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1.
Sci Rep ; 14(1): 6112, 2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480777

RESUMEN

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.


Asunto(s)
Glaucoma , Hipotensión Ocular , Adulto , Humanos , Presión Intraocular , Canal de Schlemm , Esclerótica , Tonometría Ocular , Malla Trabecular , Glaucoma/terapia , Tomografía de Coherencia Óptica/métodos , Masaje
2.
Sci Rep ; 14(1): 5979, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472220

RESUMEN

Quantitative assessment of retinal microvasculature in optical coherence tomography angiography (OCTA) images is important for studying, diagnosing, monitoring, and guiding the treatment of ocular and systemic diseases. However, the OCTA user community lacks universal and transparent image analysis tools that can be applied to images from a range of OCTA instruments and provide reliable and consistent microvascular metrics from diverse datasets. We present a retinal extension to the OCTA Vascular Analyser (OCTAVA) that addresses the challenges of providing robust, easy-to-use, and transparent analysis of retinal OCTA images. OCTAVA is a user-friendly, open-source toolbox that can analyse retinal OCTA images from various instruments. The toolbox delivers seven microvascular metrics for the whole image or subregions and six metrics characterising the foveal avascular zone. We validate OCTAVA using images collected by four commercial OCTA instruments demonstrating robust performance across datasets from different instruments acquired at different sites from different study cohorts. We show that OCTAVA delivers values for retinal microvascular metrics comparable to the literature and reduces their variation between studies compared to their commercial equivalents. By making OCTAVA publicly available, we aim to expand standardised research and thereby improve the reproducibility of quantitative analysis of retinal microvascular imaging. Such improvements will help to better identify more reliable and sensitive biomarkers of ocular and systemic diseases.


Asunto(s)
Mácula Lútea , Vasos Retinianos , Reproducibilidad de los Resultados , Angiografía con Fluoresceína/métodos , Microvasos , Tomografía de Coherencia Óptica/métodos
3.
Sci Adv ; 10(11): eadh9547, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489372

RESUMEN

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (CKLF) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4+ cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4+ T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4+ suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.


Asunto(s)
Quimiocinas , Proteínas con Dominio MARVEL , Proteína Proto-Oncogénica N-Myc , Neuroblastoma , Humanos , Línea Celular Tumoral , Quimiocinas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas con Dominio MARVEL/metabolismo , Proteína Proto-Oncogénica N-Myc/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patología , Neuroblastoma/terapia , Microambiente Tumoral
4.
Clin Exp Optom ; 107(2): 213-218, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36975202

RESUMEN

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.


Asunto(s)
Presión Intraocular , Miopía , Adulto , Humanos , Ojo , Tonometría Ocular/métodos , Tomografía de Coherencia Óptica/métodos
5.
Acad Med ; 99(4S Suppl 1): S35-S41, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38109661

RESUMEN

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.


Asunto(s)
Béisbol , Educación Médica , Humanos , Escolaridad , Lugar de Trabajo
6.
Retin Cases Brief Rep ; 18(1): 138-140, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36007175

RESUMEN

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.


Asunto(s)
Edema Macular , Oclusión de la Vena Retiniana , Masculino , Humanos , Adulto , Oclusión de la Vena Retiniana/inducido químicamente , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Nitrito de Amila/uso terapéutico , Bevacizumab/uso terapéutico , Edema Macular/tratamiento farmacológico , Tomografía de Coherencia Óptica , Cuerpo Vítreo , Inyecciones Intravítreas , Inhibidores de la Angiogénesis/uso terapéutico , Resultado del Tratamiento
7.
Lancet Public Health ; 8(9): e691-e700, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37633678

RESUMEN

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival. FINDINGS: Of 42 087 patients with NSCLC in the COS-ILCCO database, 21 893 (52·0%) of whom were male and 20 194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37 613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10 841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions. INTERPRETATION: In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time. FUNDING: The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Femenino , Masculino , Estudios Retrospectivos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Estudios de Cohortes , Fumar/epidemiología
8.
Sci Rep ; 13(1): 12714, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37543611

RESUMEN

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.


Asunto(s)
Miopía , Disco Óptico , Adulto , Humanos , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Tomografía de Coherencia Óptica/métodos , Reproducibilidad de los Resultados , Presión Intraocular , Células Ganglionares de la Retina/patología , Miopía/diagnóstico por imagen , Miopía/patología , Atrofia/patología
9.
Front Public Health ; 11: 1178769, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457285

RESUMEN

Objective: Electronic devices have become an indispensable part of our daily lives. The frequency and duration of device use in children and adolescents have increased drastically over the years and the study of its negative musculoskeletal, visual and psychosocial health impacts is necessary. Materials and methods: This cross-sectional study aimed to evaluate the associations between electronic device use and the prevalence and severity of musculoskeletal symptoms, visual symptoms, psychosocial health, and quality of life in children and adolescents studying at primary and secondary schools. Data were collected through confidential online and paper-and-pencil questionnaires. Primary 4-5 and Secondary 1-4 students were recruited from 3 schools in Hong Kong. Demographics, frequency and duration of electronic device use, frequencies of musculoskeletal symptoms, visual symptoms, psychosocial health, and quality of life outcomes were measured. Results: 1,058 children and adolescents aged 9-17 years participated. Sixty-one percent and 78% of all students spent more than 2 h per day using electronic devices during school days and weekend/holidays, respectively. Extended electronic device use was associated with increased prevalence and severity of musculoskeletal symptoms (ρ's = 0.28-0.33, P's < 0.001), visual symptoms (ρ's = 0.33-0.35, P's < 0.001), and poorer device use-related psychosocial health (ρ's = 0.38-0.47, P's < 0.001). Secondary school students reported greater device use and severity of symptoms than primary school students. Conclusion: Excessive electronic device use was associated with increased prevalence and severity of physical and psychosocial symptoms, and such use is more prevalent in adolescents when compared to the children. The findings have important health implications for children and adolescents, suggesting that early intervention is needed to reduce the risk of developing device use-related disorders.


Asunto(s)
Calidad de Vida , Estudiantes , Humanos , Niño , Adolescente , Estudios Transversales , Encuestas y Cuestionarios , Electrónica
10.
J Glaucoma ; 32(7): 585-592, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37055937

RESUMEN

PRCIS: Lamina cribrosa (LC) thinning (thickness of ≤128.00 µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. PURPOSE: The purpose of this study was to analyze the factors associated with LC thickness in highly myopic eyes with and without open angle glaucoma. METHODS: In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open angle glaucoma) were examined, and the LC center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. RESULTS: LC were thinner in highly myopic open angle glaucoma compared with high myopia alone (107.76±9.86 vs. 137.07±18.51 µm, P <0.001), which was associated with deep layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open angle glaucoma from the LC thickness was 0.964, which was statistically higher ( P <0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A LC thickness cutoff value of 128 µm provided 100% sensitivity for detecting open angle glaucoma with 84% specificity. CONCLUSIONS: Highly myopic eyes with open angle glaucoma appear to have a thinner LC, which was associated with elevated intraocular pressure and deep layer microvasculature dropout. LC thinning (≤128.00 µm) helps distinguish open angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.


Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Miopía , Disco Óptico , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/complicaciones , Disco Óptico/irrigación sanguínea , Presión Intraocular , Glaucoma/complicaciones , Miopía/complicaciones , Miopía/diagnóstico , Tomografía de Coherencia Óptica/métodos
11.
JCO Clin Cancer Inform ; 7: e2200153, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36930839

RESUMEN

PURPOSE: Lung cancer screening programs generate a high volume of low-dose computed tomography (LDCT) reports that contain valuable information, typically in a free-text format. High-performance named-entity recognition (NER) models can extract relevant information from these reports automatically for inter-radiologist quality control. METHODS: Using LDCT report data from a longitudinal lung cancer screening program (8,305 reports; 3,124 participants; 2006-2019), we trained a rule-based model and two bidirectional long short-term memory (Bi-LSTM) NER neural network models to detect clinically relevant information from LDCT reports. Model performance was tested using F1 scores and compared with a published open-source radiology NER model (Stanza) in an independent evaluation set of 150 reports. The top performing model was applied to a data set of 6,948 reports for an inter-radiologist quality control assessment. RESULTS: The best performing model, a Bi-LSTM NER recurrent neural network model, had an overall F1 score of 0.950, which outperformed Stanza (F1 score = 0.872) and a rule-based NER model (F1 score = 0.809). Recall (sensitivity) for the best Bi-LSTM model ranged from 0.916 to 0.991 for different entity types; precision (positive predictive value) ranged from 0.892 to 0.997. Test performance remained stable across time periods. There was an average of a 2.86-fold difference in the number of identified entities between the most and the least detailed radiologists. CONCLUSION: We built an open-source Bi-LSTM NER model that outperformed other open-source or rule-based radiology NER models. This model can efficiently extract clinically relevant information from lung cancer screening computerized tomography reports with high accuracy, enabling efficient audit and feedback to improve quality of patient care.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares , Humanos , Retroalimentación , Mejoramiento de la Calidad , Neoplasias Pulmonares/diagnóstico por imagen , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X , Radiólogos
12.
Cancer ; 129(6): 867-877, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36653915

RESUMEN

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.


Asunto(s)
Neoplasias de Cabeza y Cuello , Cese del Hábito de Fumar , Productos de Tabaco , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Fumar/efectos adversos , Fumar/epidemiología
13.
Health Promot Pract ; 24(2): 201-206, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35094594

RESUMEN

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.


Asunto(s)
COVID-19 , Equidad en Salud , Humanos , COVID-19/epidemiología , Pandemias/prevención & control , Salud Pública , Ontario/epidemiología
14.
J Biol Chem ; 299(2): 102806, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36529289

RESUMEN

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.


Asunto(s)
Chaperonas Moleculares , Fragmentos de Péptidos , Priones , Proteína FUS de Unión a ARN , beta Carioferinas , Humanos , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/terapia , beta Carioferinas/química , beta Carioferinas/genética , beta Carioferinas/metabolismo , Línea Celular , Dependovirus/metabolismo , Demencia Frontotemporal/metabolismo , Demencia Frontotemporal/terapia , Técnicas In Vitro , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Priones/química , Priones/metabolismo , Deficiencias en la Proteostasis/metabolismo , Deficiencias en la Proteostasis/terapia , Proteína FUS de Unión a ARN/química , Proteína FUS de Unión a ARN/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Unión Proteica
15.
BMJ Open ; 12(9): e062264, 2022 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-36153026

RESUMEN

INTRODUCTION: Unwarranted variation in patient care among physicians is associated with negative patient outcomes and increased healthcare costs. Care variation likely also exists for resident physicians. Despite the global movement towards outcomes-based and competency-based medical education, current assessment strategies in residency do not routinely incorporate clinical outcomes. The widespread use of electronic health records (EHRs) may enable the implementation of in-training assessments that incorporate clinical care and patient outcomes. METHODS AND ANALYSIS: The General Medicine Inpatient Initiative Medical Education Database (GEMINI MedED) is a retrospective cohort study of senior residents (postgraduate year 2/3) enrolled in the University of Toronto Internal Medicine (IM) programme between 1 April 2010 and 31 December 2020. This study focuses on senior IM residents and patients they admit overnight to four academic hospitals. Senior IM residents are responsible for overseeing all overnight admissions; thus, care processes and outcomes for these clinical encounters can be at least partially attributed to the care they provide. Call schedules from each hospital, which list the date, location and senior resident on-call, will be used to link senior residents to EHR data of patients admitted during their on-call shifts. Patient data will be derived from the GEMINI database, which contains administrative (eg, demographic and disposition) and clinical data (eg, laboratory and radiological investigation results) for patients admitted to IM at the four academic hospitals. Overall, this study will examine three domains of resident practice: (1) case-mix variation across residents, hospitals and academic year, (2) resident-sensitive quality measures (EHR-derived metrics that are partially attributable to resident care) and (3) variations in patient outcomes across residents and factors that contribute to such variation. ETHICS AND DISSEMINATION: GEMINI MedED was approved by the University of Toronto Ethics Board (RIS#39339). Results from this study will be presented in academic conferences and peer-reviewed journals.


Asunto(s)
Pacientes Internos , Internado y Residencia , Competencia Clínica , Humanos , Medicina Interna , Estudios Retrospectivos
16.
J. optom. (Internet) ; 15(3): 1-9, Jul-Sep.2022. tab
Artículo en Inglés | IBECS | ID: ibc-204705

RESUMEN

Purpose: To monitor effect of caffeine on vasculature of the inner retina of high myopesMethods: This was a crossover, self‐control, randomized trial. Healthy young high myopes were recruited to take 200 mg of caffeine capsule and placebo capsule, randomly assigned in two visits separated by at least one week. Superficial retinal vasculature in terms of vessel length density (VD) and perfusion area density (PD) was captured and monitored using a spectral domain optical coherence tomography angiography (OCTA) machine. After baseline measurements, blood pressure (BP), intraocular pressure (IOP), and subfoveal choroidal thickness (ChT) were also monitored at 30‐min intervals till 3 h.Results: Eighteen subjects (6 male, 24.3 ± 3.1 years) completed the study. After taking the caffeine capsule, there was a significant increase in BP (p < 0.01), and reduction in ChT (p < 0.01), with no change in IOP (p = 0.36). VD demonstrated a trend of reduction at the central 1‐mm circle, and 1‐3 mm annulus (p < 0.01) following the ETDRS grid. Reduction trend of PD appeared at the central 1‐mm circle, 1‐3 mm annulus, and the entire 3‐mm circle (p < 0.01). Compared with baseline, VD and PD reductions were significant 180 min after taking the caffeine capsule at the central 1‐mm circle, but the reduction was small (VD: by 1mm-1; PD: by 1%). Changes in other regions were not significant.Conclusions: The current study found significant reduction in VD and PD after taking 200 mg of caffeine capsule. Such a small amount of alteration may be clinically irrelevant. (AU)


Asunto(s)
Humanos , Masculino , Cafeína/uso terapéutico , Cafeína , Miopía , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Proyectos Piloto , Vasos Retinianos/diagnóstico por imagen
18.
J Optom ; 15(3): 210-218, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35637106

RESUMEN

PURPOSE: To monitor effect of caffeine on vasculature of the inner retina of high myopes METHODS: This was a crossover, self-control, randomized trial. Healthy young high myopes were recruited to take 200 mg of caffeine capsule and placebo capsule, randomly assigned in two visits separated by at least one week. Superficial retinal vasculature in terms of vessel length density (VD) and perfusion area density (PD) was captured and monitored using a spectral domain optical coherence tomography angiography (OCTA) machine. After baseline measurements, blood pressure (BP), intraocular pressure (IOP), and subfoveal choroidal thickness (ChT) were also monitored at 30-min intervals till 3 h. RESULTS: Eighteen subjects (6 male, 24.3 ± 3.1 years) completed the study. After taking the caffeine capsule, there was a significant increase in BP (p < 0.01), and reduction in ChT (p < 0.01), with no change in IOP (p = 0.36). VD demonstrated a trend of reduction at the central 1-mm circle, and 1-3 mm annulus (p < 0.01) following the ETDRS grid. Reduction trend of PD appeared at the central 1-mm circle, 1-3 mm annulus, and the entire 3-mm circle (p < 0.01). Compared with baseline, VD and PD reductions were significant 180 min after taking the caffeine capsule at the central 1-mm circle, but the reduction was small (VD: by 1mm-1; PD: by 1%). Changes in other regions were not significant. CONCLUSIONS: The current study found significant reduction in VD and PD after taking 200 mg of caffeine capsule. Such a small amount of alteration may be clinically irrelevant.


Asunto(s)
Miopía , Tomografía de Coherencia Óptica , Cafeína/farmacología , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Proyectos Piloto , Vasos Retinianos/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos
19.
Sci Rep ; 12(1): 7104, 2022 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-35501327

RESUMEN

Due to excessive elongation of the eyeball, myopia-related vascular abnormalities are frequently observed in the central retinal artery (CRA) and its intraretinal branches. In addition to inconsistency in previously reported findings, hemodynamic (reduced flow velocity, increased vascular resistance) and morphological changes (narrower vessel diameter) were usually studied separately. This cross-sectional study evaluated the hemodynamic and morphological characteristics concurrently in a large sample of healthy myopes, by using the color Doppler ultrasound and adaptive optics retinal camera. Results showed that the retrobulbar segment of CRA had a tendency of slightly reduced flow velocity in eyeballs with longer axial length, but the correlation was not significant after adjusting for the multiple correlations. Vascular resistance was not affected by the axial elongation. With respect to the intraretinal branches, no significant changes in longer eyes of total diameter or lumen diameter were observed, while both the wall thickness and the wall cross-sectional area were significantly increased, but only a marginally increase in the wall to lumen ratio was found with increasing axial length. This implies some potential small artery remodeling in the intraretinal CRA branches. Overall, blood supply of the inner retina in healthy young myopes is likely to be maintained. Additionally, morphological parameters of vascular microstructure could be potential biomarkers to monitor myopia progression and understand myopia-related vascular abnormalities in future studies.


Asunto(s)
Miopía , Arteria Retiniana , Estudios Transversales , Ojo/irrigación sanguínea , Ojo/diagnóstico por imagen , Hemodinámica , Humanos , Miopía/diagnóstico por imagen , Arteria Retiniana/diagnóstico por imagen
20.
Clin Exp Optom ; 105(3): 247-262, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34343434

RESUMEN

The high prevalence of myopia has become a global concern, especially in East and Southeast Asia. Alarmingly, the prevalence of high myopia is increasing. Mechanical stretching caused by excessive eyeball elongation leads to various anatomical changes in the fundus. This stretching force may also lead to the development of vascular abnormalities, which tend to be subtle and easily overlooked. A healthy ocular vasculature is a prerequisite of adequate oxygen supply for normal retinal functions. This review summarises previous findings on structural and haemodynamic aspects of myopia-related vascular changes.


Asunto(s)
Miopía , Tomografía de Coherencia Óptica , Fondo de Ojo , Hemodinámica , Humanos
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