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1.
Med Sci (Paris) ; 36(10): 886-892, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33026331

RESUMO

Age-related macular degeneration (AMD) is a complex, highly heritable, multifactorial disease caused by the interplay of age and genetic and environmental risk factors. No treatment has yet been found to treat the slowly progressing atrophic form of AMD. All forms of AMD are invariably associated with an accumulation of mononuclear phagocytes (MP) in the subretinal space, a family of cells that include inflammatory and resident macrophages. We here present an overview of the inflammatory process occurring in AMD and discuss the origin of MPs and the consequences of their accumulation in the subretinal space. Finally, we will review the role played by the established risk factors for AMD to promote the switch from beneficial inflammation in early stage to a deleterious inflammation in the advanced stage of the disease.


Assuntos
Inflamação/complicações , Degeneração Macular/etiologia , Olho/imunologia , Olho/metabolismo , Olho/patologia , Humanos , Privilégio Imunológico/fisiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Degeneração Macular/epidemiologia , Degeneração Macular/imunologia , Degeneração Macular/metabolismo , Fatores de Risco
2.
Anticancer Res ; 40(11): 6123-6135, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109550

RESUMO

BACKGROUND/AIM: The importance of hadron therapy in the cancer management is growing. We aimed to refine the biological effect detection using a vertebrate model. MATERIALS AND METHODS: Embryos at 24 and 72 h postfertilization were irradiated at the entrance plateau and the mid spread-out Bragg peak of a 150 MeV proton beam and with reference photons. Radiation-induced DNA double-strand breaks (DSB) and histopathological changes of the eye, muscles and brain were evaluated; deterioration of specific organs (eye, yolk sac, body) was measured. RESULTS: More and longer-lasting DSBs occurred in eye and muscle cells due to proton versus photon beams, albeit in different numbers. Edema, necrosis and tissue disorganization, (especially in the eye) were observed. Dose-dependent morphological deteriorations were detected at ≥10 Gy dose levels, with relative biological effectiveness between 0.99±0.07 (length) and 1.12±0.19 (eye). CONCLUSION: Quantitative assessment of radiation induced changes in zebrafish embryos proved to be beneficial for the radiobiological characterization of proton beams.


Assuntos
Fótons , Prótons , Peixe-Zebra/fisiologia , Animais , Encéfalo/efeitos da radiação , Dano ao DNA , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Embrião não Mamífero/efeitos da radiação , Olho/patologia , Olho/efeitos da radiação , Cinética , Tamanho do Órgão/efeitos da radiação , Eficiência Biológica Relativa , Saco Vitelino/patologia , Saco Vitelino/efeitos da radiação , Peixe-Zebra/embriologia
3.
Medicine (Baltimore) ; 99(37): e22171, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925785

RESUMO

The correlations between retinal vessel distribution, anterior chamber depth (ACD) and other myopic eye structural parameters remains elusive. This study aims to investigate retinal vasculature and eye structure correlations in healthy and myopic eyes of Chinese young adults.In this cross-sectional study, 181 eyes (97 adults) were recruited. Macular and peripapillary vasculature was quantified by optical coherence tomography angiography. Correlations between retinal vasculature and eye structure were analyzed using multivariable linear regression.There were significant differences in ACD, spherical equivalent, axial length (AL), superficial macular vascular density (MVD), peripapillary vascular density (PVD) and circumference of foveal avascular zone (FAZ) among emmetropia, low-myopia, moderate-myopia, and high-myopia groups (both P < 0.05). Furthermore, ACD had significant positive correlation with AL and FAZ, but negative correlation with PVD. MVD also had a negative correlation with AL (beta = -0.247, P < .001). In addition, there was a significant negative correlation between circumference of the FAZ and spherical equivalent as well as central subfield thickness (beta = -0.20, P = .005; beta = -0.334, P < .001, respectively).The degree of myopia affected ACD, MVD, PVD, and circumference of the FAZ in eyes of young healthy adults. Meanwhile, ACD has a positive, while retinal vascular system measurements have a negative correlation with increasing severity of myopia.


Assuntos
Olho/irrigação sanguínea , Olho/patologia , Miopia/patologia , Vasos Retinianos/patologia , Adolescente , Adulto , Fatores Etários , Glicemia , Capilares/patologia , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Tomografia de Coerência Óptica , Adulto Jovem
4.
Am J Trop Med Hyg ; 103(4): 1691-1693, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783793

RESUMO

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus endemic throughout Asia. Incidence in non-endemic countries is rare, with an estimate of less than one case per one million travelers. Most human JE infections are asymptomatic or cause a mild, nonspecific febrile illness. Neurological involvement, if present, is usually severe and associated with high mortality or ongoing neurological sequelae in survivors. Ocular manifestations are rare with JE, but uveitis has been described to be associated with other flavivirus infections, including West Nile virus. We report the first probable case of JE chorioretinitis acquired by a 45-year-old Australian traveler to Bali. This case highlights the importance of a detailed ocular examination when there is clinical suspicion of JE.


Assuntos
Coriorretinite/diagnóstico por imagem , Vírus da Encefalite Japonesa (Espécie)/imunologia , Encefalite Japonesa/diagnóstico por imagem , Austrália , Coriorretinite/virologia , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Encefalite Japonesa/patologia , Encefalite Japonesa/virologia , Olho/diagnóstico por imagem , Olho/patologia , Olho/virologia , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Viagem
5.
J Vis Exp ; (161)2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32773758

RESUMO

Spectral-domain optical coherence tomography (SD-OCT) is useful for visualizing retinal and ocular structures in vivo. In research, SD-OCT is a valuable tool to evaluate and characterize changes in a variety of retinal and ocular disease and injury models. In light induced retinal degeneration models, SD-OCT can be used to track thinning of the photoreceptor layer over time. In glaucoma models, SD-OCT can be used to monitor decreased retinal nerve fiber layer and total retinal thickness and to observe optic nerve cupping after inducing ocular hypertension. In diabetic rodents, SD-OCT has helped researchers observe decreased total retinal thickness as well as decreased thickness of specific retinal layers, particularly the retinal nerve fiber layer with disease progression. In mouse models of myopia, SD-OCT can be used to evaluate axial parameters, such as axial length changes. Advantages of SD-OCT include in vivo imaging of ocular structures, the ability to quantitatively track changes in ocular dimensions over time, and its rapid scanning speed and high resolution. Here, we detail the methods of SD-OCT and show examples of its use in our laboratory in models of retinal degeneration, glaucoma, diabetic retinopathy, and myopia. Methods include anesthesia, SD-OCT imaging, and processing of the images for thickness measurements.


Assuntos
Oftalmopatias/diagnóstico por imagem , Olho/diagnóstico por imagem , Olho/patologia , Tomografia de Coerência Óptica , Animais , Comprimento Axial do Olho , Modelos Animais de Doenças , Feminino , Processamento de Imagem Assistida por Computador , Masculino , Camundongos Endogâmicos BALB C , Miopia/diagnóstico por imagem , Miopia/patologia , Células Fotorreceptoras de Vertebrados/patologia , Ratos , Retina/diagnóstico por imagem , Retina/patologia
6.
J Med Internet Res ; 22(8): e20007, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32804086

RESUMO

BACKGROUND: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance. OBJECTIVE: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example. METHODS: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and vision compromise a side effect of hydroxychloroquine therapy? At the time of designing this study, hydroxychloroquine was a leading candidate in the treatment of coronavirus disease (COVID-19). We then leveraged AI to pull and screen articles, automatically extract their results, review the studies, and analyze the data with standard statistical methods. RESULTS: By combining AI with human analysis in our RMA, we generated a meaningful, clinical result in less than 30 minutes. The RMA identified 11 studies considering ocular toxicity as a side effect of hydroxychloroquine and estimated the incidence to be 3.4% (95% CI 1.11%-9.96%). The heterogeneity across individual study findings was high, which should be taken into account in interpretation of the result. CONCLUSIONS: We demonstrate that a novel approach to meta-analysis using AI can generate meaningful clinical insights in a much shorter time period than traditional meta-analysis.


Assuntos
Inteligência Artificial , Infecções por Coronavirus/tratamento farmacológico , Oftalmopatias/etiologia , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Metanálise como Assunto , Pneumonia Viral/tratamento farmacológico , Olho/efeitos dos fármacos , Olho/patologia , Humanos , Pandemias , Fatores de Tempo
7.
PLoS One ; 15(8): e0237403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790713

RESUMO

Genome duplication leads to an emergence of gene paralogs that are essentially free to undergo the process of neofunctionalization, subfunctionalization or degeneration (gene loss). Onecut1 (Oc1) and Onecut2 (Oc2) transcription factors, encoded by paralogous genes in mammals, are expressed in precursors of horizontal cells (HCs), retinal ganglion cells and cone photoreceptors. Previous studies have shown that ablation of either Oc1 or Oc2 gene in the mouse retina results in a decreased number of HCs, while simultaneous deletion of Oc1 and Oc2 leads to a complete loss of HCs. Here we study the genetic redundancy between Oc1 and Oc2 paralogs and focus on how the dose of Onecut transcription factors influences abundance of individual retinal cell types and overall retina physiology. Our data show that reducing the number of functional Oc alleles in the developing retina leads to a gradual decrease in the number of HCs, progressive thinning of the outer plexiform layer and diminished electrophysiology responses. Taken together, these observations indicate that in the context of HC population, the alleles of Oc1/Oc2 paralogous genes are mutually interchangeable, function additively to support proper retinal function and their molecular evolution does not follow one of the typical routes after gene duplication.


Assuntos
Fator 6 Nuclear de Hepatócito/genética , Proteínas de Homeodomínio/genética , Retina/fisiologia , Fatores de Transcrição/genética , Alelos , Células Amácrinas/metabolismo , Células Amácrinas/patologia , Animais , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Olho/crescimento & desenvolvimento , Olho/patologia , Loci Gênicos , Genótipo , Fator 6 Nuclear de Hepatócito/metabolismo , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Transgênicos , Retina/citologia , Retina/patologia , Células Bipolares da Retina/metabolismo , Células Bipolares da Retina/patologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Fatores de Transcrição/metabolismo
8.
PLoS One ; 15(8): e0238122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853278

RESUMO

PURPOSE: Myopia prevalence is influenced by environmental factors including heritability and social disadvantage. The current prevalence of myopia among disadvantaged school children in Australia has not been reported. Therefore, this study analyses refractive data for children from rural and outer suburban areas. METHODS: The records of 4,365 children aged 6-15 visiting a city-based government-school respite care center during the years 2014/2016/2018 were analyzed for right eye non-cycloplegic spherical equivalent refraction (SER). The prevalence of myopia (SER≤-0.50D) was compared with historical data. RESULTS: The prevalence of myopia was 3.5%, 4.4% and 4.3% in 2014, 2016 and 2018, respectively. The prevalence of myopia increased with age (P<0.0001), but was not related to sex or year of testing (all P >0.05). The overall mean SER was 0.89±0.86D, 0.62±0.89D and 0.56±0.95 in 2014, 2016 and 2018, respectively. Mean SER was associated with year of testing, age (all P <0.0001) and sex (P = 0.03). Mean SER decreased slightly from 2014 to 2018 and demonstrated a significant shift towards less hyperopia with increasing age. Mean SER of females was higher than that of males and decreased faster than in males with age (P interaction = 0.03). CONCLUSIONS: Myopia prevalence increased with age. The mean SER decreased slightly from 2014 to 2018. Sex differences in the rate of change with age was observed. Compared with 40 years ago, the prevalence of myopia has doubled, but it remains significantly lower than in school children of a similar age living in established urban areas that are regarded as having a higher socioeconomic status.


Assuntos
Miopia/epidemiologia , Adolescente , Austrália/epidemiologia , Criança , Estudos Transversais , Olho/patologia , Feminino , Humanos , Hiperopia/epidemiologia , Masculino , Prevalência , Erros de Refração/epidemiologia , Instituições Acadêmicas , Testes Visuais/métodos , Populações Vulneráveis
9.
PLoS One ; 15(7): e0235408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649686

RESUMO

The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.


Assuntos
Síndromes do Olho Seco/diagnóstico , Imunoensaio/métodos , Metaloproteinase 9 da Matriz/metabolismo , Síndrome de Sjogren/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/metabolismo , Córnea/patologia , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Olho/metabolismo , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Lágrimas/metabolismo , Tomografia de Coerência Óptica/métodos , Adulto Jovem
10.
DNA Cell Biol ; 39(8): 1449-1457, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32609007

RESUMO

Kearns-Sayre Syndrome (KSS) is a severe mitochondrial disorder involving the central nervous system, eyes, ears, skeletal muscles, and heart. The mitochondrial DNA (mtDNA) rearrangements, especially the deletions, are present in almost all KSS patients and considered as the disease-causing factor. However, the size and position of mtDNA deletions are distinct in different individuals. In this study, we report the case of a pair of Chinese twins with KSS. The twin patients revealed typical KSS clinical symptoms, including heart block, bilateral sensorineural hearing loss, progressive external ophthalmoplegia, exercise intolerance, proximal limb weakness, and endocrine disorders. Using long-range polymerase chain reactions (long-range PCR) and next-generation sequencing (NGS), the genetic features of the twin patients were investigated. A large 6600 bp mtDNA deletion, ranging from position 8702 to 15,302, was detected in both patients. To our knowledge, this kind of mtDNA deletion has never been described previously. Our study enriched the mutation spectrum of KSS and showed that NGS is a powerful tool for detecting mtDNA large variants.


Assuntos
DNA Mitocondrial/genética , Doenças em Gêmeos/genética , Síndrome de Kearns-Sayre/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Sistema Nervoso Central/patologia , Criança , Cromossomos/genética , Doenças em Gêmeos/patologia , Orelha/patologia , Olho/patologia , Deleção de Genes , Predisposição Genética para Doença , Coração/fisiopatologia , Humanos , Síndrome de Kearns-Sayre/patologia , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/patologia , Fenótipo
13.
Arch Biochem Biophys ; 688: 108403, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32418893

RESUMO

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na+/K+-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K+) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K+ flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K+ influx. Moreover, we also noted a decreased expression of Na+/K+-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na+/K+-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.


Assuntos
Olho/metabolismo , Homeostase/fisiologia , Músculo Liso/metabolismo , Miopia/metabolismo , Potássio/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Olho/patologia , Cobaias , Ácido Láctico/metabolismo , Masculino , Músculo Liso/patologia , Miopia/patologia , RNA Mensageiro/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo
14.
Adv Exp Med Biol ; 1244: 295-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301024

RESUMO

Emerging immunotherapy agents, such as immune checkpoint inhibitors, have shown remarkable promise in the treatment of various malignancies. These drugs selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. Due to the novelty of these therapeutic agents, their toxicity profile is less well understood.Meta-analysis results reveal that the overall prevalence of oral mucositis, stomatitis, and xerostomia is lower with checkpoint inhibitors compared to conventional chemotherapy, and head and neck radiation therapy. However, the widespread use of immunotherapy reveals new oral mucosal barrier adverse events, including bullous pemphigoid, mucous membrane pemphigoid, and lichenoid mucositis. Audiovestibular dysfunction can occur from autoimmune-mediated pathways of immunotherapy (adoptive cell) with limited treatment options. Such auditory complications can lead to speech recognition deficits and sensorineural hearing loss. Ocular toxicities are among the most common adverse events resulting from the use of these agents. The majority of ocular immune-related adverse events (irAEs) are mild, low-grade, non-sight threatening, such as blurred vision, conjunctivitis, and ocular surface disease. Serious and sight-threatening events, including corneal perforation, optic neuropathy, and retinal vascular occlusion, can occur but are infrequent. In this chapter, we review the current evidence on the clinical manifestations of oral, audiovestibular, and ocular immune-related adverse events (i.e., irAEs).


Assuntos
Orelha/patologia , Olho/efeitos dos fármacos , Olho/patologia , Imunoterapia/efeitos adversos , Boca/efeitos dos fármacos , Boca/patologia , Neoplasias/terapia , Humanos
17.
Ecotoxicol Environ Saf ; 193: 110371, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32114246

RESUMO

Medroxyprogesterone acetate (MPA) is a widely used synthetic progestin in contraception pills and hormone replacement therapy. However, its effects on eye growth and development and function were largely unknown. In this study, the transcription of genes in the Notch signaling pathway and the visual cycle network were evaluated after chronic MPA exposure at 4.32 (L), 42.0 (M), and 424 (H) ng L-1 for 120 days in zebrafish. Meanwhile, the histology of the eyes was also examined. Transcriptional results showed that MPA at all three concentrations significantly increased the transcription of notch1a, dll4, jag1a, ctbp1 and rbpjb (key genes in the Notch signaling pathway) in the eyes of females. The up-regulation of noth1a, ctbp1 and kat2b was also observed in the eyes of males exposed to MPA at 424 ng L-1. In the visual cycle pathway, MPA increased the transcription of opn1sw1, opn1sw2, arr3a and rpe65a in the eyes of females from the M and H treatments. Histopathological analysis showed that exposure to 42.0 ng L-1 of MPA increased the thicknesses of inner nuclear layer in females and outer segment in males. Moreover, exposure to 424 ng L-1 of MPA increased the lens diameter in females. These results indicated that chronic MPA exposure affected the transcription of genes in the Notch signaling and in the visual cycle pathways, resulting in overgrowth of the eyes and interference of the eye functions. This study suggests that MPA pose a risk to fitness and survival of zebrafish in areas where MPA contamination exists.


Assuntos
Contraceptivos Hormonais/toxicidade , Olho/efeitos dos fármacos , Acetato de Medroxiprogesterona/toxicidade , Animais , Olho/crescimento & desenvolvimento , Olho/patologia , Feminino , Masculino , Receptores Notch/metabolismo , Retina , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
19.
PLoS Biol ; 18(3): e3000632, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163402

RESUMO

Proteins are typically denatured and aggregated by heating at near-boiling temperature. Exceptions to this principle include highly disordered and heat-resistant proteins found in extremophiles, which help these organisms tolerate extreme conditions such as drying, freezing, and high salinity. In contrast, the functions of heat-soluble proteins in non-extremophilic organisms including humans remain largely unexplored. Here, we report that heat-resistant obscure (Hero) proteins, which remain soluble after boiling at 95°C, are widespread in Drosophila and humans. Hero proteins are hydrophilic and highly charged, and function to stabilize various "client" proteins, protecting them from denaturation even under stress conditions such as heat shock, desiccation, and exposure to organic solvents. Hero proteins can also block several different types of pathological protein aggregations in cells and in Drosophila strains that model neurodegenerative diseases. Moreover, Hero proteins can extend life span of Drosophila. Our study reveals that organisms naturally use Hero proteins as molecular shields to stabilize protein functions, highlighting their biotechnological and therapeutic potential.


Assuntos
Proteínas de Drosophila/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas Argonauta/química , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dessecação , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Olho/patologia , Células HEK293 , Temperatura Alta , Humanos , Interações Hidrofóbicas e Hidrofílicas , L-Lactato Desidrogenase/química , L-Lactato Desidrogenase/metabolismo , Longevidade , Masculino , Neurônios Motores/patologia , Neurônios Motores/fisiologia , Estabilidade Proteica , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Solubilidade
20.
PLoS One ; 15(3): e0230305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168355

RESUMO

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.


Assuntos
Neovascularização de Coroide/economia , Histoplasmose/economia , Seguro Saúde/economia , Degeneração Macular/economia , Retinite/economia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Neovascularização de Coroide/complicações , Neovascularização de Coroide/patologia , Neovascularização de Coroide/terapia , Olho/patologia , Oftalmopatias/economia , Oftalmopatias/epidemiologia , Feminino , Pessoal de Saúde , Histoplasmose/complicações , Histoplasmose/patologia , Histoplasmose/terapia , Humanos , Lactente , Recém-Nascido , Revisão da Utilização de Seguros , Degeneração Macular/patologia , Degeneração Macular/terapia , Masculino , Pessoa de Meia-Idade , Oftalmologia/economia , Retinite/complicações , Retinite/patologia , Retinite/terapia , Estados Unidos/epidemiologia , Visão Ocular/fisiologia , Adulto Jovem
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