Scheimpflug-Based Corneal Biomechanical Analysis As A Predictor of Glaucoma in Eyes With High Myopia.

Purpose: To address if corneal biomechanical behavior has a predictive value for the presence of glaucomatous optical neuropathy in eyes with high myopia. Patients and Methods: This observational cross-sectional study included 209 eyes from 108 consecutive patients, divided into four groups: high myopia and primary open-angle glaucoma (POAG) - HMG, n = 53; high myopia without POAG - HMNG, n = 53; non-myopic with POAG - POAG, n = 50; non-myopic and non-POAG- NMNG, n = 53. Biomechanical assessment was made through a Scheimpflug-camera-based technology. Receiver operating characteristic curves were made for the discrimination between groups. Multivariable logistic regression models were performed to address the predictive value of corneal biomechanics for the presence of glaucoma. Results: Areas Under the Receiver Operating Characteristic (AUROCs) above 0.6 were found in 6 parameters applied to discriminate between HMG and HMNG and six parameters to discriminate between POAG and NMNG. The biomechanical models with the highest power of prediction for the presence of glaucoma included 5 parameters with an AUROC of 0.947 for eyes with high myopia and 6 parameters with an AUROC of 0.857 for non-myopic eyes. In the final model, including all eyes, and adjusted for the presence of high myopia, the highest power of prediction for the presence of glaucoma was achieved including eight biomechanical parameters, with an AUROC of 0.917. Conclusion: Corneal biomechanics demonstrated differences in eyes with glaucoma and mainly in myopic eyes. A biomechanical model based on multivariable logistic regression analysis and adjusted for high myopia was built, with an overall probability of 91.7% for the correct prediction of glaucomatous damage.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AFTER COVID-19: MULTIMODAL EVALUATION.

PURPOSE: To report the case and multimodal imaging findings of a healthy young woman who developed paracentral acute middle maculopathy 9 weeks after COVID-19. METHODS: Case report. Ultra-widefield fundus photography, macular spectral domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS: A 36-year-old woman went to the emergency department with sudden, painless, left eye vision loss. The only relevant medical history was COVID-19 9 weeks before. The best-corrected visual acuity was 20/200, a left eye relative afferent pupillary defect was present, and superficial hemorrhages throughout the macular area and peripheral retina were found. Nearly 4 hours after admission, the left eye best-corrected visual acuity recovered to 20/20 without relative afferent pupillary defect. Five days after presentation in the emergency department, the patient returned with recurrent left eye vision loss, with spontaneous recovery within 12 hours. Macular spectral domain optical coherence tomography revealed hyperreflectivity of the inner plexiform and inner nuclear layers, and the diagnosis of paracentral acute middle maculopathy was established. The patient started oral acetylsalicylic acid and oral prednisolone. The patient did not report any new episodes of vision loss, and there was a progressive resolution of abnormal fundus findings. CONCLUSION: SARS-CoV-2 infection increases the risk of vascular thrombotic events with possible involvement of the retinal circulation, and paracentral acute middle maculopathy may present as a possible complication. Ophthalmologists should be able to recognize it promptly through multimodal imaging findings.

Proteomic analysis of the secretome of HepG2 cells indicates differential proteolytic processing after infection with dengue virus.

Secretome analysis can be described as a subset of proteomics studies consisting in the analysis of the molecules secreted by cells or tissues. Dengue virus (DENV) infection can lead to a broad spectrum of clinical manifestations, with the severe forms of the disease characterized by hemostasis abnormalities and liver injury. The hepatocytes are a relevant site of viral replication and a major source of plasma proteins. Until now, we had limited information on the small molecules secreted by hepatic cells after infection by DENV. In the present study, we analysed a fraction of the secretome of mock- and DENV-infected hepatic cells (HepG2 cells) containing molecules with <10kDa, using different proteomic approaches. We identified 175 proteins, with 57 detected only in the samples from mock-infected cells, 59 only in samples from DENV-infected cells, and 59 in both conditions. Most of the peptides identified were derived from proteins larger than 10kDa, suggesting a proteolytic processing of the secreted molecules. Using in silico analysis, we predicted consistent differences between the proteolytic processing occurring in mock and DENV-infected samples, raising, for the first time, the hypothesis that differential proteolysis of secreted molecules would be involved in the pathogenesis of dengue. BIOLOGICAL SIGNIFICANCE: Since the liver, one of the targets of DENV infection, is responsible for producing molecules involved in distinct biological processes, the identification of proteins and peptides secreted by hepatocytes after infection would help to a better understanding of the physiopathology of dengue. Proteomic analyses of molecules with <10kDa secreted by HepG2 cells after infection with DENV revealed differential proteolytic processing as an effect of DENV infection.

L-amino acid oxidase activity present in fractions of Bothrops jararaca venom is responsible for the induction of programmed cell death in Trypanosoma cruzi.

Bothrops jararaca venom induces programmed cell death in epimastigotes of Trypanosoma cruzi. Here we fractionated the venom and observed that the anti-T. cruzi activity was associated with fractions that present L-amino acid oxidase (L-AAO) activity. L-AAO produces H(2)O(2), which is highly toxic. The addition of catalase to the medium, a H(2)O(2) scavenger, reverted the killing capacity of venom fractions. The anti-T. cruzi activity was also abolished when parasites were cultured in a medium without hydrophobic amino acids that are essential for L-AAO activity. These results were confirmed with a commercial purified L-AAO. Treatment for 24 h with fractions that present L-AAO activity induced parasites cytoplasmic retraction, mitochondrial swelling and DNA fragmentation, all morphological characteristics of programmed cell death. Similar changes were also observed when parasites were treated with H(2)O(2). These results indicate that H(2)O(2), the product of L-AAO reaction, induces programmed cell death explaining the anti-T. cruzi activity of B. jararaca venom.

Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom.

Cells die through a programmed process or accidental death, know as apoptosis or necrosis, respectively. Bothrops jararaca is a snake whose venom inhibits the growth of Trypanosoma cruzi epimastigote forms causing mitochondrion swelling and cell death. The aim of the present work was to determine the type of death induced in epimastigotes of T. cruzi by this venom. Parasite growth was inhibited after venom treatment, and 50% growth inhibition was obtained with 10 microg/ml. Ultrastructural observations confirmed mitochondrion swelling and kinetoplast disorganization. Furthermore, cytoplasmic condensation, loss of mitochondrion membrane potential, time-dependent increase in phosphatidylserine exposure at the outer leaflet plasma membrane followed by permeabilization, activation of caspase like protein and DNA fragmentation were observed in epimastigotes throughout a 24 h period of venom treatment. Taken together, these results indicate that the stress induced in epimastigote by this venom, triggers a programmed cell death process, similar to metazoan apoptosis, which leads to parasite death.

Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom

Cells die through a programmed process or accidental death, know as apoptosis or necrosis, respectively. Bothrops jararaca is a snake whose venom inhibits the growth of Trypanosoma cruzi epimastigote forms causing mitochondrion swelling and cell death. The aim of the present work was to determine the type of death induced in epimastigotes of T. cruzi by this venom. Parasite growth was inhibited after venom treatment, and 50 percent growth inhibition was obtained with 10 æg/ml. Ultrastructural observations confirmed mitochondrion swelling and kinetoplast disorganization. Furthermore, cytoplasmic condensation, loss of mitochondrion membrane potential, time-dependent increase in phosphatidylserine exposure at the outer leaflet plasma membrane followed by permeabilization, activation of caspase like protein and DNA fragmentation were observed in epimastigotes throughout a 24 h period of venom treatment. Taken together, these results indicate that the stress induced in epimastigote by this venom, triggers a programmed cell death process, similar to metazoan apoptosis, which leads to parasite death.