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1.
J Biol Chem ; 299(2): 102806, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36529289

RESUMO

Karyopherin-ß2 (Kapß2) is a nuclear-import receptor that recognizes proline-tyrosine nuclear localization signals of diverse cytoplasmic cargo for transport to the nucleus. Kapß2 cargo includes several disease-linked RNA-binding proteins with prion-like domains, such as FUS, TAF15, EWSR1, hnRNPA1, and hnRNPA2. These RNA-binding proteins with prion-like domains are linked via pathology and genetics to debilitating degenerative disorders, including amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy. Remarkably, Kapß2 prevents and reverses aberrant phase transitions of these cargoes, which is cytoprotective. However, the molecular determinants of Kapß2 that enable these activities remain poorly understood, particularly from the standpoint of nuclear-import receptor architecture. Kapß2 is a super-helical protein comprised of 20 HEAT repeats. Here, we design truncated variants of Kapß2 and assess their ability to antagonize FUS aggregation and toxicity in yeast and FUS condensation at the pure protein level and in human cells. We find that HEAT repeats 8 to 20 of Kapß2 recapitulate all salient features of Kapß2 activity. By contrast, Kapß2 truncations lacking even a single cargo-binding HEAT repeat display reduced activity. Thus, we define a minimal Kapß2 construct for delivery in adeno-associated viruses as a potential therapeutic for amyotrophic lateral sclerosis/frontotemporal dementia, multisystem proteinopathy, and related disorders.


Assuntos
Chaperonas Moleculares , Fragmentos de Peptídeos , Príons , Proteína FUS de Ligação a RNA , beta Carioferinas , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , beta Carioferinas/química , beta Carioferinas/genética , beta Carioferinas/metabolismo , Linhagem Celular , Dependovirus/metabolismo , Demência Frontotemporal/metabolismo , Demência Frontotemporal/terapia , Técnicas In Vitro , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Príons/química , Príons/metabolismo , Deficiências na Proteostase/metabolismo , Deficiências na Proteostase/terapia , Proteína FUS de Ligação a RNA/química , Proteína FUS de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ligação Proteica
2.
Cancer ; 129(6): 867-877, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36653915

RESUMO

BACKGROUND: Tobacco use is a major risk factor for developing head and neck squamous cell carcinoma (HNSCC). However, the prognostic associations with smoking cessation are limited. The authors assessed whether smoking cessation and increased duration of abstinence were associated with improved overall (OS) and HNSCC-specific survival. METHODS: Clinicodemographic and smoking data from patients with HNSCC at Princess Margaret Cancer Center (2006-2019) were prospectively collected. Multivariable Cox and Fine and Gray competing-risk models were used to assess the impact of smoking cessation and duration of abstinence on overall mortality and HNSCC-specific/noncancer mortality, respectively. RESULTS: Among 2482 patients who had HNSCC, former smokers (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.58-0.87; p = .001; N = 841) had a reduced risk of overall mortality compared with current smokers (N = 931). Compared with current smokers, former smokers who quit >10 years before diagnosis (long-term abstinence; n = 615) had the most improved OS (aHR, 0.72; 95% CI, 0.56-0.93; p = .001). The 5-year actuarial rates of HNSCC-specific and noncancer deaths were 16.8% and 9.4%, respectively. Former smokers (aHR, 0.71; 95% CI, 0.54-0.95; p = .019) had reduced HNSCC-specific mortality compared with current smokers, but there was no difference in noncancer mortality. Abstinence for >10 years was associated with decreased HNSCC-specific death compared with current smoking (aHR, 0.64; 95% CI, 0.46-0.91; p = .012). Smoking cessation with a longer duration of quitting was significantly associated with reduced overall and HNSCC-specific mortality in patients who received primary radiation. CONCLUSIONS: Smoking cessation before the time of diagnosis reduced overall mortality and cancer-specific mortality among patients with HNSCC, but no difference was observed in noncancer mortality. Long-term abstinence (>10 pack-years) had a significant OS and HNSCC-specific survival benefit.


Assuntos
Neoplasias de Cabeça e Pescoço , Abandono do Hábito de Fumar , Produtos do Tabaco , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Fumar/efeitos adversos , Fumar/epidemiologia
3.
Health Promot Pract ; 24(2): 201-206, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35094594

RESUMO

As cases of COVID-19 began to increase in Ontario, Canada, throughout 2020, early evidence from surveillance and media highlighted disproportionately higher rates of COVID-19 infection, hospitalization and mortality among racialized and low-income populations. This disproportionate impact on underserved populations calls for a shift in approach away from what has traditionally occurred in health protection, that is the use of a universal approach which assumes everyone is affected and benefits equally from the same type and intensity of interventions. In this article, public health agencies are, therefore, being called to consider moving away from using a purely universal approach, often used in the control of communicable diseases, and apply a more tailored approach and use principles of health equity and proportionate universalism to reduce COVID-19 cases and their impacts among underserved groups and address health inequities exacerbated by the pandemic. We highlight examples from York Region Public Health, one of the largest health units in Ontario, to demonstrate areas of possible impact of this paradigm shift. It is clear that with a health equity lens applied to the pandemic response, the impact of COVID-19 can be further reduced and health inequities that predated the global pandemic can improve.


Assuntos
COVID-19 , Equidade em Saúde , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Saúde Pública , Ontário/epidemiologia
4.
Ophthalmic Physiol Opt ; 41(1): 144-156, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33300622

RESUMO

The COVID-19 pandemic has been spreading across the globe for several months. The nature of the virus (SARS-CoV-2) with easy person-to-person transmissions and the severe clinical course observed in some people necessitated unprecedented modifications of everyday social interactions. These included the temporary suspension of considerable elements of clinical teaching at optometry schools worldwide. This article describes the challenges optometry schools were facing in early to mid 2020. The paper highlights the experiences of six universities in five countries on four continents. Strategies to minimise the risk of virus transmission, to ensure safe clinical optometric teaching and how to overcome the challenges presented by COVID-19 are described. An outlook on opportunities to further improve optometric education is provided.


Assuntos
COVID-19/epidemiologia , Optometria/educação , SARS-CoV-2 , Escolas para Profissionais de Saúde/organização & administração , Ensino/organização & administração , COVID-19/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Educação a Distância/métodos , Humanos , Equipamento de Proteção Individual , Distanciamento Físico , Autoaprendizagem como Assunto
5.
Neuromodulation ; 24(8): 1377-1387, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32881193

RESUMO

OBJECTIVES: Translingual neurostimulation (TLNS) with adjunct physical rehabilitation is used to treat balance and gait deficits in several chronic neurological conditions. The purpose of this review is to summarize and appraise the evidence currently available on the portable TLNS device and to assess its potential clinical application. MATERIALS AND METHODS: In this narrative review, MEDLINE, EMBASE, Web of Science, and Google Scholar were searched for primary research investigating the use of portable TLNS devices on any neurologic condition. Data were extracted, reviewed, and appraised with respect to study design, conduct, and reporting. RESULTS: Five randomized controlled trials (RCTs), three quasi-experimental trials, and seven case reports/series were found. Most studies demonstrated improvements in balance and gait deficits secondary to traumatic brain injury and multiple sclerosis, but evidence is also present to a lesser degree for stroke and balance disorder patients. In these studies, the feasibility and safety of TLNS have been convincingly demonstrated. Functional magnetic resonance studies have also suggested a plausible neuroplastic therapeutic mechanism. However, the efficacy of TLNS remains unclear due to bias and confounding within studies, and heterogeneity of results between studies. CONCLUSIONS: TLNS is a promising treatment modality for various chronic neurological conditions that are often refractory to conventional therapy. However, TLNS technology remains largely investigational as high-quality RCTs are still required to elucidate efficacy, optimal dosages, necessary treatment durations, and treatment durability. Further research to develop an appropriate control group is needed for scientifically valid comparisons of TLNS.


Assuntos
Lesões Encefálicas Traumáticas , Acidente Vascular Cerebral , Humanos , Imageamento por Ressonância Magnética , Plasticidade Neuronal , Tecnologia
6.
Optom Vis Sci ; 97(2): 121-127, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32011585

RESUMO

SIGNIFICANCE: This study demonstrated that a semiautomated segmentation method could help inexperienced practitioners to obtain choroidal thickness as good as experienced practitioners. PURPOSE: The purpose of this study was to compare choroidal thickness measurements obtained by semiautomated and manual segmentation methods. METHODS: Optical coherence tomography images of 37 eyes from 37 healthy young subjects acquired by a spectral-domain optical coherence tomography device were reviewed retrospectively. Two naive examiners measured choroidal thickness using manual and semiautomated methods, whereas two experienced examiners used only the semiautomated method. The semiautomated method referred to a fully automated segmentation program customized based on MATLAB and followed manual verification. After highlighting the inner and outer choroidal boundaries through automated segmentation, examiners reviewed these boundaries in each B-scan and conducted manual revisions if segmentation errors occurred. After selecting points where correct boundary was located, the software used a spline fit to blend the corrected region with the rest of the boundary. All measurements were summarized in a 6-mm Early Treatment Diabetic Retinopathy Study grid. Operation time spent to complete retinal and choroidal segmentation on each eye was recorded. Between-examiner agreements, that is, intraclass correlation coefficient and coefficient of reproducibility (CoR), were calculated among four sets of semiautomated measurements, and within-examiner agreements were comparisons between manual and semiautomated results from the same naive examiners. Eyes with thin or thick choroids were also analyzed separately. RESULTS: The between-examiner and within-examiner agreements were excellent with intraclass correlation coefficient of 0.976 or greater. Pairwise within-examiner CoRs ranged from 17.4 to 47.1 µm. Pairwise between-examiner CoRs were between 13.0 and 38.9 µm. Eyes with thin choroid had better agreements than those with thick choroids. On average, naive examiners saved 3 to 5 minutes per eye using the semiautomated method. CONCLUSIONS: With the help of a dedicated software, inexperienced practitioners could obtain choroidal thickness measurements with accuracy similar to experienced practitioners. Processing time with the semiautomated method was also reduced.


Assuntos
Corioide/anatomia & histologia , Adulto , Corioide/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Masculino , Tamanho do Órgão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
7.
Ophthalmic Physiol Opt ; 40(4): 472-481, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32495401

RESUMO

PURPOSE: To measure regional variations in anterior scleral resistance (ASR) using a ballistic rebound tonometer (RBT) and examine whether the variations are significantly affected by ethnicity and refractive error (RE). METHODS: ASR was measured using a RBT (iCare TA01) following calibration against the biomechanical properties of agarose biogels. Eight scleral regions (nasal, temporal, superior, inferior, inferior-nasal, inferior-temporal, superior-nasal and superior-temporal) were measured at locations 4mm from the limbus. Subjects were 130 young adults comprising three ethnic groups whose RE distributions [MSE (D) ± S.D.] incorporated individuals categorised as without-myopia (NM; MSE ≥ -0.50) and with-myopia (WM; MSE < -0.50); British-White (BW): 26 NM + 0.52 ± 1.15D; 22 WM -3.83 ± 2.89D]; British-South-Asian (BSA): [9 NM + 0.49 ± 1.06D; 11 WM -5.07 ± 3.76D; Hong-Kong-Chinese (HKC): [11 NM + 0.39 ± 0.66D; 49 WM -4.46 ± 2.70D]. Biometric data were compiled using cycloplegic open-field autorefraction and the Zeiss IOLMaster. Two- and three-way repeated measures analysis of variances (anovas) tested regional differences for RBT values across both refractive status and ethnicity whilst stepwise forward multiple linear regression was used as an exploratory test. RESULTS: Significant regional variations in ASR were identified for the BW, BSA and HKC (p < 0.001) individuals; superior-temporal region showed the lowest levels of resistance whilst the inferior-nasal region the highest. Compared to the BW and BSA groups, the HKC subjects displayed a significant increase in mean resistance for each respective region (p < 0.001). With the exception of the inferior region, ethnicity was found to be the chief predictor for variation in the scleral RBT values for all other regions. Mean RE group differences were insignificant. CONCLUSIONS: The novel application of RBT to the anterior sclera confirm regional variation in ASR. Greater ASR amongst the HKC group than the BW and BSA individuals suggests that ethnic differences in anterior scleral biomechanics may exist.


Assuntos
Biometria/métodos , Miopia/fisiopatologia , Esclera/fisiopatologia , Tonometria Ocular/métodos , Adulto , Feminino , Humanos , Masculino , Manometria , Miopia/diagnóstico , Esclera/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto Jovem
8.
Ophthalmic Physiol Opt ; 37(1): 42-50, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27873338

RESUMO

PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS: Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed. RESULTS: Corneal tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm-1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.


Assuntos
Comprimento Axial do Olho/fisiopatologia , Córnea/fisiopatologia , Miopia Degenerativa/fisiopatologia , Adulto , Córnea/patologia , Topografia da Córnea , Elasticidade , Feminino , Humanos , Pressão Intraocular , Masculino , Miopia Degenerativa/diagnóstico , Índice de Gravidade de Doença , Adulto Jovem
12.
Optom Vis Sci ; 92(5): 604-14, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25875686

RESUMO

PURPOSE: To characterize and compare the corneal shapes and monochromatic aberrations in Chinese myopic adults with and without astigmatism. METHODS: Forty-six Hong Kong Chinese aged 50 to 70 years with compound against-the-rule myopic astigmatism (n = 18) or simple myopia (n = 28) were recruited. Corneal shapes were measured by a Scheimpflug-based corneal topographer: the semimeridian corneal shape factors at the nasal, temporal, inferior, and superior corneal quadrants measured from the corneal apex to 3 mm midperiphery were analyzed. The ocular aberrations were measured by the COAS (Complete Ophthalmic Analysis System) Shack-Hartmann wavefront aberrometer; the corneal aberrations were computed using the corneal topographic map data measured by the Medmont E300 corneal topographer; and the internal aberrations were calculated from the ocular and corneal aberrations. RESULTS: Compared with simple myopia, myopic astigmatism had more oblate nasal and temporal corneal shapes and showed significantly more negative Y trefoil and more positive vertical coma. The asymmetry in corneal shape along the vertical principal meridian (inferior - superior) was significantly associated with the Y trefoil and vertical coma of the cornea, suggesting that this regional asymmetry in corneal shape may contribute to the ocular aberrations. CONCLUSIONS: The significant relationships found between astigmatism, corneal shapes, and monochromatic aberrations underscore the importance of taking corneal shape into account when correcting the optical defects in myopic Chinese adults with astigmatism.


Assuntos
Astigmatismo/fisiopatologia , Córnea/patologia , Aberrações de Frente de Onda da Córnea/fisiopatologia , Miopia/fisiopatologia , Aberrometria , Idoso , Povo Asiático/etnologia , Astigmatismo/etnologia , China/epidemiologia , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/etnologia
13.
Ophthalmic Physiol Opt ; 35(4): 455-61, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26094834

RESUMO

PURPOSE: The aim of the study was to evaluate the repeatability of a new device for measuring corneal biomechanics. METHODS: Twenty-nine normal subjects aged 20-28 years (23.4 ± 1.7 years) underwent measurements of corneal stiffness and tangent elastic modulus using a novel corneal indentation device. Corneal topography, axial biometry and Goldmann applanation tonometry were also performed during the visit. Subjects returned after about 1 week, at approximately the same time, and with the corneal biomechanics, corneal topography and Goldmann applanation tonometry measured again. Both the intrasession and intersession repeatability was assessed. RESULTS: Both the corneal stiffness and tangent elastic modulus demonstrated good intrasession repeatability (corneal stiffness: coefficient of variation = 7.32%, intraclass correlation coefficient = 0.75; tangent elastic modulus: coefficient of variation = 7.34%, intraclass correlation coefficient = 0.84). The mean modulus after normalised to normal intraocular pressure of 15.5 mmHg was 0.755 ± 0.159 MPa. There was no significant difference between the two visits (paired t-tests: p > 0.05). The repeatability [1.96 times the standard deviation (S.D.) of the intersession difference] of the corneal stiffness and the tangent elastic modulus was 0.0022 N mm(-1) and 0.197 MPa, respectively. CONCLUSION: The corneal indentation device has good intrasession and intersession repeatability. It has good potential to measure corneal biomechanics clinically, even at different corneal regions.


Assuntos
Córnea/fisiologia , Topografia da Córnea/instrumentação , Tonometria Ocular/instrumentação , Adulto , Módulo de Elasticidade/fisiologia , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
14.
Proc Natl Acad Sci U S A ; 109(29): 11717-22, 2012 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-22753465

RESUMO

The Wnt/ß-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Receptores Frizzled/metabolismo , Neoplasias/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Anticorpos Monoclonais/metabolismo , Antineoplásicos/metabolismo , Western Blotting , Células CHO , Cricetinae , Cricetulus , Sinergismo Farmacológico , Vetores Genéticos/genética , Células HEK293 , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Imuno-Histoquímica , Lentivirus , Luciferases , Neoplasias/metabolismo , Biblioteca de Peptídeos , Via de Sinalização Wnt/fisiologia
15.
Gastroenterology ; 144(5): 933-44, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23415803

RESUMO

BACKGROUND & AIMS: Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir. METHODS: We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later. RESULTS: After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval [CI], 3.6%-5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75-0.86), 0.76 (95% CI, 0.70-0.82), and 0.71 (95% CI, 0.62-0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores <5 at baseline, those with CU-HCC scores that either decreased from ≥5 to <5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P < .001, respectively). CONCLUSIONS: The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Medição de Risco/métodos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carcinoma Hepatocelular/etiologia , Intervalos de Confiança , DNA Viral/análise , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Guanina/administração & dosagem , Guanina/efeitos adversos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hong Kong/epidemiologia , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco
16.
Hepatology ; 58(5): 1537-47, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23389810

RESUMO

UNLABELLED: Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 ± 12 years; follow-up, 36 ± 13 months) and 424 treatment-naïve patients (65% men; age, 41 ± 13 years; follow-up, 114 ± 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P = 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P = 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. CONCLUSION: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Adulto , Idoso , Carcinoma Hepatocelular/prevenção & controle , DNA Viral/sangue , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/mortalidade , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
17.
Clin Exp Optom ; 107(2): 213-218, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36975202

RESUMO

CLINICAL RELEVANCE: Change in intraocular pressure during acute ocular compression is related to aqueous humour dynamics. Monitoring intraocular pressure (IOP) change throughout ocular compression has potential to evaluate aqueous outflow facilities. BACKGROUND: Recent studies have monitored lamina cribrosa deformation using optical coherence tomography during ocular compression. IOP was measured only once immediately after ocular compression. This study aimed to evaluate IOP changes during and after ocular compression and compare the differences between low and high myopia. METHODS: Two groups of young, healthy adults were age-matched and underwent ocular compression. IOP was measured at baseline and monitored during a 2-min ocular compression followed by a 10-min recovery phase. Rebound tonometry was used and applied at 30-s intervals. RESULTS: Thirty low and 30 high myopes (60 right eyes) were included in the study. They had similar baseline IOP at 14.9 mmHg. IOP was elevated to 21.7 ± 3.8 mmHg and 22.3 ± 4.2 mmHg for the low and high myopic group, respectively (p = 0.877). Low myopes had faster IOP decay during ocular compression at -3.24 mmHg/min than high myopes at -2.58 mmHg/min (p = 0.0528). The IOP dropped below the baseline level after the release of the compressive force. Low myopes had IOP that returned to baseline levels faster (at 360 s) than high myopes (at 510 s). CONCLUSION: Measuring IOP once immediately after ocular compression could under-estimate the effect of IOP elevation during ocular compression. Further studies are required regarding IOP changes from ocular compression in aqueous humour dynamics.


Assuntos
Pressão Intraocular , Miopia , Adulto , Humanos , Olho , Tonometria Ocular/métodos , Tomografia de Coerência Óptica/métodos
18.
Retin Cases Brief Rep ; 18(1): 138-140, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36007175

RESUMO

PURPOSE: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." METHODS: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. RESULTS: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. CONCLUSION: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Masculino , Humanos , Adulto , Oclusão da Veia Retiniana/induzido quimicamente , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Nitrito de Amila/uso terapêutico , Bevacizumab/uso terapêutico , Edema Macular/tratamento farmacológico , Tomografia de Coerência Óptica , Corpo Vítreo , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêutico , Resultado do Tratamento
19.
Acad Med ; 99(4S Suppl 1): S35-S41, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109661

RESUMO

ABSTRACT: Precision education (PE) leverages longitudinal data and analytics to tailor educational interventions to improve patient, learner, and system-level outcomes. At present, few programs in medical education can accomplish this goal as they must develop new data streams transformed by analytics to drive trainee learning and program improvement. Other professions, such as Major League Baseball (MLB), have already developed extremely sophisticated approaches to gathering large volumes of precise data points to inform assessment of individual performance.In this perspective, the authors argue that medical education-whose entry into precision assessment is fairly nascent-can look to MLB to learn the possibilities and pitfalls of precision assessment strategies. They describe 3 epochs of player assessment in MLB: observation, analytics (sabermetrics), and technology (Statcast). The longest tenured approach, observation, relies on scouting and expert opinion. Sabermetrics brought new approaches to analyzing existing data in a way that better predicted which players would help the team win. Statcast created precise, granular data about highly attributable elements of player performance while helping to account for nonplayer factors that confound assessment such as weather, ballpark dimensions, and the performance of other players. Medical education is progressing through similar epochs marked by workplace-based assessment, learning analytics, and novel measurement technologies. The authors explore how medical education can leverage intersectional concepts of MLB player and medical trainee assessment to inform present and future directions of PE.


Assuntos
Beisebol , Educação Médica , Humanos , Escolaridade , Local de Trabalho
20.
Sci Rep ; 14(1): 6112, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480777

RESUMO

Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm's canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman's test, p < 0.001). There was significant change in SC area (median 10,063.5 µm2 at baseline to median 10,151.0 µm2 after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 µm at baseline to 144.6 ± 25.3 µm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (-2 to -52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 µm vs. 276.5 ± 68.7 µm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 µm vs. 733.5 ± 111.6 µm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = -0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = -0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = -0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman's ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.


Assuntos
Glaucoma , Hipotensão Ocular , Adulto , Humanos , Pressão Intraocular , Canal de Schlemm , Esclera , Tonometria Ocular , Malha Trabecular , Glaucoma/terapia , Tomografia de Coerência Óptica/métodos , Massagem
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