Corneal Neurotization: Essentials for The Facial Paralysis Surgeon.

Deficits in corneal innervation lead to neurotrophic keratopathy (NK). NK is frequently associated with facial palsy, and corneal damage can be accelerated by facial palsy deficits. Corneal nerves are important regulators of limbal stem cells, which play a critical role in epithelial maintenance and healing. Nonsurgical treatments of NK have undergone recent innovation, and growth factors implicated in corneal epithelial renewal are a promising therapeutic avenue. However, surgical intervention with corneal neurotization (CN) remains the only definitive treatment of NK. CN involves the transfer of unaffected sensory donor nerve branches to the affected cornea, and a variety of donor nerves and approaches have been described. CN can be performed in a direct or indirect manner; employ the supraorbital, supratrochlear, infraorbital, or great auricular nerves; and utilize autograft, allograft, or nerve transfer alone. Unfortunately, comparative studies of these factors are limited due to the procedure's novelty and varied recovery timelines after CN. Regardless of the chosen approach, CN has been shown to be a safe and effective procedure to restore corneal sensation and improve visual acuity in patients with NK.

Prevalence and causes of ocular disorders and visual impairment among preterm children in Ethiopia.

OBJECTIVE: The aim of this study was to determine the prevalence, causes of ocular disorders and visual impairment among preterm children previously admitted to neonatal intensive care units in Addis Ababa, Ethiopia. METHODS AND ANALYSIS: A prospective screening survey was conducted from February to June 2019 at the paediatric eye clinic of Menelik II Hospital. Children who were preterm at birth and who attended the eye clinic were included in the study. Data on demographic and neonatal characteristics, neonatal and maternal comorbidities and ocular disorders were collected. OR and univariate analysis were used to identify predictors of ocular diseases and visual impairment. RESULTS: There were 222 children included in the study with a mean age at presentation of 2.62 years (range 2.08-6.38 years), mean gestational age 34.11 weeks (range 30-36) weeks and mean birth weight 1941.72 g (range 953-3500 g). Nearly two-thirds had ocular disorders with refractive error (51.8%), strabismus (11.3%) and a history of retinopathy of prematurity (ROP) (7.2%) being more common. One-fourth of the children had visual impairment, and the prevalence of amblyopia was 40.1%. Uncorrected refractive errors, strabismus and ROP were causes for visual impairment. CONCLUSION: Visual impairment and amblyopia are common in Ethiopia. There is a need to develop a screening protocol for ocular disorders for preterm children to enhance early detection and prevention of childhood visual impairment.

Epidemiology of Pediatric Ocular Surface Inflammatory Diseases in the United States Using the Optum Labs Data Warehouse.

PURPOSE: To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020. METHODS: Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development. MAIN OUTCOME MEASURES: The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated. RESULTS: Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53-0.65), 0.74 (95% CI, 0.68-0.81), and 1.99 (95% CI, 1.88-2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28-7.36] to 11.80 [95% CI, 10.40-13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57-3.75; 95% CI, 2.17-4.34), male sex (OR, 1.38; 95% CI, 1.26-1.50), Asian descent (OR, 3.12; 95% CI, 2.70-3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02-1.55) were associated with POSID development. CONCLUSIONS: This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Management of vernal keratoconjunctivitis: Navigating a changing treatment landscape.

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients' quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.

A novel NPHP4 homozygous missense variant identified in infertile brothers with multiple morphological abnormalities of the sperm flagella.

PURPOSE: Asthenozoospermia is an important cause of male infertility, and the most serious type is characterized by multiple morphological abnormalities of the sperm flagella (MMAF). However, the precise etiology of MMAF remains unknown. In the current study, we recruited a consanguineous Pakistani family with two infertile brothers suffering from primary infertility due to MMAF without obvious signs of PCD. METHODS: We performed whole-exome sequencing on DNAs of the patients, their parents, and a fertile brother and identified the homozygous missense variant (c.1490C > G (p.P497R) in NPHP4 as the candidate mutation for male infertility in this family. RESULTS: Sanger sequencing confirmed that this mutation recessively co-segregated with the MMAF in this family. In silico analysis revealed that the mutation site is conserved across different species, and the identified mutation also causes abnormalities in the structure and hydrophobic interactions of the NPHP4 protein. Different bioinformatics tools predict that NPHP4p.P497R mutation is pathogenic. Furthermore, Papanicolaou staining and scanning electron microscopy of sperm revealed that affected individuals displayed typical MMAF phenotype with a high percentage of coiled, bent, short, absent, and/or irregular flagella. Transmission electron microscopy images of the patient's spermatozoa revealed significant anomalies in the sperm flagella with the absence of a central pair of microtubules (9 + 0) in every section scored. CONCLUSIONS: Taken together, these results show that the homozygous missense mutation in NPHP4 is associated with MMAF.

Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis.

Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.

Child eye health in Ethiopia: a mixed methods analysis of policy and commitment to action.

BACKGROUND: Child eye health is a serious public health issue in Ethiopia, where children under the age of 15 account for over half of the population. Our aim was to review Ethiopian health policy and practice to reveal approaches and commitment to promotion and delivery of child eye health services. METHODS: We conducted a mixed-methods situational analysis employing documentary analysis and key informant interview methods. Government publications touching on any element of child eye health were included. Key informants were eligible if they were leaders, authorities, researchers or clinicians involved in child health. Data was combined and analysed by narrative synthesis, using an adaptation of the Eye Care Situation Analysis Tool as a framework. FINDINGS: Eleven documents developed by the Ministries of Health and Education were included and interviews with 14 key informants were conducted. A focus on child eye health was lacking in key health policy documents, demonstrated by limited allocation of funds, a shortage of human resources, and a subpar referral system across all levels of child eye care. CONCLUSION: The study identified several gaps and limitations in child eye health in Ethiopia. There is a need for health policies that strengthen ownership, finance and partnerships for improved coordination, and collaboration with line ministries and other stakeholders to improve child eye health services in Ethiopia.

Exploring the knowledge, attitudes, and practice towards child eye health: A qualitative analysis of parent experience focus groups.

BACKGROUND: The majority of childhood blindness causes in low-income countries are treatable or avoidable. Parents or guardians are responsible for making decisions regarding a child's eye care. Understanding parents' awareness and perception of eye problems in crucial in helping to know parents' eye care-seeking behavior. OBJECTIVE: To determine parental knowledge, attitudes and practice regarding child eye health. METHODS: Seven focus groups were carried out in Northwest Ethiopia on knowledge, attitude and practice of parents towards child eye health. Their responses were tape-recorded and later transcribed. A thematic phenomenological approach was used for the analysis. RESULT: Seventy-one parents participated in the focus groups. Participants were aware of common eye problems like trachoma, trauma, and glaucoma. However, they were unaware of the causes and etiologies of childhood blindness. Participants perceived that eye problems could be treated with hygiene and food, and often held misconceptions about the cause of strabismus and utilization of wearing spectacles. CONCLUSION: The study revealed that parents are often unaware of the causes and etiologies of common childhood eye diseases, which has downstream effects on health-seeking behavior. Health promotion efforts, potentially through mass and social media, could be helpful to raise awareness, coupled with training of health professionals at primary and secondary health facility levels.

Corneal Neurotization: Preoperative Patient Workup and Surgical Decision-making.

Background: The use of sensory nerve transfers to the anesthetic cornea has transformed the treatment of neurotrophic keratopathy by restoring ocular surface sensation and activating dysfunctional epithelial repair mechanisms. However, despite numerous reports on surgical techniques, there is a scarcity of information on the interdisciplinary management, preoperative assessment, and surgical decision-making, which are equally critical to treatment success. Methods: This Special Topic presents a standardized, interdisciplinary preoperative workup based on our 10-year experience with corneal neurotization in 32 eyes of patients with neurotrophic keratopathy. Results: Our assessment includes a medical history review, ophthalmic evaluation, and systematic facial sensory donor nerve mapping for light touch and pain modalities. This approach enables evidence-based patient selection, optimal surgery timing, and suitable donor nerve identification, including backup options. Conclusions: Based on a decade-long experience, this special topic highlights the importance of interdisciplinary collaboration and provides a practical roadmap for optimizing patient selection and surgical decision-making in patients undergoing corneal neurotization.

Salmonella meningitis in a young child from Pakistan: a case report.

BACKGROUND: Salmonella meningitis is a rare but serious complication of Salmonella infection, primarily affecting infants, children, and immunocompromised individuals. CASE PRESENTATION: We present a case of a two-and-a-half-year-old Asian boy who developed Salmonella meningitis along with pneumonia and respiratory failure. Initially, he experienced symptoms of loose motions, fever, and irritability, which progressed to neck stiffness and brisk reflexes. Cerebrospinal fluid (CSF) analysis confirmed Salmonella typhi in the CSF. Due to the worsening condition, the patient was admitted to the intensive care unit, intubated, and switched to meropenem as the antibiotic of choice after an initial empiric therapy with ceftriaxone and vancomycin. With appropriate treatment, the patient showed significant improvement, including resolution of fever and respiratory symptoms. CONCLUSION: Management of Salmonella meningitis is often challenging primarily because of the fact that the empiric therapy for meningitis may not always provide coverage to the multi-drug resistant Salmonella species found in South Asia. Prompt administration of appropriate antibiotics based on sensitivity testing is crucial for successful management. This case emphasizes the importance of early recognition and effective management of this uncommon yet severe complication of Salmonella infection.

The Role of Sensory Innervation in Homeostatic and Injury-Induced Corneal Epithelial Renewal.

The cornea is the window through which we see the world. Corneal clarity is required for vision, and blindness occurs when the cornea becomes opaque. The cornea is covered by unique transparent epithelial cells that serve as an outermost cellular barrier bordering between the cornea and the external environment. Corneal sensory nerves protect the cornea from injury by triggering tearing and blink reflexes, and are also thought to regulate corneal epithelial renewal via unknown mechanism(s). When protective corneal sensory innervation is absent due to infection, trauma, intracranial tumors, surgery, or congenital causes, permanent blindness results from repetitive epithelial microtraumas and failure to heal. The condition is termed neurotrophic keratopathy (NK), with an incidence of 5:10,000 people worldwide. In this report, we review the currently available therapeutic solutions for NK and discuss the progress in our understanding of how the sensory nerves induce corneal epithelial renewal.

Rise in the incidence of severe pediatric blepharokeratoconjunctivitis during the COVID-19 pandemic.

Severe blepharokeratoconjunctivitis (BKC) is associated with vision loss and ocular morbidity; hence, early diagnosis and treatment are crucial. Retrospective data collection using electronic patient and billing database records of all patients <18 years of age with severe BKC between March 2010 and March 2022 was performed at the Eye Clinic at the Hospital for Sick Children in Toronto, Canada. Severe BKC was defined as including corneal inflammation, new vessel formation, scarring, thinning and lipid deposits. We excluded patients with mild or no corneal involvement, and those with other corneal pathologies. Over the study period, 257 patients were diagnosed with severe BKC (161 females), with an average age of 8 years. There was a statistically significant threefold increase in the diagnosis of severe BKC since the beginning of the COVID-19 pandemic in 2020 compared to the previous years. We speculate that the increased use of facial masks during the pandemic contributed to this significant increase.

Biallelic mutations in RNA-binding protein ADAD2 cause spermiogenic failure and non-obstructive azoospermia in humans.

STUDY QUESTION: What are some pathogenic mutations for non-obstructive azoospermia (NOA) and their effects on spermatogenesis? SUMMARY ANSWER: Biallelic missense and frameshift mutations in ADAD2 disrupt the differentiation of round spermatids to spermatozoa causing azoospermia in humans and mice. WHAT IS KNOWN ALREADY: NOA is the most severe cause of male infertility characterized by an absence of sperm in the ejaculate due to impairment of spermatogenesis. In mice, the lack of the RNA-binding protein ADAD2 leads to a complete absence of sperm in epididymides due to failure of spemiogenesis, but the spermatogenic effects of ADAD2 mutations in human NOA-associated infertility require functional verification. STUDY DESIGN SIZE DURATION: Six infertile male patients from three unrelated families were diagnosed with NOA at local hospitals in Pakistan based on infertility history, sex hormone levels, two semen analyses and scrotal ultrasound. Testicular biopsies were performed in two of the six patients. Adad2 mutant mice (Adad2Mut/Mut) carrying mutations similar to those found in NOA patients were generated using the CRISPR/Cas9 genome editing tool. Reproductive phenotypes of Adad2Mut/Mut mice were verified at 2 months of age. Round spermatids from the littermates of wild-type (WT) and Adad2Mut/Mut mice were randomly selected and injected into stimulated WT oocytes. This round spermatid injection (ROSI) procedure was conducted with three biological replicates and >400 ROSI-derived zygotes were evaluated. The fertility of the ROSI-derived progeny was evaluated for three months in four Adad2WT/Mut male mice and six Adad2WT/Mut female mice. A total of 120 Adad2Mut/Mut, Adad2WT/Mut, and WT mice were used in this study. The entire study was conducted over 3 years. PARTICIPANTS/MATERIALS SETTING METHODS: Whole-exome sequencing was performed to detect potentially pathogenic mutations in the six NOA-affected patients. The pathogenicity of the identified ADAD2 mutations was assessed and validated in human testicular tissues and in mouse models recapitulating the mutations in the NOA patients using quantitative PCR, western blotting, hematoxylin-eosin staining, Periodic acid-Schiff staining, and immunofluorescence. Round spermatids of WT and Adad2Mut/Mut mice were collected by fluorescence-activated cell sorting and injected into stimulated WT oocytes. The development of ROSI-derived offspring was evaluated in the embryonic and postnatal stages. MAIN RESULTS AND THE ROLE OF CHANCE: Three recessive mutations were identified in ADAD2 (MT1: c.G829T, p.G277C; MT2: c.G1192A, p.D398N; MT3: c.917_918del, p.Q306Rfs*43) in patients from three unrelated Pakistani families. MT1 and MT2 dramatically reduced the testicular expression of ADAD2, likely causing spermiogenesis failure in the NOA patients. Immunofluorescence analysis of the Adad2Mut/Mut male mice with the corresponding MT3 mutation showed instability and premature degradation of the ADAD2 protein, resulting in the spermiogenesis deficiency phenotype. Through ROSI, the Adad2Mut/Mut mice could produce pups with comparable embryonic development (46.7% in Adad2Mut/Mut versus 50% in WT) and birth rates (21.45 ± 10.43% in Adad2Mut/Mut versus 27.5 ± 3.536% in WT, P = 0.5044) to WT mice. The Adad2WT/Mut progeny from ROSI (17 pups in total via three ROSI replicates) did not show overt developmental defects and had normal fertility. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This is a preliminary report suggesting that ROSI can be an effective treatment for infertile Adad2Mut/Mut mice. Further assisted reproductive attempts need to be carefully examined in humans during clinical trials. WIDER IMPLICATIONS OF THE FINDINGS: Our work provides functional evidence that mutations in the ADAD2 gene are deleterious and cause consistent spermiogenic defects in both humans and mice. In addition, preliminary results show that ROSI can help Adad2Mut/Mut to produce biological progeny. These findings provide valuable clues for genetic counselling on the ADAD2 mutants-associated infertility in human males. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (32000587, U21A20204, and 32061143006), and the National Key Research and Developmental Program of China (2019YFA0802600 and 2021YFC2700202). This work was also supported by Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China. The authors declare no competing interests.

Trajectory of COVID-19 vaccine hesitancy post-vaccination and public's intention to take booster vaccines: A cross-sectional analysis.

Vaccine hesitancy (VH) is not a new phenomenon in Pakistan and is regarded as one of the primary causes of unsatisfactory vaccination campaigns. This study determined post-vaccination COVID-19 VH, factors influencing COVID-19 vaccine uptake, and public's intent to receive booster vaccinations. A cross-sectional study was conducted among adult population of Lahore, Pakistan. Participants were recruited via convenience sampling between March and May 2022. SPSS version 22 was used for the data analysis. A total of 650 participants were included in the study (age = 28.1 ± 9.7 years; male-to-female ratio nearly 1: 1). The majority of participants received Sinopharm followed by Sinovac vaccine. The top three reasons of vaccine uptake were "only vaccinated individuals are allowed at the workplace, and educational institutes" (Relative importance index (RII) = 0.749), "only vaccinated people are allowed to go to markets, malls and other public places" (RII = 0.746), and "protect myself from the infection" (RII = 0.742). The mean COVID-19 VH score was 24.5 ± 6.2 (95% CI 23.9-24.9), with not being pro-vaccines and poor economic status were the significant predictors of COVID-19 vaccine hesitancy among immunized individuals (p < .05). Acceptance of booster vaccines was negatively associated with younger age and a lower level of education. Furthermore, being pro-vaccine was associated with a greater likelihood of accepting booster vaccines (p = .001). The Pakistani public continues to express VH toward COVID-19 vaccines. Therefore, aggressive measures must be taken to combat the community factors that contribute to it.

Outcomes of cataract surgery in children who present with cataract at uveitis diagnosis.

PURPOSE: To describe the clinical and demographic characteristics of patients presenting with cataract at uveitis diagnosis treated at a single institution between 2005 and 2019 and to analyze postoperative outcomes following cataract surgery. METHODS: We retrospectively reviewed the medical records of children (<18 years of age) diagnosed with cataract at their initial uveitis presentation who subsequently underwent cataract extraction. Outcome measures were best-corrected visual acuity, number of uveitis flare-ups (cells ≥1+), and postoperative complications. RESULTS: A total of 14 children (17 eyes) were included. Mean patient age was 7.2 ± 3.9 years. Methotrexate was initiated preoperatively in 11 patients; adalimumab, in 3. Primary intraocular lens was implanted in 4 eyes. Best-corrected visual acuity improved from a mean of 0.90 ± 0.40 logMAR preoperatively to 0.50 ± 0.35 logMAR at 1 year and 0.57 ± 0.40 logMAR at mean of 6.3 ± 3.4 years postoperatively. Four eyes (24%) had a single episode of uveitis flare-up during the first postoperative year. Macular and/or disk edema was discovered in 6 eyes following cataract removal. Only 3 eyes (18%) had ocular hypertension in the first year, but glaucoma developed in subsequent years in 7 eyes (41%), 5 of which required surgery. CONCLUSIONS: In our study cohort, surgery for preexisting cataract at uveitis diagnosis resulted in improved visual acuity. Postoperative uveitis flare-ups were relatively uncommon, occurring in 4 of 17 eyes. Glaucoma was the main long-term complication.

Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

Schwann Cells Are Key Regulators of Corneal Epithelial Renewal.

Purpose: Corneal sensory nerves protect the cornea from injury. They are also thought to stimulate limbal stem cells (LSCs) to produce transparent epithelial cells constantly, enabling vision. In other organs, Schwann cells (SCs) associated with tissue-innervating axon terminals mediate tissue regeneration. This study defines the critical role of the corneal axon-ensheathing SCs in homeostatic and regenerative corneal epithelial cell renewal. Methods: SC localization in the cornea was determined by in situ hybridization and immunohistochemistry with SC markers. In vivo SC visualization and/or ablation were performed in mice with inducible corneal SC-specific expression of tdTomato and/or Diphtheria toxin, respectively. The relative locations of SCs and LSCs were observed with immunohistochemical analysis of harvested genetically SC-prelabeled mouse corneas with LSC-specific antibodies. The correlation between cornea-innervating axons and the appearance of SCs was ascertained using corneal denervation in rats. To determine the limbal niche cellular composition and gene expression changes associated with innervation-dependent epithelial renewal, single-cell RNA sequencing (scRNA-seq) of dissociated healthy, de-epithelized, and denervated cornea limbi was performed. Results: We observed limbal enrichment of corneal axon-associated myelinating and non-myelinating SCs. Induced local genetic ablation of SCs, although leaving corneal sensory innervation intact, markedly inhibited corneal epithelial renewal. scRNA-seq analysis (1) highlighted the transcriptional heterogenicity of cells populating the limbal niche, and (2) identified transcriptional changes associated with corneal innervation and during wound healing that model potential regulatory paracrine interactions between SCs and LSCs. Conclusions: Limbal SCs are required for innervation-dependent corneal epithelial renewal.

Effect Of Lead On The Skin And Health Of Female Dermatitis Patients Through Cosmetics.

BACKGROUND: Cosmetics have been a part of routine body care not only for the upper classes but also for the middle and lower classes since the dawn of civilization. Cosmetic formulations are in more demand as the public's interest in skin whitening grows. The contamination of cosmetics with heavy metals is a major concern as they containing heavy metals and pose a major risk to human health. This study looks in to the effects of Lead on human skin. METHODS: In this cross sectional study different products were examined. The matrices (scalp hair, blood, serum and nails) of reference and dermatitis cosmetic female patients (seborrhoeic dermatitis, rosacea, allergic contact dermatitis, and irritant contact dermatitis) and cosmetic samples were used in a 2:1 mixture of HNO3 (65%) and H2O2 (30%), and oxidation was performed using a microwave. The oxidized beauty and biological specimen underwent electrothermal atomic emission spectrophotometry after microwave-assisted acid digestion. The validity and precision of the methodology were verified using certified reference materials. Cosmetic products (lipstick, face powder, Eye Liner and Eye shadow) of different brands contain Pb concentrations in the ranges of 50.5-120 µg/g, 14.6-30.7 µg/g, 2.87-4.25 µg/g and 15.3-21.6 µg/g, respectively. RESULTS: In the present study, cosmetic products (lipstick (N=15), face powder (N=13), eye liner (N=11), eye shadow (N=15) and female patients with dermatitis (N=252) residing in Hyderabad city, Sindh, Pakistan, was investigated. The outcome of this investigation showed significantly higher levels of Pb in biological samples (blood and scalp hair) of different types of female dermatitis patients than in reference subjects (p<0.001). CONCLUSIONS: The cosmetic products, especially with regard to heavy metals adulteration, are in use by the female population.

Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility.

BACKGROUND: Cornichon is a functionally conserved transmembrane protein family that generally acts as a cargo-sorting receptor and cycles between the ER and the Golgi. Four Cornichon family members (CNIH1-4) have been identified. The key residues responsible for CNIH1-3 to bind to AMPA receptors are not conserved in CNIH4. Additionally, the function of CNIH1-3 in GPCR signaling is less established, while more established in case of CNIH4 protein that interact with GPCR and control their exportation. Many GPCRs are known for their essential roles in male and female gonad development. But whether CNIH4 plays a role in gametogenesis remains unknown. DESIGN: Mice carrying the Cnih4 knockout allele (Cnih4tm1a-/-) were generated by insertion of a LacZ reporter and a polyadenylation site after exon 1. Western blot, Immunofluorescence, computer-aided sperm analysis and other methods were used in the functional analysis. RESULTS: We identified that both Cnih4tm1a-/- male and female mice have normal fertility. Though, the sperm count, morphology, and motility of Cnih4tm1a-/- mice were slightly impaired compared to those of wild-type mice, the testes to body weight ratio and testicular histology were similar to those in control mice. Histological examination of Cnih4tm1a-/- ovaries detected follicles from primordial to antral stages and the numbers of follicles at each stage were also comparable to wild-type controls. Normal fertility was noticed after six-month fertility tests. That was likely due to the compensatory role of Chin3, which significantly upregulated in the Cnih4tm1a-/- mice to preserve the fertility role. CONCLUSION: Despite CNIH4 showing enriched expression in mouse germ cells, our genetic knockout studies demonstrated that CNIH4 is not essential for gametogenesis and fertility in mice although with a slight reduction in count, motility and morphology of sperm in male mice.

Minimally-Invasive Corneal Neurotization (MICN): 10 Year Update in Technique and Lessons Learned Including Novel Donor Transfer of the Great Auricular Nerve.

VIDEO PLUS SUBMISSION SUMMARY: Corneal anesthesia, caused by lack of corneal innervation, is a rare but devastating condition that can lead to neurotrophic keratopathy 1, corneal ulceration, scarring, and blindness. Minimally-Invasive Corneal Neurotization (MICN) enables transfer of regional donor sensory nerves to the cornea to provide sensation and ocular protection. Here, we provide an update on technical advances and modifications that have arisen over ten years that have refined the surgery. We provide intraoperative step by step videos of corneal neurotization, noting its critical steps, pitfalls, and caveats. This video submission will focus on the novel technique of utilizing the greater auricular nerve with a sural nerve graft extension as the donor nerve for the procedure. The steps and considerations depicted will allow surgeons to carry out corneal neurotization efficiently, safely, and effectively.