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1.
Indian J Ophthalmol ; 72(5): 681-686, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153980

RESUMO

PURPOSE: To report clinical profiles of multiple sclerosis (MS)-associated uveitis in seven cases from a single tertiary eye care center in South India. METHODS: Retrospective case series 2013-2023. RESULTS: Seven cases of MS-associated uveitis were retrieved from our databases. There were five females and two males. The diagnosis of MS was made by the neurologist in all cases. Bilaterality was seen in all cases. Intermediate uveitis was the most common presentation (five cases). It was associated with peripheral retinal vasculitis (two cases) and disc pallor (two cases). Fuchs heterochromic iridocyclitis (one case) and incomplete Vogt-Koyanagi-Harada (VKH)-like presentation with a peripapillary choroidal neovascular membrane (one case) were the other presentations. In the case with incomplete VKH-like presentation, whole genome sequencing revealed a heterozygous non-synonymous variation (c.1228C>T) in exon 10 of TNFRSF1A, suggestive of susceptibility to multiple sclerosis 5 due to mutation in the TNFRS1A gene on chromosome 12p13.31. All cases received systemic steroids. Azathioprine (three cases) and rituximab (three cases) were the commonly used immunomodulatory drugs. The visual outcome was good in all cases at the last follow-up. CONCLUSION: MS-associated uveitis is underreported in India. This series highlights the clinical profile of MS-associated uveitis in India.

2.
J Clin Med ; 12(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37685625

RESUMO

The aims of this study were to assess whether completion of the emergency department (ED) Big 6 interventions (provision of pain relief, screening for delirium, early warning score (EWS) system, full blood investigation and electrocardiogram, intravenous fluids therapy, and pressure area care) in those presenting with an acute hip fracture were associated with mortality risk and length of acute hospital stay. A retrospective cohort study was undertaken. All patients aged ≥50 years that were admitted with a hip fracture via the ED at a single centre during a 42-month period were included. A total of 3613 patients (mean age 80.9; 71% female) were included. The mean follow up was 607 (range 240 to 1542) days. A total of 1180 (32.7%) patients had all six components completed. Pain relief (90.8%) was the most frequently completed component and pressure area assessment (57.6%) was the least. Completion of each of the individual Big 6 components, except for pressure areas assessment, were associated with a significantly (p ≤ 0.041) lower mortality risk at the 90-days, one-year and final follow-up. The completion of all components of the Big 6 was associated with a significantly (2.4 hours, p = 0.002) shorter time to theatre. Increasing number of Big 6 components completed were independently associated with a lower mortality risk: when all six were completed, the hazard ratio was 0.64 (95% CI 0.52 to 0.78, p < 0.001). Completion of an increasing number of Big 6 components was independently associated with shorter length of hospital stay and completion of all six was associated with a 2.3 (95% CI 0.9 to 3.8)-day shorter acute stay. The findings provide an evidence base to support the ongoing use of the Big 6 in the ED.

3.
Eur Radiol ; 33(9): 6582-6591, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37042979

RESUMO

OBJECTIVES: While fully supervised learning can yield high-performing segmentation models, the effort required to manually segment large training sets limits practical utility. We investigate whether data mined line annotations can facilitate brain MRI tumor segmentation model development without requiring manually segmented training data. METHODS: In this retrospective study, a tumor detection model trained using clinical line annotations mined from PACS was leveraged with unsupervised segmentation to generate pseudo-masks of enhancing tumors on T1-weighted post-contrast images (9911 image slices; 3449 adult patients). Baseline segmentation models were trained and employed within a semi-supervised learning (SSL) framework to refine the pseudo-masks. Following each self-refinement cycle, a new model was trained and tested on a held-out set of 319 manually segmented image slices (93 adult patients), with the SSL cycles continuing until Dice score coefficient (DSC) peaked. DSCs were compared using bootstrap resampling. Utilizing the best-performing models, two inference methods were compared: (1) conventional full-image segmentation, and (2) a hybrid method augmenting full-image segmentation with detection plus image patch segmentation. RESULTS: Baseline segmentation models achieved DSC of 0.768 (U-Net), 0.831 (Mask R-CNN), and 0.838 (HRNet), improving with self-refinement to 0.798, 0.871, and 0.873 (each p < 0.001), respectively. Hybrid inference outperformed full image segmentation alone: DSC 0.884 (Mask R-CNN) vs. 0.873 (HRNet), p < 0.001. CONCLUSIONS: Line annotations mined from PACS can be harnessed within an automated pipeline to produce accurate brain MRI tumor segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities. KEY POINTS: • A brain MRI tumor detection model trained using clinical line measurement annotations mined from PACS was leveraged to automatically generate tumor segmentation pseudo-masks. • An iterative self-refinement process automatically improved pseudo-mask quality, with the best-performing segmentation pipeline achieving a Dice score of 0.884 on a held-out test set. • Tumor line measurement annotations generated in routine clinical radiology practice can be harnessed to develop high-performing segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities.


Assuntos
Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Adulto , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem
4.
Hum Vaccin Immunother ; 18(7): 2150030, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36476258

RESUMO

We evaluated safety, reactogenicity, and immunogenicity when the WHO-prequalified single-dose Typhoid Vi-polysaccharide conjugate vaccine, Typbar-TCV®, was administered concomitantly with measles (MV) or measles-mumps-rubella (MMR) vaccines in 8- or 9-month-old children. We enrolled 493 children who were randomized 2:1:1:1 to four groups to receive either TCV (0.5 mL intramuscularly) and MV (0.5 ml subcutaneously) concomitantly at 9 months of age (Group 1) with two subgroups given TCV booster 28 days (Group 1A) or 180 days (Group 1B) later, or MV on Day 0 and TCV on Day 28 (Group 2); or TCV at 8 months of age and MV 28 days later (Group 3), or MV only at 9 months of age (Group 4). All children received MMR at 15 months of age. We observed no statistically significant differences between group rates of solicited or unsolicited adverse events assessed throughout the study. Seroconversion rates for measles, mumps, and rubella antibodies were unaffected by concomitant administration with TCV, being similar in Groups 1, 2, and 3 and comparable to Group 4 (Control). IgG anti-Vi antibody titers were similar in all groups after primary Typbar-TCV® vaccination and were not increased by a second dose 28 days later. A small response to a booster dose of Typbar-TCV® given at 180 days did not achieve the high titers observed after the first dose, suggesting that booster vaccination may be more effective after a longer interval than 6 months. Typbar-TCV® can be safely co-administered with measles and MMR vaccines in children aged ≥9 months.Clinical trial registration number: CTRI/2014/04/004532.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola , Sarampo , Caxumba , Febre Tifoide , Criança , Humanos , Lactente , Anticorpos Antivirais , Sarampo/prevenção & controle , Caxumba/prevenção & controle , Toxoide Tetânico/efeitos adversos , Febre Tifoide/prevenção & controle , Vacinas Combinadas , Vacinas Conjugadas/efeitos adversos
5.
Radiol Artif Intell ; 3(6): e210013, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34870216

RESUMO

Integration of artificial intelligence (AI) applications within clinical workflows is an important step for leveraging developed AI algorithms. In this report, generalizable components for deploying AI systems into clinical practice are described that were implemented in a clinical pilot study using lymphoscintigraphy examinations as a prospective use case (July 1, 2019-October 31, 2020). Deployment of the AI algorithm consisted of seven software components, as follows: (a) image delivery, (b) quality control, (c) a results database, (d) results processing, (e) results presentation and delivery, (f) error correction, and (g) a dashboard for performance monitoring. A total of 14 users used the system (faculty radiologists and trainees) to assess the degree of satisfaction with the components and overall workflow. Analyses included the assessment of the number of examinations processed, error rates, and corrections. The AI system processed 1748 lymphoscintigraphy examinations. The system enabled radiologists to correct 146 AI results, generating real-time corrections to the radiology report. All AI results and corrections were successfully stored in a database for downstream use by the various integration components. A dashboard allowed monitoring of the AI system performance in real time. All 14 survey respondents "somewhat agreed" or "strongly agreed" that the AI system was well integrated into the clinical workflow. In all, a framework of processes and components for integrating AI algorithms into clinical workflows was developed. The implementation described could be helpful for assessing and monitoring AI performance in clinical practice. Keywords: PACS, Computer Applications-General (Informatics), Diagnosis © RSNA, 2021.

6.
Radiographics ; 41(5): 1420-1426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34388050

RESUMO

Natural language processing (NLP) is a methodology designed to extract concepts and meaning from human-generated unstructured (free-form) text. It is intended to be implemented by using computer algorithms so that it can be run on a corpus of documents quickly and reliably. To enable machine learning (ML) techniques in NLP, free-form text must be converted to a numerical representation. After several stages of preprocessing including tokenization, removal of stop words, token normalization, and creation of a master dictionary, the bag-of-words (BOW) technique can be used to represent each remaining word as a feature of the document. The preprocessing steps simplify the documents but also potentially degrade meaning. The values of the features in BOW can be modified by using techniques such as term count, term frequency, and term frequency-inverse document frequency. Experience and experimentation will guide decisions on which specific techniques will optimize ML performance. These and other NLP techniques are being applied in radiology. Radiologists' understanding of the strengths and limitations of these techniques will help in communication with data scientists and in implementation for specific tasks. Online supplemental material is available for this article. ©RSNA, 2021.


Assuntos
Processamento de Linguagem Natural , Radiologia , Algoritmos , Humanos , Aprendizado de Máquina , Radiologistas
7.
Comput Methods Programs Biomed ; 209: 106347, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34399152

RESUMO

BACKGROUND AND OBJECTIVES: Overexpression of prosurvival Bcl-2 family members make tumor cells resistant to conventional cancer therapeutic agents. It is commonly observed feature in many different types of human tumors. Hence, small-molecules as Bcl-2 inhibitors may have a promising therapeutic potential for the treatment of human cancer. The given study focusses on development of novel and small Bcl-2 inhibitors using ligand-based drug design approach. METHODS: Ligand based pharmacophore was generated using the PHASE tool of Schrödinger and screened ZINC database through ZINCPharmer webserver to identify compounds with similar features. Compounds having good fitness score were selected for molecular docking and binding interactions were compared with drugs in market as well as trials. QSAR model was generated using advanced AutoQSAR tool and validated for prediction of unknown compounds. QSAR prediction of in silico active identified three potential compounds and were subjected to investigate stability by molecular dynamics simulations and MM-PBSA binding energy calculations. RESULTS: Study identified three in silico potential molecules with good stability and binding affinity. Further substructure search and pIC50 value prediction has identified six more molecules. Total nine molecules have demonstrated good drug likeness features. CONCLUSION: Final oral rat LD50 calculation of nine molecules has identified three hit molecules i.e., ZINC76760927, ZINC76768675 and ZINC52767796 for further in vitro and in vivo testing as safe and potential Bcl-2 inhibitors.


Assuntos
Neoplasias , Relação Quantitativa Estrutura-Atividade , Animais , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Ratos
8.
Br J Anaesth ; 126(1): 77-86, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32703548

RESUMO

BACKGROUND: The optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. METHODS: We conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70-90 g L-1) or liberal (haemoglobin, 90-110 g L-1) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. RESULTS: We enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L-1 or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L-1; 95% confidence interval [CI], 1.6-12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L-1; 95% CI, 1.7-9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8-72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was -16.7% (95% CI, -41.3 to 7.8; P=0.18). CONCLUSION: A clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible. CLINICAL TRIAL REGISTRATION: NCT03407573.


Assuntos
Transfusão de Sangue/métodos , Fraturas do Colo Femoral/cirurgia , Infarto do Miocárdio/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Prospectivos
9.
Graefes Arch Clin Exp Ophthalmol ; 259(5): 1333-1342, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33119803

RESUMO

INTRODUCTION: Rubella is an important infectious, vaccine-preventable etiology of congenital defects. The aim of the study was to develop a prediction nomogram to assess the probability of an infant being at risk for congenital rubella based on demographics and ophthalmological findings. METHODS: This was a cross-sectional sentinel surveillance study conducted at 5 centers spanning pan-India and involved 1134 infants. The diagnosis of rubella was made using standard guidelines. For the construction of the prediction model, laboratory-confirmed cases were grouped as "at-risk" (AR) infants and the discarded cases into "not at risk" (NAR) infants. Univariate analysis (p value cut-off < 0.05) followed by multivariate binary logistic regression model development was performed. RESULTS: The average (median) age of the suspected CRS infants was 3 (IQR 1-6) months, and the average (mean) age of their mothers was 25.8 ± 4.1 years. Out of the total infants, 81 (7.3%) died, 975 (88%) were alive, and 55 (5.0%) were lost to follow-up. The final model showed that the odds of cataract, retinopathy, glaucoma, microcornea, and age of the infant at presentation were 3.1 (2.2-4.3), 4.9(2.3-10.4), 2.7(1.1-5.9), 2.3(1.1-4.7), and 1.1 (1-1.1), respectively, for the AR infant as compared to NAR infant. AUC of final model was 0.68 (95% CI Delong, 0.64-0.72). Bootstrapping for calibration of the model showed satisfactory results. Nomogram, along with a web version, was developed. CONCLUSION: The developed nomogram would have a wide community-based utilization and will help in prioritizing attention to high-risk children, thereby avoiding loss to follow-up.


Assuntos
Rubéola (Sarampo Alemão) , Vigilância de Evento Sentinela , Anticorpos Antivirais , Criança , Estudos Transversais , Humanos , Lactente , Nomogramas , Probabilidade , Rubéola (Sarampo Alemão)/diagnóstico , Rubéola (Sarampo Alemão)/epidemiologia
10.
Indian J Ophthalmol ; 68(9): 2007-2009, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32823460

RESUMO

In this report we describe nongranulomatous uveitis followed by bilateral retinal vasculitis and much later by the loss of accommodation as initial presentations of demyelinating disease in a 42-year-old female with no other neurologic manifestations. The absence of demyelinating plaques in the initial magneric resonance imaging (MRI) (orbit and cranium) and its occurrence 2 years later, have been described as "lesions appearing with time". Extensive laboratory investigations ruled out infections, systemic vasculitis, and connective tissue disorders. Due to the presence of oligoclonal bands in both cerebrospinal fluid (CSF) and serum, absence of antiaquaporin-4, antimyelin-oligodendrocyte glycoprotein immunoglobulin G (IgG) antibodies, and negative vasculitis profile, the exact cause of demyelination (multiple sclerosis/vasculitis related) could not be ascertained. She has currently received 2 cycles of rituximab and at the last follow-up did not show any recurrences.


Assuntos
Esclerose Múltipla , Vasculite Retiniana , Uveíte , Adulto , Feminino , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/etiologia , Rituximab
11.
OMICS ; 24(6): 379-389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32496972

RESUMO

Mapping the normal eye proteome in healthy persons is essential to unravel the molecular basis of diseases impacting visual health. The vitreous occupies a large portion of the human eye between the lens and the retina and plays a significant role in vitreoretinal diseases as well as maintaining clarity in the visual field, providing nutrition to the lens, and protecting the eye from mechanical shocks. It comprises four distinct anatomical regions, namely the vitreous core, vitreous cortex, vitreous base, and anterior hyaloid. Among these, the vitreous is attached to other substructures in the eye by the vitreous base, which is its strongest point of attachment. Alterations in vitreous substructures have been reported in several vitreoretinal disorders, including vitreomacular traction, vitreoretinopathies, and age-related macular degeneration. There has been limited knowledge on proteomics variations at a resolution of vitreous substructures, including the functionally and pathophysiologically significant vitreous base. We report here new findings on the proteome map of the vitreous base in normal healthy tissue. We employed a global, unbiased proteomic profiling approach resulting in the identification of 6511 proteins. Of these, 302 proteins were involved in metabolic processes essential for energy utilization. Moreover, we identified several structural and nutrient transport proteins. Notably, the identified proteome repertoire indicates that the vitreous base might possess additional physiological functions and may not be a passive structure. This study constitutes the most extensive catalog of vitreous base proteins to our knowledge and offers novel insights as a baseline for future studies on the pathobiology of various eye diseases. These data also invite us to consider a potentially more active functional role for the vitreous base in eye physiology and visual health.


Assuntos
Proteínas do Olho/metabolismo , Proteoma , Proteômica , Corpo Vítreo/metabolismo , Biologia Computacional/métodos , Análise de Dados , Ontologia Genética , Humanos , Proteômica/métodos , Transdução de Sinais , Espectrometria de Massas em Tandem
12.
OMICS ; 24(3): 129-139, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125911

RESUMO

Success rates of corneal transplantation are particularly high owing to its unique, innate immune privilege derived from a phenomenon known as Anterior Chamber-Associated Immune Deviation (ACAID). Of note, cornea is a transparent, avascular structure that acts as a barrier along with sclera to protect the eye and contributes to optical power. Molecular and systems biology mechanisms underlying ACAID and the immunologically unique and privileged status of cornea are not well known. We report here a global unbiased proteomic profiling of the human cornea and the identification of 4824 proteins, the largest catalog of human corneal proteins identified to date. Moreover, signaling pathway analysis revealed enrichment of spliceosome, phagosome, lysosome, and focal adhesion pathways, thereby demonstrating the protective functions of corneal proteins. We observed an enrichment of neutrophil-mediated immune response processes in the cornea as well as proteins belonging to the complement and ER-Phagosome pathways that are suggestive of active immune and inflammatory surveillance response. This study provides a key expression map of the corneal proteome repertoire that should enable future translational medicine studies on the pathological conditions of the cornea and the mechanisms by which cornea immunology are governed. Molecular mechanisms of corneal immune privilege have broad relevance to understand and anticipate graft rejection in the field of organ transplantation.


Assuntos
Câmara Anterior/imunologia , Córnea/imunologia , Proteínas do Olho/genética , Redes Reguladoras de Genes/imunologia , Privilégio Imunológico , Proteínas do Olho/classificação , Proteínas do Olho/imunologia , Adesões Focais/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Lisossomos/imunologia , Neutrófilos/imunologia , Fagossomos/imunologia , Proteômica/métodos , Transdução de Sinais , Spliceossomos/imunologia
13.
Indian J Ophthalmol ; 68(Suppl 1): S74-S77, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31937736

RESUMO

The Indian health infrastructure is struggling to handle the burgeoning number of people with diabetes. Managing the complications of diabetes in an organized manner through the government health programs is still a distant reality. Here, we describe a program aimed at addressing the problem of diabetic retinopathy in rural areas of Tumkur district in Karnataka. By amalgamating telescreening and our own novel distributive care model, we were able to screen 85% of the registered diabetics in the Government noncommunicable disease clinics and treat 95% of those needing laser therapy. We also describe the importance of using electronic medical records in public health programs which not only increase the efficiency in screening for disease but help in increasing uptake of treatment by tracking defaulters.


Assuntos
Retinopatia Diabética/terapia , Programas de Rastreamento/métodos , População Rural , Retinopatia Diabética/epidemiologia , Gerenciamento Clínico , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino
14.
Indian J Ophthalmol ; 68(1): 100-105, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31856481

RESUMO

Purpose: The aim of this study was to determine the seroprevalence of Lymes disease in a population at risk in south India. Methods: Prospective ongoing study and included screening of forest workers and staff of Nagarahole and Bandipur forest ranges in South India for Lymes disease. Screening included a detailed questionnaire for Lymes disease, complete ocular and systemic examination by an ophthalmologist and infectious disease specialist and blood collection. ELISA for IgM and IgG antibodies for Borrelia burgdorferi were performed on the collected sera samples. Western blot confirmation was done on the seropositive samples. Ticks were also collected from these forest areas for future studies to detect if they harbor B. burgdorferi. Results: Seroprevalence of 19.9% was noted by ELISA. Western blot confirmation was seen in 15.6% of the seropositive samples. There was significant correlation between seropositivity and exposure to tick bites (P = 0.023). Conclusion: There is a high seroprevalence of infection with B. burgdorferi in the forest areas of Nagarahole and Bandipur ranges in south India.


Assuntos
Anticorpos Antibacterianos/análise , Borrelia burgdorferi/imunologia , Florestas , Doença de Lyme/imunologia , Adolescente , Adulto , Idoso , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia/epidemiologia , Doença de Lyme/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Soroepidemiológicos , Adulto Jovem
15.
Indian J Ophthalmol ; 68(1): 244-246, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31856540

RESUMO

A 43-year-old immunocompetent male presented with focal macular retinitis with overlying vitritis in the right eye. His BCVA was counting fingers close to face. OCT showed increased intraretinal thickness at the area of retinitis with adjacent hypo reflectivity of the choroid. Serology was positive for IgM and IgG antibodies for toxoplasma. He received oral clindamycin 300 mg 4 times/day for 8 weeks. At 6 weeks, his BCVA was CF 2 metres. Fundus showed complete resolution of retinitis with formation of near, full thickness macular hole with intact overlying ILM. A small hyper reflective scar was seen at the base of the macular hole.


Assuntos
Infecções Oculares Parasitárias/complicações , Macula Lutea/patologia , Perfurações Retinianas/etiologia , Retinite/complicações , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/complicações , Vitrectomia/métodos , Doença Aguda , Adulto , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Humanos , Masculino , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Retinite/diagnóstico , Retinite/parasitologia , Tomografia de Coerência Óptica , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologia
16.
OMICS ; 23(2): 98-110, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30767726

RESUMO

Eye disorders and resulting visual loss are major public health problems affecting millions of people worldwide. In this context, the sclera is an opaque, thick outer coat covering more than 80% of the eye, and essential in maintaining the shape of the eye and protecting the intraocular contents against infection and the external environment. Despite efforts undertaken to decipher the scleral proteome, the functional and structural picture of the sclera still remain elusive. Recently, proteomics has arisen as a powerful tool that enables identification of proteins playing a critical role in health and disease. Therefore, we carried out an in-depth proteomic analysis of the human scleral tissue using a high-resolution Orbitrap Fusion Tribrid mass spectrometer. We identified 4493 proteins using SequestHT and Mascot as search algorithms in Proteome Discoverer 2.1. Importantly, the proteins, including radixin, synaptopodin, paladin, netrin 1, and kelch-like family member 41, were identified for the first time in human sclera. Gene ontology analysis unveiled that the majority of proteins were localized to the cytoplasm and involved in cell communication and metabolism. In sum, this study offers the largest catalog of proteins identified in sclera with the aim of facilitating their contribution to diagnostics and therapeutics innovation in visual health and autoimmune disorders. This study also provides a valuable baseline for future investigations so as to map the dynamic changes that occur in sclera in various pathological conditions.


Assuntos
Proteoma/metabolismo , Proteômica/métodos , Esclera/metabolismo , Biologia Computacional , Humanos , Espectrometria de Massas em Tandem
17.
Indian J Ophthalmol ; 66(12): 1877-1879, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30451212
19.
OMICS ; 22(10): 642-652, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30346883

RESUMO

Ophthalmology and visual health are new frontiers for postgenomic research and technologies such as proteomics. In this context, the optic nerve and retina extend as the outgrowth of the brain, wherein the latter receives the optical input and the former relays the information for processing. While efforts to understand the optic nerve proteome have been made earlier, there exists a lacuna in its biochemical composition and molecular functions. We report, in this study, a high-resolution mass spectrometry-based approach using an Orbitrap Fusion Tribrid mass spectrometer to elucidate the human optic nerve proteomic profile. Raw spectra were searched against NCBI Human RefSeq 75 database using SEQUEST HT and MASCOT algorithms. We identified nearly 35,000 peptides in human optic nerve samples, corresponding to 5682 proteins, of which 3222 proteins are being reported for the first time. Label-free quantification using spectral abundance pointed out to neuronal structural proteins such as myelin basic protein, glial fibrillary acidic protein, and proteolipid protein 1 as the most abundant proteins. We also identified several neurotransmitter receptors and postsynaptic density synaptosomal scaffold proteins. Pathway analysis revealed that a majority of the proteins are structural proteins and have catalytic and binding activity. This study is one of the largest proteomic profiles of the human optic nerve and offers the research community an initial baseline optic nerve proteome for further studies. This will also help understand the protein dynamics of the human optic nerve under normal conditions.


Assuntos
Nervo Óptico/metabolismo , Proteoma , Biologia Computacional , Humanos , Espectrometria de Massas , Proteínas/química , Proteínas/metabolismo
20.
OMICS ; 22(8): 565-574, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30106352

RESUMO

Next-generation sequencing approaches have revolutionized genomic medicine and enabled rapid diagnosis for several diseases. These approaches are widely used for pathogen detection in several infectious diseases. Lyme disease is a tick-borne infectious disease, which affects multiple organs. The causative organism is a spirochete, Borrelia burgdorferi, which is transmitted by ticks. Lyme disease can be treated easily if detected early, but its diagnosis is often delayed or is incorrect leading to a chronic debilitating condition. Current confirmatory diagnostic tests for Lyme disease rely on detection of antigens derived from B. burgdorferi, which are prone to both false positives and false negatives. Instead of focusing only on the human host for the diagnosis of Lyme disease, one could also attempt to identify the vector (tick) and the causative organism carried by the tick. Since all ticks do not transmit Lyme disease, it can be informative to accurately identify the tick from the site of bite, which is often observed by the patient and discarded. However, identifying ticks based on morphology alone requires a trained operator and can still be incorrect. Thus, we decided to take a molecular approach by sequencing DNA and RNA from a tick collected from an individual bitten by the tick. Using next-generation sequencing, we confirmed the identity of the tick as a dog tick, Dermacentor variabilis, and did not identify any pathogenic bacterial sequences, including Borrelia species. Despite the limited availability of nucleotide sequences for many types of ticks, our approach correctly identified the tick species. This proof-of-principle study demonstrates the potential of next-generation sequencing in the diagnosis of tick-borne infections, which can also be extended to other zoonotic diseases.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doença de Lyme/microbiologia , Doença de Lyme/transmissão , Carrapatos/microbiologia , Animais , Borrelia burgdorferi/patogenicidade , Humanos
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