Nitric oxide: A potential etiological agent for vaso-occlusive crises in sickle cell disease.

Nitric oxide (NO), a vasodilator contributes to the vaso-occlusive crisis associated with the sickle cell disease (SCD). Vascular nitric oxide helps in vasodilation, controlled platelet aggregation, and preventing adhesion of sickled red blood cells to the endothelium. It decreases the expression of pro-inflammatory genes responsible for atherogenesis associated with SCD. Haemolysis and activated endothelium in SCD patients reduce the bioavailability of NO which promotes the severity of sickle cell disease mainly causes vaso-occlusive crises. Additionally, NO depletion can also contribute to the formation of thrombus, which can cause serious complications such as stroke, pulmonary embolism etc. Understanding the multifaceted role of NO provides valuable insights into its therapeutic potential for managing SCD and preventing associated complications. Various clinical trials and studies suggested the importance of artificially induced nitric oxide and its supplements in the reduction of severity. Further research on the mechanisms of NO depletion in SCD is needed to develop more effective treatment strategies and improve the management of this debilitating disease.

Use of discarded corneo-scleral rims to create cornea-like tissue.

BACKGROUND: Corneal disease is a major cause of blindness. Transplantation of cadaver-derived corneas (keratoplasty) is still the current therapy of choice; however, the global shortage of donor corneas continues to drive a search for alternatives. To this end, biosynthetic corneal substitutes have recently begun to gain importance. Here, we present a novel method for the generation of a cornea-like tissue (CLT), using corneo-scleral rims discarded after keratoplasty. METHODS AND RESULTS: Type I collagen was polymerized within the corneo-scleral rim, which functioned as a 'host' mould, directing the 'guest' collagen to polymerize into disc-shaped cornea-like material (CLM), displaying the shape, curvature, thickness, and transparency of normal cornea. This polymerization of collagen appears to derive from some morphogenetic influence exerted by the corneo-scleral rim. Once the CLM had formed naturally, we used collagen crosslinking to fortify it, and then introduced cells to generate a stratified epithelial layer to create cornea-like tissue (CLT) displaying characteristics of native cornea. Through the excision and reuse of rims, each rim turned out to be useful for the generation of multiple cornea-shaped CLTs. CONCLUSIONS: The approach effectively helps to shorten the gap between demand and supply of CLMs/CLTs for transplantation. We are exploring the surgical transplantation of this CLT into animal eyes, as keratoprostheses, as a precursor to future applications involving human eyes. It is possible to use either the CLM or CLT, for patients with varying corneal blinding diseases.

Prevalence and Association of Digital Eye Strain with the Quality of Sleep and Feeling of Loneliness among Female College Students in Northern India.

INTRODUCTION: Because of COVID's impact on social behavior, students have become more reliant on computer-facilitated communication to continue their studies and interact with friends. While it is known that the association between screen exposure and psychological well-being is both harmful and stronger among adolescents than younger children, what is less studied are the causal factors that may mediate the relationship. OBJECTIVES: The objectives of this study were to analyze the relationship between screen exposure and two psychological outcomes, sleep quality and loneliness, using digital eye strain as a mediating factor. Eye strain is expected to have a direct and harmful influence on psychological well-being. MATERIALS AND METHODS: A structured and validated questionnaire was transcribed and administered online. A nonrepresentative sample of 497 female college students in a North Indian city participated in the study. Digital eye strain, quality of sleep, and feeling of loneliness scores were assessed using latent class analysis. RESULTS: The selected latent model suggested that Class 2 had a high percentage of students with network issues, the problem with space and noise, and various financial hardships, which had almost doubled the rate of loneliness (53.28%) and sleep-wake difficulties (75.41%) among the students affected with computer vision syndrome (89.75%). CONCLUSION: There is an urgent need to examine the implications of digital exposure across gender and age to prevent future complications. Further, awareness for improving holistic well-being in the digital era should be promoted through various platforms.

Exploring the genetic mechanisms: SELP gene's contribution to alleviating vaso-occlusive crisis in sickle cell disease.

Sickle cell disease is a catastrophic inflammatory disorder characterized by microvascular vaso-occlusion, leading to high morbidity and increased mortality. P-selectin, a cell adhesion molecule, plays a crucial role in the pathogenesis and severity of sickle cell disease. Its expression and binding with its ligand PSGL-1 is involved in various mechanisms that contribute to inflammation and immune response, resulting in complications in sickle cell disease. Preclinical data have verified the efficacy of P-Selectin inhibition in mitigating vaso-occlusive events and severity of disease. Currently clinical trials are ongoing to evaluate the safety and efficiency of P-Selectin-targeted therapies and concede the challenges and limitations associated with their use. Despite of its proven role in reducing severity in sickle cell disease, future research should focus on identifying other novel targets within the adhesion cascade and explore combination therapies. Conducting trials and addressing concerns about accessibility are crucial steps towards fully harnessing the potential of P selectin inhibitors as a groundbreaking treatment option. This review focuses on understanding the role of p selectin and its interactions with molecules involved in inflammation providing insights about the molecular etiology, pathophysiology, and potential therapeutic targets in sickle cell disease.

Diabetes is affecting everyone everywhere.

The article titled "Accessibility and Utilization of Healthcare Services Among Diabetic Patients: Is Diabetes a Poor Man's Ailment?" gave insights into a pandemic systemic disease known as diabetes mellitus. This modern-era pandemic affects everyone, regardless of their financial background. As a result, diabetes is not a systemic disease which just involves people of low socioeconomic status.

Neuropsychiatric Manifestations of Tuberous Sclerosis and Management Options: A Narrative Review.

Importance: Tuberous sclerosis is an autosomal dominant genetic disorder that affects multiple organ systems and causes a wide range of physical manifestations. It commonly involves the brain, skin, heart, eyes, kidneys, and lungs. Individuals mostly present with neuropsychiatric symptoms, comprising a noteworthy source of morbidity and mortality.Observation: Ninety percent of individuals with tuberous sclerosis have associated neuropsychiatric manifestations including attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability, which are typically underidentified and undertreated.Conclusion and Relevance: Lack of specific guidelines for management add to the significant burden of care. An individualized, multifaceted perspective, with particular focus on cognitive and psychosocial comorbidities, is key for managing tuberous sclerosis.Prim Care Companion CNS Disord 2024;26(1):22nr03481. Author affiliations are listed at the end of this article.

Cataract surgery in children using intracameral mydriatic.

PURPOSE: To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric cataract surgery. METHODS: Consecutive children aged ≤12 years planned for cataract surgery were recruited. A commercially available premixed combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) was injected at the beginning of surgery without any topical/infusion drugs for mydriasis. Pupil sizes at various points of surgery were studied. RESULTS: We recruited 75 patients with a mean age of 24.3 ± 33.4 months (range: 1 month-11 years). Adequate mydriasis with a single injection was achieved in 93.5% (n = 73 eyes of 70 patients) without additional pharmacotherapy or intervention. The mean pupillary diameter increased from 1.8 ± 0.79 to 6.1 ± 1.4 mm after injection (mean change of 4.2 ± 1.25 mm from baseline). The mean variability in pupillary diameter was 0.73 ± 1.3 mm. In five eyes, good dilatation was not possible even after repeat injection. CONCLUSION: Fixed-dose premixed intracameral injection is effective in pupil dilatation. It alleviates the need for any topical dilators or additional intraoperative supplementation for pediatric cataract surgery.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

A single chain variable fragment antibody (Tn 64) cognate to fibronectin type III repeats promotes corneal wound healing by inhibiting fibrosis.

Corneal wound healing requires epithelial reorganization and stromal extracellular matrix (ECM) remodeling, with ECM proteins such as Tenascin C (TnC) regulating and maintaining corneal homeostasis. The N-terminal globular domain and C-terminal fibrinogen-related domains of TnC are separated by epidermal growth factor (EGF)-like repeats, and upto fifteen fibronectin type III domains (Tn fn). Overexpression of Tn fn 1-5 and its splice variants occurs in varied pathologies. We have previously used Tn64 (a single chain variable fragment antibody cognate to Tn fn 1-5) to establish roles of Tn fn 1-5 in fibrotic pathologies such as rheumatoid arthritis and posterior capsular opacification. Here, we show that Tn64 binds to Tn fn repeats 3-5 (which constitute the major site for binding of soluble fibronectin within TnC). Unlike other Tn fn domains, Tn fn 3-5 displays no inhibition of fibronectin matrix assembly. Rather, the Tn fn 3-5 construct is pro-fibrotic and elicits increased expression of fibronectin. We examined corneal epithelial as well as stromal wound healing through Tn64 binding to Tn fn 3-5, using a human corneal epithelial cell (HCEC) line, primary cultures of human corneal fibroblasts (HCFs), and an ex-vivo corneal organ culture model. Tn64 enhanced proliferation and adhesion of corneal epithelial cells, while inhibiting the migration of corneal fibroblasts and myofibroblasts. Tn64 appears to attenuate inflammation through downregulation of TNF-α, prevent corneal fibrosis by limiting fibronectin polymerization, and promote regeneration of corneal epithelia and stroma, suggesting that it could be developed as a therapeutic agent for effective anti-fibrotic corneal wound healing.

Assessment of higher demand of household energy consumption in different households in India: an inter-comparative study and solar savings valuation.

The present work focuses on a detailed inter-comparative assessment of household energy consumption (HEC) patterns for different Indian households including their living style and pattern of using clean energy fuels. This assessment has been done for cooking, heating, cooling, and transportation patterns in different households. It has been observed that the monthly income, family size, and house location have a significant effect on the monthly HEC of a specific household. Besides the complete assessment of HEC, results of the present study also show the potential of solar energy applications through which rural poor households and lower-income households can save approximately $10.77 to $14.36 monthly while urban households can save $17.95 to $29.92 monthly. Rural side medium-income households can save about $10.77 to $14.36 in cooking and about $11.97 to $16.76 monthly in space heating, cooling, and lighting, while urban medium-income households can save about $17.95 to $29.92 monthly. Likely, rural high-income households or rich households can save about $11.97 to $16.76 in cooking, and about $17.95 to $29.92 monthly in space heating, cooling, and lighting while urban high-income households can save about $29.92 to $53.86 monthly. Rich households can save up to $23.94 in cooking, and up to $95.75 monthly in space heating, cooling, and lighting. A complete formulization of the theoretical assessment of HEC has been discussed in this study.

Risk of Corneal Transplant Rejection Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

INTRODUCTION: The COVID-19 pandemic has initiated an unparalleled global vaccination campaign, raising concerns about the vaccine's effects on various health conditions, including the risk of corneal transplant rejection. This systematic review aimed to identify the relationship between COVID-19 vaccination and rejection of corneal transplant, filling a significant gap in the existing medical literature. METHODS: A literature search was performed across multiple databases up to February 12, 2024, to identify studies evaluating the risk of corneal transplant rejection post-COVID-19 vaccination. Eligible studies were original research that reported outcomes of corneal graft rejection following vaccination. Nested Knowledge web software facilitated screening and data extraction. The Newcastle-Ottawa Scale was employed for quality assessment. A meta-analysis was conducted to calculate the aggregated relative risk (RR) utilizing R software version 4.3. RESULTS: Six studies were included in the qualitative synthesis, with four meeting the criteria for meta-analysis. These studies varied in geographic location, surgical techniques, and types of vaccines used. The pooled RR for corneal transplant rejection following COVID-19 vaccination was 0.816 (95% CI 0.178-1.453), indicating no significant risk of rejection. No statistical heterogeneity was observed among the studies (I2 = 0%). CONCLUSIONS: This review and meta-analysis found no significant evidence that COVID-19 vaccination increases the risk of corneal graft rejection. However, the current evidence is insufficient to conclusively determine the vaccine's safety for corneal transplant recipients. These findings underscore the need for additional research to confirm these preliminary results and investigate the long-term effects of COVID-19 vaccination on corneal transplants, aiming to provide evidence-based guidance to healthcare providers and patients.

Effect of Intravenous Mannitol on Intraocular Pressure Changes in Vitrectomized and Non-Vitrectomized Eyes: A Systematic Review and Meta-Analysis.

PURPOSE: Intraocular pressure (IOP) control is paramount during ophthalmic surgeries to ensure successful outcomes and prevent complications. Intravenous mannitol has been explored for its ability to manage IOP fluctuations in both vitrectomized and non-vitrectomized eyes. This meta-analysis aimed to assess the efficacy of mannitol in controlling IOP across these patient groups. DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted across PubMed, EMBASE, Scopus, and Web of Science from inception up to March 1, 2024, focusing on studies investigating mannitol's impact on IOP in vitrectomized and non-vitrectomized eyes. Randomized controlled trials, cohort studies, and case-control studies were included, while case reports and review articles were excluded. The primary outcome was the change in IOP following mannitol administration. Meta-analysis was performed using a random-effects model. R software (V 4.3) was used for statistical analysis. RESULTS: Our search included five studies of both vitrectomized (145 eyes) and non-vitrectomized eyes (91 eyes). The meta-analysis demonstrated significant IOP reductions following mannitol administration across multiple time points. Three studies were included at 30 min and 2 studies at all other time points in the analysis. In vitrectomized eyes, notable decreases were observed: at 30 min, the Ratio of Means (ROM) was 0.81 (95% CI: 0.53; 1.24), indicating a 19% reduction; at 60 min, the ROM of 0.833 (95% CI: 0.77; 0.89) showed a 16.7% reduction; at 90 min, the ROM of 0.757 (95% CI: 0.755; 0.758) corresponded to a 24.3% reduction; at 2 h, the ROM of 0.726 (95% CI: 0.642; 0.820) reflected a 27.4% reduction; at 3 h, the ROM of 0.692 (95% CI: 0.600; 0.797) resulted in a 30.8% reduction; and at 4 h, the ROM of 0.700 (95% CI: 0.363; 1.350) indicated a 30% reduction. No significant changes were observed on IOP with mannitol administration when comparing vitrectomized versus non- vitrectomized eyes. CONCLUSION: Intravenous mannitol effectively reduces IOP in both vitrectomized and non-vitrectomized eyes, demonstrating its utility in the acute management of elevated IOP during and after ophthalmic surgeries. These findings support the integration of mannitol into perioperative care protocols. However, further research, particularly randomized controlled trials and studies with broader demographic representation, is needed to optimize mannitol's usage and fully understand its long-term safety and efficacy.

Incidence and Association of Uveitis with COVID-19 Vaccination: A Systematic Review and Meta-Analysis.

PURPOSE: In the wake of the COVID-19 pandemic, vaccines have been pivotal in curbing disease spread and severity. However, concerns over post-vaccination adverse events, including uveitis, an inflammatory ocular condition, have been noted. This systematic review and meta-analysis aimed to evaluate the incidence and association of uveitis following COVID-19 vaccination. METHODS: A literature search was performed across several databases on October 21, 2023. Human studies examining the incidence of uveitis post-COVID-19 vaccination were included. The Newcastle-Ottawa Scale was used for quality appraisal of the included studies. Meta-analysis was performed to assess the overall incidence of uveitis and the relative risk of developing the condition post-vaccination. All statistical analyses were performed using R software version 4.3. RESULTS: Six studies involving over 2 billion vaccine doses were included. The overall incidence of uveitis was 0.016% (95% CI: 0.010 to 0.026). No significant association was found between vaccination and the onset of uveitis (Relative Risk: 1.45 (95% CI: 0.82 to 2.57, p = 0.12) from four studies. The evidence quality was rated very low due to the limited number of studies and imprecision. CONCLUSION: This analysis indicates a low incidence of uveitis following COVID-19 vaccination and no significant association with the vaccine. The findings are constrained by the small number of studies and low certainty of evidence, underscoring the need for further research. Comprehensive and longitudinal studies are necessary to confirm these findings and reinforce public confidence in COVID-19 vaccination programs.

Reference genome of the nutrition-rich orphan crop chia (Salvia hispanica) and its implications for future breeding.

Chia (Salvia hispanica L.) is one of the most popular nutrition-rich foods and pseudocereal crops of the family Lamiaceae. Chia seeds are a rich source of proteins, polyunsaturated fatty acids (PUFAs), dietary fibers, and antioxidants. In this study, we present the assembly of the chia reference genome, which spans 303.6 Mb and encodes 48,090 annotated protein-coding genes. Our analysis revealed that ~42% of the chia genome harbors repetitive content, and identified ~3 million single nucleotide polymorphisms (SNPs) and 15,380 simple sequence repeat (SSR) marker sites. By investigating the chia transcriptome, we discovered that ~44% of the genes undergo alternative splicing with a higher frequency of intron retention events. Additionally, we identified chia genes associated with important nutrient content and quality traits, such as the biosynthesis of PUFAs and seed mucilage fiber (dietary fiber) polysaccharides. Notably, this is the first report of in-silico annotation of a plant genome for protein-derived small bioactive peptides (biopeptides) associated with improving human health. To facilitate further research and translational applications of this valuable orphan crop, we have developed the Salvia genomics database (SalviaGDB), accessible at https://salviagdb.org.