They see, they learn: Pre-COVID-19 prevalence of refractive errors in school children in suburban areas of North India.

Purpose: India has the largest population of youth in the world, thereby making them important contributors to the "India of Tomorrow". Over 80% of knowledge gained is by the visual sense, thereby making school screening programs a necessity in our country. Data from the pre-COVID era, that is, 2017-18 was collected from close to 19,000 children in Gurugram, Haryana, a tier two city in National Capital Region, India. A similar prospective observational study is planned post COVID-19 (2022-23) for further analysis to depict the impact of COVID-19 in these areas. Methods: The program They See, They Learn was set at government schools in the area of operations (district of Gurgaon, Haryana), where the children and their families were unable to afford eye care services. All children who were screened underwent a comprehensive eye examination at the school premises itself. Results: A total of 18,939 students were screened over a period of 18 months, covering a total of 39 schools in the Gurugram belt, in the first phase of the program. Eleven point eight percent (n = 2254) of all school students had some form of refractive error. Girl students were found to have a higher refractive error rate (13.3%) compared to boy students (10.1%) across the schools screened. Myopia was the most common type of refractive error. Conclusion: School students require perfect vision or else they can be discouraged and may become a major burden to the economy of any developing nation. A school screening program aiming at populations that cannot afford such basic needs like spectacles is a must in all zones of the country.

A caspase-RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans.

A cell's size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate "unwanted" cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical "lethal" size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the "cell death abnormal" phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell's commitment to the cell death fate.

In vivo labeling of endogenous genomic loci in C. elegans using CRISPR/dCas9.

Visualization of genomic loci with open chromatin state has been reported in mammalian tissue culture cells using a CRISPR/Cas9-based system that utilizes an EGFP-tagged endonuclease-deficient Cas9 protein (dCas9::EGFP) (Chen et al. 2013). Here, we adapted this approach for use in Caenorhabditis elegans . We generated a C. elegans strain that expresses the dCas9 protein fused to two nuclear-localized EGFP molecules (dCas9::NLS::2xEGFP::NLS) in an inducible manner. Using this strain, we report the visualization in live C. elegans embryos of two endogenous repetitive loci, rrn-4 and rrn-1 , from which 5S and 18S ribosomal RNAs are constitutively generated.

The painless eye: Neurotrophic keratitis in a child suffering from hereditary sensory autonomic neuropathy type IV.

Hereditary sensory autonomic neuropathy (HSAN) is a group of inherited disorders (total 5 types) that are associated with sensory dysfunction and varying degrees of autonomic dysfunction. HSAN type IV (HSAN-IV) or congenital insensitivity to pain and anhidrosis (CIPA) is a rare genetic disorder inherited in an autosomal recessive manner. We report a case of this very rare genetic disease in a 3-year-old girl child, born to a family in north India with ocular features of neurotrophic keratitis. The diagnosis was made clinically based on the hallmark features of insensitivity to pain and temperature, anhidrosis, self-mutilating behavior with multiple recurrent oral ulcers, nasal bleeds, multiple trophic ulcers over joints, and decreased intellect.

An Unusual Case of Solitary Idiopathic Pigmented Vitreous Cyst.

Vitreous cysts are a rare finding and rarely cause any visual disturbances. They are often classified as idiopathic when their etiology cannot be determined. They may be congenital or acquired and pigmented or nonpigmented. In previous reports, it has been suggested on the basis of electron microscopy that these pigmented vitreous cysts may have originated from the pigment epithelium. We present the case of a 46-year-old female, with complaints of an oval-shaped floater, causing some visual disturbance in her right eye. On examination, it was found to be a pigmented, round, and nonlobulated cyst floating freely in the vitreous cavity with no attachments to the retina. This was documented and confirmed by the fundus images and optical coherence tomography findings. Laboratory tests in the patient were found to be negative for any Toxoplasma, cysticercoids, Echinococcus, and Toxocara, among others. She was on follow-up for the past 6 months with no change or disturbance in the cyst or the retinal findings. We describe a rare case of idiopathic pigmented vitreous cyst with no persistent hyaloid artery or connection between the cyst and the ocular structures.

Etiological causes and epidemiological characteristics of patients with occupational corneal foreign bodies: A prospective study in a hospital-based setting in India.

Purpose: Corneal foreign bodies (CFBs) due to occupational exposure have been largely ignored in Indian literature, especially nonmetal workers. Our study looks at a broad range of occupations and settings that contribute to CFB in our local Indian population. The study objective was to: determine the occupations, level of education and demographics of patients presenting with CFB acquired during occupational work. Methods: Prospective hospital-based study at a tertiary eye hospital in Gurgaon, Haryana, India, within duration of 9 months. Patients presenting with CFB were asked a set of questions relating to their occupation, level of education, understanding of the potential complications of CFB, and demographics. Results: A total of 83 patients were included in the study. CFB were attributed only to males. 66% of patients were in the age group of 14--29 years. 30% of patients were in the age group 30--44 years and 4% of patients were between 45 and 60 years old. The metal work industry was responsible for 47% of presentations. The construction industry was responsible for 27% of presentations. Electricians and carpenters combined were responsible for 10% of presentations and 17% of presentations occurred in other sectors. Conclusion: CFB occur across a number of occupations in the construction industry, not just metallic workers. Among a population that is generally poorly educated and have nominal understanding of the impact that CFB can have on vision, occupational hazard education is necessary to address this problem.

Diagnosis in a case total ophthalmoplegia - where time is life.

Rhino-orbito-cerebral mucormycosis is a potentially fatal fungal infection seen in poorly controlled diabetics or immunocompromised patients who can present initially to an ophthalmologist, otorhinolaryngologist or a neurologist. The clinical presentation to an ophthalmologist may be that of painful ophthalmoplegia.The confirmation and further management of the infection requires an interdisciplinary approach. A timely diagnosis and intervention can be life-saving. This article depicts the typical fulminant course and diagnostic evaluation of rhino-orbito-cerebral mucormycosis.

Management Strategies in Rosai-Dorfman Disease: To Do or Not To Do.

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is an extremely rare non-Langerhans cell histiocytosis. Orbital involvement is even rarer and may be accompanied by lymph node involvement. Treatment options range from systemic steroids and immunosuppressants to radiation and debulking. We present a rare case of bilateral orbital sinus histiocytosis with massive lymphadenopathy with cervical and circumaortic lymphadenopathy.

Multicolor labeling in developmental gene regulatory network analysis.

The sea urchin embryo is an important model system for developmental gene regulatory network (GRN) analysis. This chapter describes the use of multicolor fluorescent in situ hybridization (FISH) as well as a combination of FISH and immunohistochemistry in sea urchin embryonic GRN studies. The methods presented here can be applied to a variety of experimental settings where accurate spatial resolution of multiple gene products is required for constructing a developmental GRN.

Combined KIT and FGFR2b signaling regulates epithelial progenitor expansion during organogenesis.

Organ formation and regeneration require epithelial progenitor expansion to engineer, maintain, and repair the branched tissue architecture. Identifying the mechanisms that control progenitor expansion will inform therapeutic organ (re)generation. Here, we discover that combined KIT and fibroblast growth factor receptor 2b (FGFR2b) signaling specifically increases distal progenitor expansion during salivary gland organogenesis. FGFR2b signaling upregulates the epithelial KIT pathway so that combined KIT/FGFR2b signaling, via separate AKT and mitogen-activated protein kinase (MAPK) pathways, amplifies FGFR2b-dependent transcription. Combined KIT/FGFR2b signaling selectively expands the number of KIT+K14+SOX10+ distal progenitors, and a genetic loss of KIT signaling depletes the distal progenitors but also unexpectedly depletes the K5+ proximal progenitors. This occurs because the distal progenitors produce neurotrophic factors that support gland innervation, which maintains the proximal progenitors. Furthermore, a rare population of KIT+FGFR2b+ cells is present in adult glands, in which KIT signaling also regulates epithelial-neuronal communication during homeostasis. Our findings provide a framework to direct regeneration of branched epithelial organs.

Sequential signaling crosstalk regulates endomesoderm segregation in sea urchin embryos.

The segregation of embryonic endomesoderm into separate endoderm and mesoderm fates is not well understood in deuterostomes. Using sea urchin embryos, we showed that Notch signaling initiates segregation of the endomesoderm precursor field by inhibiting expression of a key endoderm transcription factor in presumptive mesoderm. The regulatory circuit activated by this transcription factor subsequently maintains transcription of a canonical Wnt (cWnt) ligand only in endoderm precursors. This cWnt ligand reinforces the endoderm state, amplifying the distinction between emerging endoderm and mesoderm. Before gastrulation, Notch-dependent nuclear export of an essential ß-catenin transcriptional coactivator from mesoderm renders it refractory to cWnt signals, insulating it against an endoderm fate. Thus, we report that endomesoderm segregation is a progressive process, requiring a succession of regulatory interactions between cWnt and Notch signaling.

Gene regulatory network interactions in sea urchin endomesoderm induction.

A major goal of contemporary studies of embryonic development is to understand large sets of regulatory changes that accompany the phenomenon of embryonic induction. The highly resolved sea urchin pregastrular endomesoderm-gene regulatory network (EM-GRN) provides a unique framework to study the global regulatory interactions underlying endomesoderm induction. Vegetal micromeres of the sea urchin embryo constitute a classic endomesoderm signaling center, whose potential to induce archenteron formation from presumptive ectoderm was demonstrated almost a century ago. In this work, we ectopically activate the primary mesenchyme cell-GRN (PMC-GRN) that operates in micromere progeny by misexpressing the micromere determinant Pmar1 and identify the responding EM-GRN that is induced in animal blastomeres. Using localized loss-of -function analyses in conjunction with expression of endo16, the molecular definition of micromere-dependent endomesoderm specification, we show that the TGFbeta cytokine, ActivinB, is an essential component of this induction in blastomeres that emit this signal, as well as in cells that respond to it. We report that normal pregastrular endomesoderm specification requires activation of the Pmar1-inducible subset of the EM-GRN by the same cytokine, strongly suggesting that early micromere-mediated endomesoderm specification, which regulates timely gastrulation in the sea urchin embryo, is also ActivinB dependent. This study unexpectedly uncovers the existence of an additional uncharacterized micromere signal to endomesoderm progenitors, significantly revising existing models. In one of the first network-level characterizations of an intercellular inductive phenomenon, we describe an important in vivo model of the requirement of ActivinB signaling in the earliest steps of embryonic endomesoderm progenitor specification.