Neuroinflammation and acetylcholinesterase inhibition potentials of acyclic monoterpenoids isolated from Cymbopogon distans (Nees ex Steud.) Will. Watson.

Cymbopogon distans (Nees ex Steud.) Will. Watson (Poaceae) is a promising aromatic plant distributed in the Himalayas. In this study, five acyclic monoterpenoids, namely geranyl acetate (RS1), neral (RS2), geranial (RS3), citral (RS4) and geraniol (RS5) were isolated from the essential oil of C. distans. The isolated compounds were tested for in-vitro neuroinflammation inhibitory potential in LPS-stimulated BV2 microglial cells. RS1-RS4 exhibited significant neuroinflammation inhibition without any cytotoxic effect at the dose of 10 µM. RS4, the most active anti-neuroinflammatory compound (TNF-α 31.48 ± 1.00%; IL-6 24.02 ± 0.63%; IL-1ß 42.15 ± 1.76%) was also able to inhibit acetylcholinesterase (AChE) in a dose-dependent manner. The results showed that RS4 (an isomeric mixture of neral and geranial) has the potential to inhibit neuroinflammation and AChE, which are the biomarkers of neurodegenerative disorders.

Thirteen Indians with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (MIM# 208250) is a rare monogenic disorder, characterized by early onset of camptodactyly, progressive coxa vara, bilateral arthropathy and constrictive pericarditis. The syndrome is caused by biallelic loss-of-function variants in PRG4. Deficiency of PRG4 results in progressive worsening of joint deformity with age. Thirteen individuals with CACP syndrome from eight consanguineous Indian families were evaluated. We used exome sequencing to elucidate disease-causing variants in all the probands. These variants were further validated and segregated by Sanger sequencing, confirming the diagnosis of CACP syndrome in them. Seven females and six males aged 2-23 years were studied. Camptodactyly (13/13), coxa vara (11/13), short femoral neck (11/13) and arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. Five novel disease-causing variants (c.3636G>T, c.1935del, c.1134dup, c.1699del and c.962T>A) and two previously reported variants (c.1910_1911del and c.2816_2817del) were identified in homozygous state in PRG4. We describe the phenotype and mutations in one of the large cohorts of patients with CACP syndrome, from India.

Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Feasibility of online learning among Indian students of dentistry during the CoVid-19 outbreak.

Even though there were several online dentistry academic programs available, the pandemic accelerated the development of e-learning processes and presented unprecedented obstacles to dental education. The pandemic has given rise to a technology-powered teaching style that replaced the centuries-old chalk-talk method. However, because it was a quick change, it had flaws and limitations and has caused turmoil and confusion among many educational teams, particularly in the academic sector. As a necessary consequence, this study is performed to evaluate undergraduate dental students' lived experiences, as well as their capability, willingness and frame of mind for the adoption of online teaching and learning approaches as part of blended learning. Hence, the use of online tutorials should be an effective method of providing meaningful insights for undergraduate dental students.

Sustainable Synthesis of Novel Green-Based Nanoparticles for Therapeutic Interventions and Environmental Remediation.

The advancement in nanotechnology has completely revolutionized various fields, including pharmaceutical sciences, and streamlined the potential therapeutic of many diseases that endanger human life. The synthesis of green nanoparticles by biological processes is an aspect of the newly emerging scientific field known as "green nanotechnology". Due to their safe, eco-friendly, nontoxic nature, green synthesis tools are better suited to produce nanoparticles between 1 and 100 nm. Nanoformulation of different types of nanoparticles has been made possible by using green production techniques and commercially feasible novel precursors, such as seed extracts, algae, and fungi, that act as potent reducing, capping, and stabilizing agents. In addition to this, the biofunctionalization of nanoparticles has also broadened its horizon in the field of environmental remediation and various novel therapeutic innovations including wound healing, antimicrobial, anticancer, and nano biosensing. However, the major challenge pertaining to green nanotechnology is the agglomeration of nanoparticles that may alter the surface topology, which can affect biological physiology, thereby contributing to system toxicity. Therefore, a thorough grasp of nanoparticle toxicity and biocompatibility is required to harness the applications of nanotechnology in therapeutics.

Developing a model for aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis.

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Mapping soil trace metal distribution using remote sensing and multivariate analysis.

Trace metal soil contamination poses significant risks to human health and ecosystems, necessitating thorough investigation and management strategies. Researchers have increasingly utilized advanced techniques like remote sensing (RS), geographic information systems (GIS), geostatistical analysis, and multivariate analysis to address this issue. RS tools play a crucial role in collecting spectral data aiding in the analysis of trace metal distribution in soil. Spectroscopy offers an effective understanding of environmental contamination by analyzing trace metal distribution in soil. The spatial distribution of trace metals in soil has been a key focus of these studies, with factors influencing this distribution identified as soil type, pH levels, organic matter content, land use patterns, and concentrations of trace metals. While progress has been made, further research is needed to fully recognize the potential of integrated geospatial imaging spectroscopy and multivariate statistical analysis for assessing trace metal distribution in soils. Future directions include mapping multivariate results in GIS, identifying specific anthropogenic sources, analyzing temporal trends, and exploring alternative multivariate analysis tools. In conclusion, this review highlights the significance of integrated GIS and multivariate analysis in addressing trace metal contamination in soils, advocating for continued research to enhance assessment and management strategies.

Meibography-Guided Electroepilation for Congenital Distichiasis: A Novel Surgical Technique.

PURPOSE: Congenital distichiasis is managed either by ablation, using laser, cryotherapy, or electroepilation, or by surgical excision with mucous membrane grafting. Ablative procedures are usually blind as the exact depth of distichiatic eyelashes is unknown. The described surgical technique utilizes meibography for imaging the root and depth of distichiatic eyelashes that aided in performing electroepilation. METHODS: Six patients (n = 24 eyelids; mean age 15.5 ± 12.2 years) underwent infrared meibography (Oculus Keratograph 5 M) and noninvasive tear breakup time prospectively. Eyelashes were electroepilated using a premarked needle inserted at a depth based on meibography findings in 4 patients. Surgical success was defined as no distichiatic eyelash regrowth and functional success was defined as the resolution of symptoms at a minimum of 3 months of follow-up. RESULTS: All 6 patients had all 4 eyelids involved to varying degrees, with a total of 230 distichiatic eyelashes. The median number of distichiatic eyelashes was 9 in the upper eyelids and 4.5 in the lower eyelids. Meibography revealed visible distichiatic eyelash roots in 70% of eyelashes in the upper eyelid and 87.8% in the lower eyelid, respectively. The median eyelash root depth was 2.7 mm (mean 2.9 mm, range 1.8-5.4 mm). The mean noninvasive tear breakup time was 12.2 seconds despite absent or rudimentary meibomian gland segments seen on meibography. The anatomical success was 75% (12/16 eyelids), and functional success was 87.5% (7/8 eyes) at a median follow-up of 5.5 months. CONCLUSION: Preoperative infrared meibography in eyelids with congenital distichiasis helps estimate the eyelash depth and can be used to guide eyelash ablation procedures.

Radiological Imaging of the Lacrimal Gland in Sjogren's Syndrome: A Systematic Review and Meta-Analysis.

PURPOSE: To critically appraise the evidence on the ability of the lacrimal gland ultrasonography (USG) or magnetic resonance imaging (MRI) to differentiate between Sjogren's syndrome and non-Sjogren's syndrome/healthy controls. METHODS: A systematic review and meta-analysis (based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) of online literature search was performed using PubMed, Scopus, and Cochrane databases. Cohort studies comparing the imaging features of the lacrimal glands of Sjogren's syndrome with a control group were included. Quantitative synthesis was performed using the RevMan (Version 5.4.1). RESULTS: Six studies used USG as an imaging technique, and three used MRI for the lacrimal gland imaging. The lacrimal gland affected with Sjogren's syndrome shows glandular heterogeneity on USG and MRI. Heterogeneity on USG had 6.18 times higher odds of the lacrimal gland being involved with Sjogren's syndrome (95% CI, 3.31-11.55). Gland hyperechogenicity cannot reliably differentiate the glandular involvement in Sjogren's syndrome. There is insufficient data for analysis on the gland size, hypoechoic areas, fibrous bands, and increased lacrimal artery resistance in Sjogren's syndrome patients. Of the three MRI-based studies, reduced apparent diffusion coefficient and heterogeneity were the characteristics of Sjogren's syndrome. Clinical parameters such as dry eye symptomatology and Schirmer values had variable associations with USG or MRI parameters. Ultrasonography parameters were no different between dry eye versus no dry eye in Sjogren's syndrome patients, whereas small-sized glands had low Schirmer on MRI-based studies. CONCLUSION: Glandular heterogeneity on USG is significantly associated with lacrimal gland involvement in Sjogren's syndrome patients. However, the role of radiology in predicting lacrimal gland involvement is unclear as the evidence is insufficient and heterogeneous.

Novel EGFR mutations in diffuse midline gliomas using cost-effective strategies: A report of 2 cases.

Background: Diffuse midline gliomas (DMGs) are malignant tumors predominantly affecting children, often leading to poor outcomes. The 2021 World Health Organization classification identifies 3 subtypes of DMGs, all characterized by the loss of H3K27 trimethylation. Here, we report 2 cases of DMG with Epidermal Growth Factor Receptor (EGFR) mutations within exon 20, contributing to the understanding of the molecular complexity of these pediatric brain tumors. Methods: An economical immunohistochemical panel was designed to aid in the diagnosis of most DMGs in resource-constrained regions. Sanger sequencing was employed to identify rare EGFR mutations in exon 20 of 2 cases. Results: Molecular analyses of 2 cases of DMG revealed novel EGFR mutations within exon 20. These mutations were identified using cost-effective diagnostic approaches. The presence of EGFR mutations expands the molecular landscape of DMGs and highlights the genetic heterogeneity within this tumor entity. Conclusions: These findings underscore the molecular heterogeneity of DMGs and the significance of identifying novel mutations, such as EGFR mutations in exon 20. Further research into the molecular mechanisms underlying DMGs is warranted to advance therapeutic strategies and improve outcomes for pediatric patients.

Trichiasis in cicatricial ocular surface disease: a multi-center comparison of electroepilation versus eyelash resection outcomes.

PURPOSE: To evaluate the outcomes of trichiasis (excluding entropion) management in non-trachomatous cicatricial ocular surface diseases. METHODS: This is a multicenter, retrospective study of 59 patients with trichiasis who were managed using two different techniques: electroepilation using radiofrequency (RF) cautery and eyelash resection. The assessed outcomes were residual trichiasis at 6 weeks, 6, and 12 months of follow-up and the number of procedures needed. RESULTS: 41 patients (90 eyelids) underwent electroepilation, and 18 (41 eyelids) were managed with eyelash resection. All patients belonged to either Indian or Japanese ethnicity. Most patients in both groups had Stevens-Johnson Syndrome (63.4% vs. 88.9%). The mean age (43.2 vs. 46 years), disease duration (122 vs. 192.4 months), median trichiasis grade (2 vs. 2), and involvement of upper eyelids (53/90 vs. 23/41) were similar in the two groups. At six weeks, 48.9% of eyelids that underwent electroepilation had no trichiasis, and recurrences were managed with repeat electroepilation (6 eyelids) and mucous membrane grafting (10 eyelids), and 35 eyelids opted for manual epilation, giving 67.8% success at a mean follow-up of 20 months. The eyelash resection group had 75.6% success at 6 months, and recurrences were managed using lid splitting and eyelash resection, resulting in 100% success at a mean follow-up of 79 months. More interventions were needed in the electroepilation group compared to eyelash resection. CONCLUSION: Eyelash resection of the trichiatic eyelashes achieves a better success rate than electroepilation in cicatricial ocular surface disorders. Following electroepilation, one needs multiple interventions to resolve trichiasis.

Biallelic loss of function variants in FUZ result in an orofaciodigital syndrome.

Orofaciodigital syndrome is a distinctive subtype of skeletal ciliopathies. Disease-causing variants in the genes encoding the CPLANE complex result in a wide variety of skeletal dysplasia with disturbed ciliary functions. The phenotypic spectrum includes orofaciodigital syndrome and short rib polydactyly syndrome. FUZ, as a part of the CPLANE complex, is involved in intraflagellar vesicular trafficking within primary cilia. Previously, the variants, c.98_111+9del and c.851G>T in FUZ were identified in two individuals with a skeletal ciliopathy, manifesting digital anomalies (polydactyly, syndactyly), orofacial cleft, short ribs and cardiac defects. Here, we present two novel variants, c.601G>A and c.625_636del in biallelic state, in two additional subjects exhibiting phenotypic overlap with the previously reported cases. Our findings underscore the association between biallelic loss of function variants in FUZ and skeletal ciliopathy akin to orofaciodigital syndrome.

Body composition parameters as predictors of low back pain in rural homemakers of North India.

Background: Homemakers are the backbones of families, but in rural India, females suffer from many musculoskeletal problems due to excessive workload in their houses. The objective of the present study is to compare body composition parameters as predictors of low back pain (LBP) in nonworking rural homemakers of North India. Materials and Methods: The study was conducted among 296 homemakers from rural areas of Lucknow district in Uttar Pradesh. Details of LBP and body composition parameters (body mass index, body fat, visceral fat) were taken. Results: The prevalence of LBP among homemakers was found to be 15.54%. BMI was found to be a better predictor of LBP than body fat and visceral fat. The risk of LBP is 7.24 times higher in BMI ≥23 than in women with BMI <23. The risk of LBP is 3.67 times more in visceral fat % ≥10% than in women with visceral fat % <10%. Conclusion: Age, type of family, socioeconomic status income was identified as risk factors in this population. Maintaining an adequate BMI is essential for the prevention of LBP.

A New Immortalized Human Lacrimal Gland Cell Line.

The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Two sisters with RSPRY1-related spondyloepimetaphyseal dysplasia.

Biallelic variants in RSPRY1 have been found to result in spondyloepimetaphyseal dysplasia. Two siblings presenting with short stature, facial dysmorphism, progressive vertebral defects, small epiphysis, cupping and fraying of metaphyses, brachydactyly, and short metatarsals harbored a homozygous missense variant c.1652G>A;p.(Cys551Tyr) in the RSPRY1 gene. The phenotype in our patients resembles spondyloepimetaphyseal dysplasia, Faden-Alkuraya type. Thus, our study provides further evidence to support the association of RSPRY1 variants with spondyloepimetaphyseal dysplasia. We observed joint dislocation as a novel clinical feature of this condition.