Zika virus precursor membrane peptides induce immune response in peripheral blood mononuclear cells.

Zika virus is a re-merging flavivirus allied to serious mental health conditions in the fetuses. There is currently no preventives or treatment available for Zika infection. In this work, we have extended the in silico analysis by performing the molecular docking of previous reported three conserved Zika virus precursor membrane (prM) peptides (MP1, MP2 and MP3) with HLA complex (pHLA) and T cell receptors (TCR) and also evaluated the peptide specific immune response in human peripheral blood mononuclear cells (PBMC). Most of the CD8+ and CD4+ T cell peptides-HLA complexes demonstrated good binding energies (ΔG) and HADDOCK scores in molecular docking analysis. Immunogenic response of peptides is measured as human peripheral blood mononuclear cell (PBMC) proliferation and interferon-gamma (IFN-γ) production using a 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and a sandwich enzyme-linked immunosorbent assay (ELISA) respectively on ten different healthy blood samples. Peptide MP3 exhibited significant results in eight (cell proliferation) and seven (IFN-γ secretion) healthy volunteers' blood samples out of ten. Additionally, peptides MP1 and MP2 presented significant cell proliferation and IFN-γ release in six healthy blood samples. Thus, the outcomes from in silico and in vitro studies showed the immunogenic potential of peptides which need to validated in different experimental system before considering as candidate vaccine against Zika virus infection.

Immunoinformatics-Based Identification of the Conserved Immunogenic Peptides Targeting of Zika Virus Precursor Membrane Protein.

Zika virus infections lead to neurological complications such as congenital Zika syndrome and Guillain-Barré syndrome. Rising Zika infections in newborns and adults have triggered the need for vaccine development. In the current study, the precursor membrane (prM) protein of the Zika virus is explored for its functional importance and design of epitopes enriched conserved peptides with the usage of different immunoinformatics approach. Phylogenetic and mutational analyses inferred that the prM protein is highly conserved. Three conserved peptides containing multiple T and B cell epitopes were designed by employing different epitope prediction algorithms. IEDB population coverage analysis of selected peptides in six different continents has shown the population coverage of 60-99.8% (class I HLA) and 80-100% (class II HLA). Molecular docking of selected peptides/epitopes was carried out with each of class I and II HLA alleles using HADDOCK. A majority of peptide-HLA complex (pHLA) have HADDOCK scores found to be comparable and more than native-HLA complex representing the good binding interaction of peptides to HLA. Molecular dynamics simulation with best docked pHLA complexes revealed that pHLA complexes are stable with RMSD <5.5Å. Current work highlights the importance of prM as a strong antigenic protein and selected peptides have the potential to elicit humoral and cell-mediated immune responses.

Ocular conjunctival microbiome profiling in dry eye disease: A case control pilot study.

Purpose: Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is a multifactorial disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. A pilot study was undertaken to determine if there were any major substantial differences in the ocular microbiome in DED patients versus healthy controls. Methods: The bacterial communities residing in the conjunctiva of patients with DED (n = 4) and healthy controls (n = 4) were assessed by 16S ribosomal RNA (rRNA) gene sequencing of the V4-V5 region. Results: The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were most dominant and accounted for 97% and 94.5% of all bacterial sequences in patients and controls, respectively. At the genus level, 27 bacterial genera were found with more than two-fold difference between patients and controls. Four of these - Acinetobacter, Corynebacterium, Lactobacillus, and Pseudomonas spp. - dominated the ocular microbiome of all subjects, but were proportionately lower in DED (16.5%) compared to controls (37.7%). Several bacterial genera were found to be unique in DED (34) and controls (24). Conclusion: This pilot study is an attempt to profile the ocular microbiome in patients with DED that demonstrated a higher concentration of microbial DNA compared to controls, with Firmicutes phyla dominating the bacterial population in patients with DED.

Congenital Common Canalicular Lacrimal Fistula in an Asymptomatic Patient.

This case report discusses a diagnosis of congenital common canalicular lacrimal fistula in a 24-year-old asymptomatic patient.

North India Childhood Cataract Study - The real scenario and causes of surgical delay of pediatric cataract.

Purpose: The study sought to describe the clinical presentation pattern of pediatric cataracts and factors leading to delay in surgery at a tertiary care center in North India. Methods: A cross-sectional, interview-based study was conducted from January 2020 to October 2020, that included pediatric patients <12 years, with unilateral or bilateral congenital or developmental cataract. A pre-validated questionnaire was used to record data. The parameters recorded were age at first symptoms, age at diagnosis of cataract, age at surgery, laterality of cataract, first symptom, first family member noticing the abnormality, the morphology of cataract, association of perinatal complications, family history, systemic diseases, and cause (s) of delay in surgery. Results: A total of 89 patients were included. The mean age of subjects was 4.75(±3.51) years. A white pupil was the most common symptom (64.04%) and appeared in infancy in 30.3% of cases. Parents first detected the problem in 60.67%, and the pediatrician was the first medical contact in 11.23% of cases. The median (IQR) delay period between diagnosis of cataract and cataract surgery was 4 (3-6) months, the major causes were long GA waiting (30.33%), and delay due to systemic ill health (14.61%). Conclusion: Parental education on cataract detection is recommended to help in the timely detection and hence, improved outcomes of pediatric cataract surgery. Pediatricians, consulted for any systemic illness, have the role of the second most important contact in the detection of pediatric cataract.

Management Outcomes in Pediatric Keratoconus: Childhood Keratoconus Study.

INTRODUCTION: The Global Delphi Panel of Keratoconus (KC) and Ectatic Diseases formulated management guidelines for KC in 2015. The aim of this study was to evaluate management outcomes in pediatric KC. MATERIALS AND METHODS: Prospective, interventional study was conducted at a tertiary care hospital including KC patients aged <18 years. Based on disease severity and progression of disease, patients were prescribed either glasses or contact lenses (CLs) or underwent corneal collagen crosslinking (CXL), deep anterior lamellar keratoplasty (DALK), or penetrating keratoplasty (PK). Main Outcome Measures. Best corrected visual acuity (BCVA), manifest cylinder, maximum keratometry, thinnest corneal thickness, total higher order aberrations, and corneal hysteresis at baseline and 12 and 24 months. RESULTS: 116 eyes of 62 patients with a mean age of 14.76 ± 2.77 years were included. 32.8% of the eyes (n = 38) achieved satisfactory BCVA with glasses/CLs only. Corneal collagen crosslinking (CXL) was performed in 43.1% of the eyes (n = 50) with progressive KC and halting of progression was noted in 83.3% (n = 35) of the eyes at 2 years. 7.7% of the eyes (n = 9) were managed for acute hydrops. DALK and PK were successfully performed in 9.5% (n = 11) and 6.9% (n = 8) of the eyes with BCVA of 0.14 ± 0.09 and 0.08 ± 0.12 at 2 years, respectively. CONCLUSIONS: Pediatric KC cases with progression show good visual and aberrometric outcomes and halting of progression after CXL. DALK and PK have good outcomes. The global consensus guidelines showed good clinical utility in pediatric patients. Presence of VKC did not have an impact on the outcomes of CXL in pediatric patients.

Optimization of surgeon ergonomics with three-dimensional heads-up display for ophthalmic surgeries.

PURPOSE: To describe the variables that may be utilized in the optimization of three-dimensional heads-up surgeries (3D-HUS) for achieving better ergonomics among ophthalmic surgeons. METHODS: A.cross-sectional study was conducted at the operating room of a tertiary eye care center, equipped with an ARTEVO 800 3D surgical microscope and display monitor. The parameters noted were monitor height (MH), surgeon eye-to-floor distance (ETFD), surgeon eye-to-monitor distance (ETMD) and viewing tilt (VT) angle. The neck and eye strain of the surgeon and assistant were scored as per Borg's CR-10 scale, before and after surgeries. RESULTS: Thirty (13 right, 17 left) eye surgeries were analyzed. The minimum ETMD was 51 inches (in) and the eye strain reduced with shorter ETMD (within the range 51 inches to 83 inches).The VT and ETFD were higher for right eye surgeries. The optimum MH was between 50 and 55 in. Overall, the neck strain and eye strain were in the range of 0-3 and 0-1, respectively. CONCLUSION: The various parameters affecting the 3D image quality, neck and eye strain are chair height, VT angle, eye centration, monitor distance, laterality of the eye, and room illumination.

Clinical Data Analysis for Prediction of Cardiovascular Disease Using Machine Learning Techniques.

Cardiovascular disease is difficult to detect due to several risk factors, including high blood pressure, cholesterol, and an abnormal pulse rate. Accurate decision-making and optimal treatment are required to address cardiac risk. As machine learning technology advances, the healthcare industry's clinical practice is likely to change. As a result, researchers and clinicians must recognize the importance of machine learning techniques. The main objective of this research is to recommend a machine learning-based cardiovascular disease prediction system that is highly accurate. In contrast, modern machine learning algorithms such as REP Tree, M5P Tree, Random Tree, Linear Regression, Naive Bayes, J48, and JRIP are used to classify popular cardiovascular datasets. The proposed CDPS's performance was evaluated using a variety of metrics to identify the best suitable machine learning model. When it came to predicting cardiovascular disease patients, the Random Tree model performed admirably, with the highest accuracy of 100%, the lowest MAE of 0.0011, the lowest RMSE of 0.0231, and the fastest prediction time of 0.01 seconds.

Antiinflammatory phytochemicals against virus-induced hyperinflammatory responses: Scope, rationale, application, and limitations.

Uncontrolled inflammatory responses or cytokine storm associated with viral infections results in deleterious consequences such as vascular leakage, severe hemorrhage, shock, immune paralysis, multi-organ failure, and even death. With the emerging new viral infections and lack of effective prophylactic vaccines, evidence-based complementary strategies that limit viral infection-mediated hyperinflammatory responses could be a promising approach to limit host tissue injury. The present review emphasizes the potentials of antiinflammatory phytochemicals in limiting hyperinflammatory injury caused by viral infections. The predominant phytochemicals along with their mechanism in limiting hyperimmune and pro-inflammatory responses under viral infection have been reviewed comprehensively. How certain phytochemicals can be effective in limiting hyper-inflammatory response indirectly by favorably modulating gut microbiota and maintaining a functional intestinal barrier has also been presented. Finally, we have discussed improved systemic bioavailability of phytochemicals, efficient delivery strategies, and safety measures for effective antiinflammatory phytotherapies, in addition to emphasizing the requirement of tightly controlled clinical studies to establish the antiinflammatory efficacy of the phytochemicals. Collectively, the review provides a scooping overview on the potentials of bioactive phytochemicals to mitigate pro-inflammatory injury associated with viral infections.

Intralenticular metallic foreign body 'locked-in' the posterior capsule and the utility of multimodal imaging.

Intraocular foreign bodies (FBs) are common ocular injuries reporting to the emergency services all over the world. The authors highlight the findings and surgical management of a case of intralenticular metallic FB following an injury while using chisel and hammer. The ocular path of the FB (2 mm) could be traced from a self-sealed corneal perforation, extending through the anterior capsule rupture, terminating at the posterior capsule, forming a posterior capsule tent with a part embedded in clear lens. Preoperative ultrasound biomicroscopy gave clues on posterior capsule integrity and the exact site of FB, and helped prognosticate and plan the surgical management of the case. The 'locked-in' FB was extracted after clear lens aspiration and posterior capsulorrhexis. The posterior capsule acted as a natural barrier between anterior and posterior segment, where the FB was found embedded.

Peripheral ulcerative keratitis.

Peripheral ulcerative keratitis (PUK) is an inflammatory condition of the peripheral cornea with hallmark features of epithelial defects and stromal destruction as a result of a complex interplay of factors including host autoimmunity and the peculiar anatomic and physiologic features of the peripheral cornea and environmental factors. PUK may be the result of local or systemic causes and infectious or noninfectious causes. Arriving at a specific etiological diagnosis requires a meticulous clinical workup that may include a battery of laboratory and radiological investigations. Management by a team of internists or rheumatologists and ophthalmologists and judicious use of immunosuppressive agents may yield favorable results minimizing adverse effects. We review current clinical knowledge on the diagnosis and management of PUK.

Pediatric Keratoconus: Topographic, Biomechanical and Aberrometric Characteristics.

PURPOSE: This study sought to evaluate the demographic profile, clinical features, topographic features, and biomechanical and aberrometric characteristics in pediatric keratoconus (KC). DESIGN: Cross-sectional study. METHODS: Pediatric KC cases <18 years of age were evaluated at a tertiary hospital. Main outcome measurements were demographic profile, clinical features, visual acuity, corneal topography, aberrometry, and biomechanical and confocal microscopy findings. RESULTS: A total of 116 eyes of 62 consecutive patients were recruited with a mean ± age of 14.7 ± 2.77 years (range: 8-18 years); 46 of 62 (88%) were males; 57 of 62 cases (92%) had bilateral disease; 53 of 116 eyes (46%) had progressive KC; and 9 of 116 eyes (8%) had acute hydrops. Systemic associations were found in 6 of 62 patients (9.7%) and ocular associations in 77 of 116 eyes (66.3%); 68 of 116 eyes (58.6%) had associated vernal keratoconjunctivitis (VKC). Among eyes with VKC, 29 of 68 eyes (46%) were in stage IV KC, versus 25% of eyes with no VKC (P = .004). The mean ± SD refractive spherical equivalent was -4.72 ± 3.32 diopters (D), and refractive astigmatism was 3.69 ± 3.09 D. The mean values of maximum keratometry, thinnest pachymetry, and corneal higher-order aberrations were 60.89 ± 10.9 D, 396.05 ± 95.03 µm, and 1.18 ± 1.2 µm, respectively. Values of corneal hysteresis and corneal resistance factor correlated with the stage of KC (r = -0.26; P = .007). CONCLUSIONS: Pediatric KC was commonly associated with VKC in this cohort. Eyes with VKC had more severe KC than those without VKC. Nearly half of the patients presented with progressive disease. Corneal biomechanical changes correlated well with stage of KC in this pediatric age group.

Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA.

SARS-CoV-2 has spread very quickly from its first reported case on 19 January 2020 in the United Stated of America, leading WHO to declare pandemic by 11 March 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us to determine the rate and the regions (hotspots) of the viral genome with high rates of mutation. We analyzed the rate of mutation accumulation over a period of 11 weeks (submitted between 19th January to 15 April 2020) in USA SARS-CoV-2 genome. Our analysis identified that majority of the viral genes accumulated mutations, although with varying rates and these included NSP2, NSP3, RdRp, helicase, Spike, ORF3a, ORF8, and Nucleocapsid protein. Sixteen mutations accumulated in Spike protein in which four mutations are located in the receptor binding domain. Intriguingly, we identified a fair number of viral proteins (NSP7, NSP9, NSP10, NSP11, Envelop, ORF6, and ORF7b proteins), which did not accumulate any mutation. Limited changes in these proteins may suggest that they have conserved functions, which are essential for virus propagation. This provides a basis for a better understanding of the genetic variation in SARS-CoV-2 circulating in the US, which could help in identifying potential therapeutic targets for controlling COVID-19.

Persistent Fetal Vasculature With Subluxated Lens, Posterior Segment Pathology, and Bifid Fibrous Membrane: An Atypical Presentation.

The authors report a rare case of persistent fetal vasculature (PFV) associated with lens subluxation, axial myopia, and a thick bifid vascular stalk connecting the lens to an anomalous disc, along with medullated nerve fibers temporal to the disc. A thick fibrous membrane encasing the subluxated lens with multiple branch-like fibrovascular channels extending to the zonules was noted. This membrane with its extensions had similar histology as that of the PFV stalk. This case report adds to the understanding of PFV spectrum. [J Pediatr Ophthalmol Strabismus. 2020;57:e38-e40.].

Intraoperative aberrometry in cataract surgery with topical versus peribulbar anesthesia.

Purpose: To study the effect of choice of anesthesia on the refractive outcomes of intraoperative aberrometry (IA) for intraocular lens power calculation in cataract surgeries. Methods: This prospective, interventional nonrandomized cohort study was conducted at a tertiary care hospital between March and August 2018. A total of 178 patients with age-related cataract were allocated into two groups. Group 1 received peribulbar anesthesia using a mixture of xylocaine 2% + adrenaline 0.125 mg/ml + hyaluronidase 15 IU/ml with a 23G, 32 mm needle, while Group 2 received topical anesthesia with proparacaine hydrochloride 0.05% drops. Intraoperative aphakic measurements and IOL power calculations were obtained in all patients with the optiwave refractive analysis (ORA) system. Analysis was performed to compare the baseline parameters and postoperative manifest refraction at month 1. Results: A total of 89 patients were included in group 1 and 89 in group 2. At baseline, the axial lengths (P = 0.66) and mean keratometry (P = 0.91) were comparable. The quality measure of captured wavefront data was comparable (0.25) between the groups. Also, the postoperative mean refractive spherical equivalents were comparable between the two groups (P = 0.98) at one month. Conclusion: IA can be utilized well for cataract surgeries performed under local anesthesia with good quality of captured wavefront, provided the eye can be aligned in centre with the fixation light of ORA.

Juvenile idiopathic arthritis-related uveitis mimicking endophthalmitis.

Juvenile idiopathic arthritis (JIA) is a group of disorders occurring in children with arthritis of more than 6 weeks' duration. JIA may have varied systemic and ocular presentations, which can pose a diagnostic challenge. Chronic uveitis with insidious onset is the most common type of ocular presentation. This report highlights a case of enthesitis-related arthritis, a type of JIA, in a 12-year-old boy who presented with severe intermediate uveitis that mimicked endophthalmitis.

Bilateral Total Cataract After Intravitreal Bevacizumab Injection in Aggressive Posterior Retinopathy of Prematurity.

The authors report a rare occurrence of bilateral cataract in eyes with aggressive posterior retinopathy of prematurity after bilateral administration of intravitreal bevacizumab in a neonate, with no evidence of lens touch. Although the exact mechanism of cataractogenesis is unclear, the possibility of local drug toxicity needs to be investigated. [J Pediatr Ophthalmol Strabismus. 2019;56:e28-e30.].