

RESUMO

AIM: To investigate effect of patient age, gender, comorbidities and surgeon on refractive outcomes following cataract surgery. METHODS: Study population: patients on UK national ophthalmic cataract database on cataract operations undertaken between 1 April 2010 and 31 August 2018. Variables examined included gender, age, diabetic retinopathy, glaucoma, high myopia, inherited retinal disease, optic nerve disease, uveitis, pseudoexfoliation, vitreous opacities, retinal pathology, cataract type, previous surgery and posterior capsular rupture. A multivariate normal cross-classified model was fitted to the refractive outcome using Markov Chain Monte Carlo (MCMC) methods with diffuse priors to approximate maximum likelihood estimation. A MCMC chain was generated with a burn-in of 5000 iterations and a monitoring chain of 50 000 iterations. RESULTS: 490 987 cataract operations were performed on 351 864 patients by 2567 surgeons. Myopic and astigmatic errors were associated with posterior capsule rupture (-0.38/+0.04×72), glaucoma (-0.10/+0.05×95), previous vitrectomy (-0.049/+0.03×66) and high myopia (-0.07/+0.03×57). Hyperopic and astigmatic errors were associated with diabetic retinopathy (+0.08/+0.03×104), pseudoexfoliation (+0.07/+0.01×158), male gender (+0.12/+0.05×91) and age (-0.01/+0.06×97 per increasing decade). Inherited retinal disease, optic nerve disease, previous trabeculectomy, uveitis, brunescent/white cataract had no significant impact on the error of the refractive outcome. The effect of patient gender and comorbidity was additive. Surgeons only accounted for 4% of the unexplained variance in refractive outcome. CONCLUSION: Patient comorbidities and gender account for small but statistically significant differences in refractive outcome, which are additive. Surgeon effects are very small.


Assuntos
Catarata , Retinopatia Diabética , Glaucoma , Miopia , Doenças do Nervo Óptico , Facoemulsificação , Doenças Retinianas , Cirurgiões , Humanos , Masculino , Retinopatia Diabética/complicações , Refração Ocular , Catarata/complicações , Comorbidade , Doenças Retinianas/cirurgia , Corpo Vítreo , Doenças do Nervo Óptico/complicações , Estudos Retrospectivos , Facoemulsificação/métodos
20.
Eye (Lond) ; 37(8): 1633-1639, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36002508

RESUMO

BACKGROUND/OBJECTIVES: Posterior Capsule Opacification (PCO) is the most common long-term post-operative adverse occurrence after cataract surgery often requiring treatment with YAG laser posterior capsulotomy. This study aimed to identify potential risk factors, known at the time of cataract surgery, that influence the development of PCO. SUBJECT/METHODS: A retrospective study of publicly funded cataract surgery from The Royal College of Ophthalmologists' National Ophthalmology Database. Eligible for analysis were 500,872 cataract operations performed in 41 participating centres. RESULTS: The 500,872 operations were performed on 243,167 (48.5%) left eyes and 257,705 (51.5%) right eyes from 373,579 patients by 2196 surgeons. Post-cataract PCO was recorded for 61,778 (12.3%) eyes and the six month, one, three, five and nine year observed rates of PCO were 2.3%, 4.4%, 19.7%, 34.0% and 46.9% respectively. Different PCO profiles were observed between IOL materials and the identified risk factors that increased the risk of developing PCO included hydrophilic IOL material, axial length >26 mm, the presence of high myopia and implantation of lower IOL powers and previous vitrectomy surgery, along with younger age and female gender. CONCLUSIONS: Many factors influence the development of PCO relating to the patient, the eye, the lens and the surgery. Some factors are modifiable such as IOL material, therefore the opportunity exists to attempt to reduce PCO rates, benefitting patients and the UK NHS.


Assuntos
Opacificação da Cápsula , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Oftalmologistas , Oftalmologia , Humanos , Feminino , Opacificação da Cápsula/epidemiologia , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/cirurgia , Implante de Lente Intraocular/efeitos adversos , Lentes Intraoculares/efeitos adversos , Estudos Retrospectivos , Cápsula do Cristalino/cirurgia , Catarata/etiologia , Fatores de Risco , Complicações Pós-Operatórias/etiologia
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