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1.
Adv Exp Med Biol ; 801: 471-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24664733

RESUMO

The first autosomal dominant mutation identified to cause retinitis pigmentosa in the North American population was the substitution of proline to histidine at position 23 of the rhodopsin gene (P23H RHO). Many biochemical studies have demonstrated that P23H mutation induces rhodopsin (RHO) misfolding leading to endoplasmic reticulum stress. Herein, we review current thinking of this topic.


Assuntos
Deficiências na Proteostase/genética , Deficiências na Proteostase/terapia , Retinose Pigmentar/genética , Retinose Pigmentar/terapia , Rodopsina/genética , Animais , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/genética , Genes Dominantes , Humanos
2.
Proc Natl Acad Sci U S A ; 106(42): 17817-22, 2009 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-19822744

RESUMO

Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.


Assuntos
Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Sistemas de Liberação de Medicamentos , Oligopeptídeos/administração & dosagem , Animais , Calpaína/antagonistas & inibidores , Claudina-5 , Inibidores de Cisteína Proteinase/administração & dosagem , Modelos Animais de Doenças , Eletrorretinografia , Guanosina Trifosfato/administração & dosagem , Guanosina Trifosfato/metabolismo , Humanos , IMP Desidrogenase/deficiência , IMP Desidrogenase/genética , Imageamento por Ressonância Magnética , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interferência de RNA , RNA Interferente Pequeno/genética , Retina/efeitos dos fármacos , Retina/metabolismo , Retinose Pigmentar/tratamento farmacológico , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo
3.
Nurse Educ Today ; 111: 105307, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35217457

RESUMO

BACKGROUND: The COVID-19 pandemic has caused extraordinary disruptions to education systems globally, forcing a rapid switch from conventional to online education. Although some qualitative studies have been carried out exploring the online education experiences of nursing students and faculty members during the COVID-19 pandemic, to our knowledge, no study has used the Photovoice approach. OBJECTIVES: To explore the experiences of nursing students and faculty members as related to online education during the COVID-19 pandemic. DESIGN: A descriptive qualitative design using Photovoice was adopted. SETTING: The study took place across five countries and one city in Southeast Asia (Indonesia, Malaysia, the Philippines, Thailand, Vietnam, and Hong Kong). PARTICIPANTS: Fifty-two nursing students and twenty-eight nursing faculty members who participated in online education during the COVID-19 pandemic. METHODS: Each participant submitted one photo substantiated with written reflections. Data were analysed using thematic analysis. Ethical approval was obtained from institution-specific ethics boards. RESULTS: Three themes and eleven sub-themes emerged from the data. The three main themes were: 1) Psychological roadblocks to online education; 2) Developing resilience despite adversities; and 3) Online education: What worked and what did not. CONCLUSION: Through Photovoice, the reflections revealed that nursing students and faculty members were generally overwhelmed with the online education experience. At the same time, participants were satisfied with the flexibility and convenience, opportunities for professional and personal development and safety afforded by online education. However, concerns over academic integrity, practical skills and clinical competencies, engagement and participation, the duality of technology and social isolation out-shadowed the advantages. It is worthwhile to explore the concerns raised to enhance online education across the nursing curriculum.


Assuntos
COVID-19 , Educação a Distância , Estudantes de Enfermagem , Docentes de Enfermagem , Humanos , Pandemias , Estudantes de Enfermagem/psicologia
4.
Nurse Educ Today ; 110: 105277, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35101809

RESUMO

BACKGROUND: The COVID-19 pandemic has disrupted the lives of many. Particularly, nursing students experience greater stress as their normal curriculum is interrupted and some of them face the risk of being infected as frontline workers. Nursing faculty members may face similar struggles, in addition to developing teaching materials for online learning. Thus, it is important to examine the faculty members' and students' views on their ability to adapt during the pandemic to obtain a holistic view of how learning and training has been affected. DESIGN: The descriptive cross-sectional quantitative design was used. SETTINGS: Data were collected from Southeast and East Asian Nursing Education and Research Network (SEANERN) affiliated nursing institutions from January 2021 to August 2021. PARTICIPANTS: A total of 1897 nursing students and 395 faculty members from SEANERN-affiliated nursing institutions in Cambodia, Hong Kong, Indonesia, Japan, Laos, Malaysia, Philippines, Singapore, Thailand and Vietnam were recruited for this study. METHODS: Quantitative surveys were used to explore the satisfaction levels in education modalities, confidence levels, psychosocial well-being, sense of coherence and stress levels of nursing students and faculty members during the COVID-19 pandemic. RESULTS: Participants were mostly satisfied with the new education modalities, although most students felt that their education was compromised. Both groups showed positive levels of psychosocial well-being, despite scoring low to medium on the sense of coherence scale and experiencing great stress. The participants' sense of coherence was positively correlated with their psychosocial well-being and negatively correlated with stress levels. CONCLUSIONS: While the COVID-19 pandemic had negatively impacted the lives of nursing students and faculty members, most of them had a healthy level of psychosocial well-being. Having a strong sense of coherence was associated with better psychosocial health and lower stress levels. As such, it may be helpful to develop interventions aimed at improving the sense of coherence of nursing students and staff to help them manage stressors better.


Assuntos
COVID-19 , Educação em Enfermagem , Senso de Coerência , Estudantes de Enfermagem , COVID-19/epidemiologia , Estudos Transversais , Docentes de Enfermagem , Humanos , Pandemias , Estudantes de Enfermagem/psicologia , Universidades
5.
J Adv Res ; 10: 9-13, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30046471

RESUMO

We have developed a general method for reverse aromatic Finkelstein reactions. Good reaction yields were obtained when aryl iodides or aryl bromides were treated with copper halide salts as promoters in a 1-butyl-3-methylimidazolium bromide ([BMIM]Br) ionic liquid (IL) solvent at 140 °C for 8 h. Preliminary investigation supported that the copper salts were also the halide sources in halogen exchange reactions. The optimized conditions are applicable to a variety of substrates and have excellent functional group tolerance. Additionally, the [BMIM]Br solvent showed good stability for at least 10 consecutive runs. Results indicated that the [BMIM]Br solvent was recyclable for reverse aromatic Finkelstein reactions.

7.
Eur J Hum Genet ; 20(1): 64-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21863053

RESUMO

Retinitis pigmentosa (RP) is a degenerative retinal disease involving progressive loss of rod and cone photoreceptor function. It represents the most common form of registered blindness among the working aged populations of developed countries. Given the immense genetic heterogeneity associated with this disease, parameters influencing cone photoreceptor survival (preservation of daytime vision) that are independent of primary mutations are exceedingly important to identify from a therapeutic standpoint. Here we identify C1q, the primary component of the classical complement pathway, as a cone photoreceptor neuronal survival factor.


Assuntos
Complemento C1q/metabolismo , Retina/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Retinose Pigmentar/patologia , Animais , Sobrevivência Celular , Via Clássica do Complemento , Modelos Animais de Doenças , Eletrorretinografia , Genótipo , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Receptores de Complemento/metabolismo , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Retinose Pigmentar/metabolismo
8.
Nat Commun ; 3: 849, 2012 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-22617289

RESUMO

Traumatic brain injury is the leading cause of death in children and young adults globally. Malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RNA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology.


Assuntos
Edema Encefálico/etiologia , Edema Encefálico/terapia , Lesões Encefálicas/complicações , Claudinas/metabolismo , Cognição/fisiologia , Animais , Barreira Hematoencefálica/metabolismo , Edema Encefálico/diagnóstico por imagem , Lesões Encefálicas/diagnóstico por imagem , Criança , Claudina-5 , Claudinas/genética , Humanos , Pressão Intracraniana/fisiologia , Masculino , Camundongos , Interferência de RNA , Tomografia Computadorizada por Raios X
9.
EMBO Mol Med ; 3(4): 235-45, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21374818

RESUMO

We describe a procedure for controlled, periodic, reversible modulation of selected regions of the blood-brain barrier (BBB) or the inner-blood-retina barrier (iBRB) based on incorporation into an AAV-2/9 vector of a doxycycline-inducible gene encoding shRNA targeting claudin-5, one of 30 or so proteins constituting the BBB and iBRB. The vector may be introduced stereotaxically into pre-selected regions of the brain or into the retina, rendering these regions permeable to low-molecular weight compounds up to approximately 1 kDa for the period of time during which the inducing agent, doxycycline, is administered in drinking water, but excluding potentially toxic higher molecular weight materials. We report on the use of barrier modulation in tandem with systemic drug therapy to prevent retinal degeneration and to suppress laser-induced choroidal neovascularization (CNV), the latter being the hallmark pathology associated with the exudative, or wet, form of age-related macular degeneration (AMD). These observations constitute the basis of a minimally invasive systemic therapeutic modality for retinal diseases, including retinitis pigmentosa and AMD, where, in early stage disease, the iBRB is intact and impervious to systemically administered drugs.


Assuntos
Barreira Hematorretiniana/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Terapia Genética , Degeneração Macular/terapia , Animais , Barreira Hematorretiniana/inervação , Barreira Hematorretiniana/metabolismo , Linhagem Celular , Claudina-5 , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Degeneração Macular/genética , Degeneração Macular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peso Molecular , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico
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