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1.
J Neurochem ; 122(1): 196-207, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22506991

RESUMEN

Many genes associated with familial Parkinson's disease contribute to mitochondrial morphology and function. Some of these genes, for example, Pink1 and Parkin, are part of a common pathway. The presenilin-associated rhomboid-like (PARL) gene was recently linked to familial Parkinson's disease. The PARL gene product is found in the inner mitochondrial membrane and cleaves the optic atrophy 1 protein, involved in mitochondrial morphology and apoptosis. In Drosophila, the PARL-related rhomboid-7 gene acts upstream of pink1 and parkin. However, such a genetic relationship is still unknown in vertebrates. Here, we show that the zebrafish genome comprises two parl paralogs: parla and parlb. Morpholino-mediated loss of parla and/or parlb function resulted in mild neurodegeneration, as evidenced by a lower density of dopaminergic neurons. Patterning of dopaminergic neurons was also perturbed in the ventral diencephalon. Morphants exhibited extensive cell death throughout the entire body as well as increased larval mortality. The morphant phenotype could be rescued by injection of human PARL mRNA, but not catalytically inactive PARL, suggesting functional conservation between the human and zebrafish proteins. More importantly, the zebrafish pink1 mRNA as well as the human PINK1 mRNA, but not kinase-dead nor Parkinson's disease-linked mutant PINK1 mRNA, also rescued the morphant phenotype, providing evidence that Parl genes may function upstream of Pink1, as part of a conserved pathway in vertebrates.


Asunto(s)
Tipificación del Cuerpo/genética , Neuronas Dopaminérgicas/fisiología , Metaloproteasas/genética , Proteínas Mitocondriales/deficiencia , Proteínas de Pez Cebra/deficiencia , Proteínas de Pez Cebra/genética , Naranja de Acridina , Animales , Animales Modificados Genéticamente , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Clonación Molecular , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Larva/citología , Proteínas Mitocondriales/genética , Morfolinos/farmacología , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , ARN Mensajero/metabolismo , Alineación de Secuencia/métodos , Tirosina 3-Monooxigenasa/metabolismo , Pez Cebra
2.
Am J Hosp Palliat Care ; 36(11): 1020-1025, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30991816

RESUMEN

BACKGROUND: Patients with terminal conditions are often admitted to the emergency department (ED) for acute medical services, but studies have suggested that multiple ED admissions may negatively impact end-of-life (EOL) care. Research have shown that incorporating palliative care (PC) is integral to optimal EOL care, but it is an aspect of medical practice that is often neglected. The current study sought to provide an overview of health outcomes and hospital costs of patients with cancer admitted to The Ottawa Hospital and/or received acute medical services during their final 2 weeks of life. Cost comparisons and estimates were made between hospital and hospice expenditures. METHODS: We conducted a retrospective chart review of palliative patients who died at The Ottawa Hospital in 2012. A total of 130 patients who visited the ED within 2 weeks of death were included in the analyses. RESULTS: In this cohort of patients, 71% of admitted patients did not have advanced care directives and 85% experienced a metastasis, but only 18% had a PC medical doctor. Patients were hospitalized, on average, for 7 days and hospitalization costs exceeded the estimated hospice cost by approximately 2.5 times (Can$1 041 170.00 at Can$8009.00/patient vs Can$401 570.00 at Can$3089.00/patient, respectively). CONCLUSION: Our study highlighted the importance of PC integration in high-risk patients, such as those in oncology. Patients in our sample had minimal PC involvement, low advanced care directives, and accrued high costs. Based on our analyses, we concluded that these patients would have likely benefited more from hospice care rather than hospitalization.


Asunto(s)
Cuidados Críticos/economía , Cuidados Paliativos al Final de la Vida/economía , Enfermería de Cuidados Paliativos al Final de la Vida/economía , Mortalidad Hospitalaria , Neoplasias/enfermería , Enfermería Oncológica/economía , Cuidado Terminal/economía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Cuidados Críticos/estadística & datos numéricos , Femenino , Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Enfermería de Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Enfermería Oncológica/estadística & datos numéricos , Ontario , Estudios Retrospectivos , Cuidado Terminal/estadística & datos numéricos
3.
Disabil Rehabil Assist Technol ; 13(6): 504-516, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28766367

RESUMEN

PURPOSE: Nature of being accessible to all categories of users is one of the primary factors for enabling the wider reach of the resources published through World Wide Web. The accessibility of websites has been analyzed through W3C guidelines with the help of various tools. This paper presents a multi-tool accessibility assessment of government department websites belonging to the Indian state of Jammu and Kashmir. A comparative analysis of six accessibility tools is also presented with 14 different parameters. MATERIALS AND METHODS: The accessibility analysis tools used in this study for analysis are aChecker, Cynthia Says, Tenon, wave, Mauve, and Hera. These tools provide us the results of selected websites accessibility status on Web Content Accessibility Guidelines (WCAG) 1.0 and 2.0. RESULTS: It was found that there are variations in accessibility analysis results when using different accessibility metrics to measure the accessibility of websites. In addition to this, we have identified the guidelines which have frequently been violated. It was observed that there is a need for incorporating the accessibility component features among the selected websites. This paper presents a set of suggestions to improve the accessibility status of these sites so that the information and services provided by these sites shall reach a wider spectrum of audience without any barrier. Implications for rehabilitation The following points indicates that this case study of JKGAD websites comes under Rehabilitation focused on Visually Impaired users. Due to the universal nature of web, it should be accessible to all according to WCAG guidelines framed by World Wide Web Consortium. In this paper we have identified multiple accessibility barriers for persons with visual impairment while browsing the Jammu and Kashmir Government websites. Multi-tool analysis has been done to pin-point the potential barriers for persons with visually Impaired. Usability analysis has been performed to check whether these websites are suitable for persons with visual impairment. We provide some valuable suggestions which can be followed by developers and designers to minimize these potential accessibility barriers.Based on aforementioned key points, this article helps the persons with disability especially Visually Impaired Users to access the web resources better with the implementation of identified suggestions.


Asunto(s)
Programas de Gobierno/organización & administración , Internet/normas , Trastornos de la Visión/rehabilitación , Personas con Daño Visual/rehabilitación , Programas de Gobierno/normas , Guías como Asunto , Humanos , India
4.
Can J Cardiol ; 34(9): 1158-1164, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30170671

RESUMEN

BACKGROUND: Low-risk syncope accounts for a large proportion of hospital admissions; however, inpatient investigations are often not necessary and are rarely diagnostic. Reducing the number of low-risk syncope admissions can likely lower health care resource consumption and overall expenditure. Application of syncope guidelines by physicians in the emergency department provides a standardized approach that may potentially reduce admissions and lead to health care resource utilization savings. METHODS: A retrospective chart review of 1229 syncope presentations was conducted at 2 major academic centres spanning 1 year. Three major society guidelines and position statements were applied to determine the effect on admission rates. RESULTS: A total of 1031 true syncope charts were included in the analysis; 407 (39%) were admitted and 624 (61%) were discharged by the treating physician (MD). There was a significant difference in the mean [standard deviation] age (75 [14] vs 55 [22]) and baseline cardiovascular disease, including congestive heart failure 51/407 (13%) vs 28/624 (5%), coronary artery disease 125/407 (31%) vs 91/624 (15%), and structural heart disease 36/407 (9%) vs 26/624 (4%), between admitted and not admitted patients, respectively (P < 0.01). All guidelines warranted more low-risk admissions when compared with 19% by the MD: Canadian Cardiovascular Society 34% (P < 0.01), American College of Emergency Physicians 22% (P = 0.03), and European Society of Cardiology 26% (P < 0.01). CONCLUSION: In conclusion, application of the current syncope guidelines to an emergency department population is unlikely to reduce low-risk hospital admissions.


Asunto(s)
Servicio de Urgencia en Hospital , Admisión del Paciente/estadística & datos numéricos , Manejo de Atención al Paciente , Guías de Práctica Clínica como Asunto , Síncope , Adulto , Anciano , Canadá , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Adhesión a Directriz/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/normas , Estudios Retrospectivos , Medición de Riesgo , Síncope/diagnóstico , Síncope/etiología , Síncope/terapia
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