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1.
Neuropsychology ; 38(5): 465-474, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38780595

ABSTRACT

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is often shown to cause episodic memory deficits. Here, we investigated whether such memory deficits are differentially expressed according to the emotional valence of stimuli and whether they are similarly reproduced in both individuals with sporadic ALS (sALS) and familial Type 8 ALS (ALS8). METHOD: Twenty individuals with sALS, 18 individuals with ALS8, and 19 healthy controls were recruited for the study. After a neuropsychological and psychopathological assessment, all participants responded to a recognition memory test wherein images varying in terms of valence were initially shown. After a short interval, the images were shown again intermixed with new images, and the participants' task was to indicate whether each image was "old" or "new" and to estimate the confidence in their responses. RESULTS: Both the sALS and the ALS8 groups showed significantly lower recognition of positive relative to negative valence images (d = 0.92 and d = 0.74, respectively), an effect that was completely absent for healthy controls (d = 0.17). These effects were qualified by a significant interaction involving the factors of valence and group (ηp² = 0.12). CONCLUSIONS: The current findings demonstrate that sALS and ALS8 are associated with decreased recognition of emotional information, an effect that is nonetheless restricted to positive valence stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Amyotrophic Lateral Sclerosis , Emotions , Recognition, Psychology , Humans , Amyotrophic Lateral Sclerosis/psychology , Amyotrophic Lateral Sclerosis/physiopathology , Male , Female , Middle Aged , Emotions/physiology , Aged , Recognition, Psychology/physiology , Memory Disorders/etiology , Memory Disorders/diagnosis , Adult , Memory, Episodic , Neuropsychological Tests
2.
J Glaucoma ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38595198

ABSTRACT

PRECIS: Using OCT, eyes with advanced glaucoma were found to have a wide range of patterns of damage that were consistent with the natural history of progression based upon a model of macular progression. PURPOSE: To understand the patterns of preserved retinal ganglion cells in eyes with advanced glaucoma using OCT and a model of progression of the central macula. METHODS: OCT GCL thickness was measured in 94 eyes with advanced glaucoma, defined as glaucomatous eyes with a 24-2 MD (mean deviation) worse than -12 dB. A commercial report supplied the GCL thickness in 6 sectors of the thick, donut-shaped GCL region around the fovea. For each eye, the 6 sectors were coded as green (within normal limits, WNL), yellow (≤5th, ≥1st percentile), or red (<1st percentile). RESULTS: In all 94 eyes, one or more of the 6 sectors of the donut were abnormal (red or yellow), while all 6 sectors were red in 52 (55%) of the eyes. On the other hand, 33 eyes had one or more sectors WNL (green). While the pattern of donut damage varied widely across these 33 eyes, 61 of the 66 hemiretinas were consistent with a temporal-to-nasal progression of damage within each hemiretina as predicted by our model. CONCLUSION: All eyes with advanced glaucoma had damage to the critically important central, donut-shaped GCL region. This region showed a wide range of patterns of damage, but these patterns were consistent with the natural history of progression based upon a model of macular progression. These results have implications for the clinical identification of macular progression, as well as for inclusion criteria for clinical trials seeking to preserve central macular function.

3.
Transl Vis Sci Technol ; 13(1): 4, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38190190

ABSTRACT

Purpose: We evaluated the ability of an optical coherence tomography (OCT)-based reading center for glaucoma (ORG) to detect established glaucoma using OCT alone. Methods: This study included eyes from 70 consecutive patients with established glaucoma (i.e. moderate or severe glaucoma according to the International Classification of Diseases [ICD]-10 guidelines) and 20 consecutive healthy subjects, who had no evidence of glaucomatous optic neuropathy (GON) or visual field (VF) loss in either eye. Using a standardized ORG quality assessment, 33 eyes were excluded due to media opacity (12), poor image quality (13), or epiretinal membrane (8). Of the remaining 147 eyes, 86 had established glaucoma and 36 were from healthy controls (total n = 122). Based on the OCT report alone and applying a previously described evaluation method, the presence of GON in each eye was determined by two masked ORG graders. The main outcome measures were sensitivity and specificity for detection of eyes with established glaucoma. Results: Of the 86 eyes with established glaucoma (average mean deviation [MD] = -10.9 ± 7.7 dB, range = -0.5 to -31.5 dB), only one eye (MD = -0.46) was missed (sensitivity = 98.8%). However, the other eye of this patient was correctly classified as GON. Therefore, at a patient level, sensitivity was 100%. None of the 36 healthy eyes was classified as GON by the ORG (specificity = 100%). Conclusions: An OCT-based reading center is able to identify eyes with established glaucoma using OCT alone with high sensitivity and specificity. Translational Relevance: Our study validates the use of a systematic OCT-based approach for glaucoma detection in a real-world setting.


Subject(s)
Glaucoma , Optic Nerve Diseases , Humans , Eye , Glaucoma/diagnosis , Tomography, Optical Coherence
4.
Invest Ophthalmol Vis Sci ; 64(15): 8, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38060217

ABSTRACT

The central macula contains a thick donut shaped region of the ganglion cell layer (GCL) that surrounds the fovea. This region, which is about 12 degrees (3.5 mm) in diameter, is essential for everyday functions such as driving, reading, and face recognition. Here, we describe a model of progression of glaucomatous damage to this GCL donut. This model is based upon assumptions supported by the literature, and it predicts the patterns of glaucomatous damage to the GCL donut, as seen with optical coherence tomography (OCT). After describing the assumptions and predictions of this model, we test the model against data from our laboratory, as well as from the literature. Finally, three uses of the model are illustrated. One, it provides an aid to help clinicians focus on the essential central macula and to alert them to look for other, non-glaucomatous causes, when the GCL damage does not fit the pattern predicted by the model. Second, the patterns of progression predicted by the model suggest alternative end points for clinical trials. Finally, the model provides a heuristic for future research concerning the anatomic basis of glaucomatous damage.


Subject(s)
Glaucoma , Macula Lutea , Humans , Retinal Ganglion Cells , Nerve Fibers , Glaucoma/diagnosis , Retina , Tomography, Optical Coherence/methods , Intraocular Pressure
5.
Optom Vis Sci ; 100(8): 499-506, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37499165

ABSTRACT

SIGNIFICANCE: The reports from optical coherence tomography (OCT) instruments depend on a reference database (RDB) of healthy eyes. Although these RDBs tend to be relatively small, they are time consuming and expensive to obtain. A larger RDB should improve our ability to screen for diseases such as glaucoma. PURPOSE: To explore the feasibility of developing a large RDB from OCT scans obtained by optometrists as part of their pre-test gathering of information, we tested the hypothesis that these scans are of sufficient quality for an RDB and contain a relatively low base rate of glaucoma and other pathologies (OPs). METHODS: Optical coherence tomography widefield (12 × 9 mm) scans from 400 eyes of 400 patients were randomly selected from a data set of more than 49,000 scans obtained from four optometry sites. Based on a commercial OCT report and a previously validated reading center method, two OCT graders categorized eyes as unacceptable to use for RDB, healthy (H), optic neuropathy consistent with glaucoma (ON-G), glaucoma suspect, or OPs. RESULTS: Overall, 29 (7.25%) of the eyes were graded unacceptable. Of the remaining 371 eyes, 352 (94.9%) were graded H. Although, for one site, 7.4% of the eligible eyes were graded ON-G, the average for the other three sites was 1.4%. Adjustments of the reading center criteria resulted in exclusion of more than half of these ON-G and OP eyes. CONCLUSIONS: The OCT scans obtained from optometry practices as part of their pre-test regimen are of sufficient quality for an RDB and contain a relatively low base rate of glaucoma and OPs. With the suggested exclusion criteria, the scans from optometry practices that are primarily involved in refraction and medical screening services should yield a large, real-world RDB with improved specificity and a base rate of glaucoma and/or OPs comparable with existing RDB.


Subject(s)
Glaucoma , Optometry , Humans , Tomography, Optical Coherence/methods , Visual Field Tests/methods , Visual Fields , Glaucoma/diagnosis , Retinal Ganglion Cells/pathology , Intraocular Pressure
6.
Neuropsychology ; 36(1): 86-93, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34726462

ABSTRACT

OBJECTIVE: Prior studies have shown that individuals with Parkinson's disease (PD) exhibit deficits in the processing of emotional information. Here, we investigated whether such deficits caused by PD reduce the mnemonic benefits typically produced by emotion in healthy individuals. METHOD: Thirty individuals with PD and 30 healthy individuals, matched for sex, age, and education, were recruited for the study. To assess their memory for emotional information, we asked them to observe a series of negative, positive, and neutral images distributed in three consecutive blocks. After a short interval, all observed images were presented again intermixed with new images, and the participants were asked to judge whether each image was "old" or "new" (i.e., recognition test), and to indicate the block in which each image was studied (i.e., source memory test). In addition, to characterize the sample, all participants responded to a series of neuropsychological and psychopathological tests. RESULTS: As expected, individuals with PD exhibited diminished overall recognition and source memory scores relative to healthy controls (ηp² = 0.16 and 0.14, respectively). More importantly, while healthy controls showed greater recognition accuracy for negative versus neutral images (d = 0.65), this advantage was absent for PD participants (d < 0.18), a null effect corroborated by Bayesian analysis (BF01 = 3.34). CONCLUSION: The current findings suggest that individuals with PD lack the mnemonic advantage for negative pictures shown by healthy individuals, a deficit that may result from their difficulties in the processing of emotional information. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Memory, Episodic , Parkinson Disease , Bayes Theorem , Emotions , Humans , Neuropsychological Tests , Parkinson Disease/diagnostic imaging , Recognition, Psychology
7.
Cells ; 10(7)2021 06 30.
Article in English | MEDLINE | ID: mdl-34209333

ABSTRACT

Pulmonary hypertension (PH) is a cardiovascular disease caused by extensive vascular remodeling in the lungs, which ultimately leads to death in consequence of right ventricle (RV) failure. While current drugs for PH therapy address the sustained vasoconstriction, no agent effectively targets vascular cell proliferation and tissue inflammation. Rho-associated protein kinases (ROCKs) emerged in the last few decades as promising targets for PH therapy, since ROCK inhibitors demonstrated significant anti-remodeling and anti-inflammatory effects. In this review, current aspects of ROCK inhibition therapy are discussed in relation to the treatment of PH and RV dysfunction, from cell biology to preclinical and clinical studies.


Subject(s)
Hypertension, Pulmonary/drug therapy , Protein Kinase Inhibitors/therapeutic use , rho-Associated Kinases/antagonists & inhibitors , Animals , Clinical Trials as Topic , Disease Models, Animal , Drug Approval , Humans , Protein Kinase Inhibitors/pharmacology , rho-Associated Kinases/chemistry , rho-Associated Kinases/metabolism
8.
Genet Mol Biol ; 44(1): e20200029, 2020.
Article in English | MEDLINE | ID: mdl-33395458

ABSTRACT

Brazilian Purpuric Fever (BPF) is a hemorrhagic pediatric illness caused by Haemophilus influenzae biogroup aegyptius (Hae), a bacterium that was formerly associated with self-limited purulent conjunctivitis. BPF is assumed to be eradicated. However, the virulence mechanisms inherent to Hae strains associated with BPF is still a mystery and deficient in studies. Here, we aim to analyze the role of the autotransporter genes related to adherence and colonization las, tabA1, and hadA genes through RT-qPCR expression profiling and knockout mutants. Relative quantification by real-time PCR after infection in human cells and infant rat model suggests that las was initially downregulated probably duo to immune evasion, tabA1, and hadA were overexpressed in general, suggesting an active role of TabA1 and HadA1 adhesins in Hae in vitro and in vivo. Transformation attempts were unsuccessful despite the use of multiple technical approaches and in silico analysis revealed that Hae lacks genes related to competence in Haemophilus, which could be part of the elucidation of the difficulty of genetically manipulating Hae strains.

9.
Sci Rep ; 8(1): 8290, 2018 05 29.
Article in English | MEDLINE | ID: mdl-29844457

ABSTRACT

The increase of Zika virus (ZIKV) infections in Brazil in the last two years leaves a prophylactic measures on alert for this new and emerging pathogen. Concerning of our positive experience, we developed a new prototype using Neisseria meningitidis outer membrane vesicles (OMV) on ZIKV cell growth in a fusion of OMV in the envelope of virus particles. The fusion of nanoparticles resulting from outer membrane vesicles of N. meningitidis with infected C6/36 cells line were analyzed by Nano tracking analysis (NTA), zeta potential, differential light scattering (DLS), scan and scanning transmission eletronic microscopy (SEM and STEM) and high resolution mass spectometry (HRMS) for nanostructure characterization. Also, the vaccination effects were viewed by immune response in mice protocols immunization (ELISA and inflammatory chemokines) confirmed by Zika virus soroneutralization test. The results of immunizations in mice showed that antibody production had a titer greater than 1:160 as compared to unvaccinated mice. The immune response of the adjuvant and non-adjuvant formulation activated the cellular immune response TH1 and TH2. In addition, the serum neutralization was able to prevent infection of virus particles in the glial tumor cell model (M059J). This research shows efficient strategies without recombinant technology or DNA vaccines.


Subject(s)
Bacterial Outer Membrane Proteins/immunology , Vaccines, DNA/immunology , Zika Virus Infection/prevention & control , Adjuvants, Immunologic , Animals , Antibodies, Bacterial/immunology , Antibody Formation , Brazil , Cell Line , Humans , Immunization/methods , Mice , Nanostructures , Neisseria meningitidis/immunology , Neisseria meningitidis/physiology , Vaccines, DNA/pharmacology , Zika Virus/immunology , Zika Virus Infection/immunology
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