Role of intra-tumoral vasculature imaging features on susceptibility weighted imaging in differentiating primary central nervous system lymphoma from glioblastoma: a multiparametric comparison with pathological validation.

PURPOSE: Primary objective of this study was to retrospectively evaluate the potential of a range of qualitative and quantitative multiparametric features assessed on T2, post-contrast T1, DWI, DCE-MRI, and susceptibility-weighted-imaging (SWI) in differentiating evenly sampled cohort of primary-central-nervous-system-lymphoma (PCNSL) vs glioblastoma (GB) with pathological validation. METHODS: The study included MRI-data of histopathologically confirmed ninety-five GB and PCNSL patients scanned at 3.0 T MRI. A total of six qualitative features (three from T2 and post-contrast T1, three from SWI: thin-linear-uninterrupted-intra-tumoral-vasculature, broken-intra-tumoral-microvasculature, hemorrhage) were analyzed by three independent radiologists. Ten quantitative features from DWI and DCE-MRI were computed using in-house-developed algorithms. For qualitative features, Cohen's Kappa-interrater-variability-analysis was performed. Z-test and independent t-tests were performed to find significant qualitative and quantitative features respectively. Logistic-regression (LR) classifiers were implemented for evaluating performance of individual and various combinations of features in differentiating PCNSL vs GB. Performance evaluation was done via ROC-analysis. Pathological validation was performed to verify disintegration of vessel walls in GB and rim of viable neoplastic lymphoid cells with angiocentric-pattern in PCNSL. RESULTS: Three qualitative SWI features and four quantitative DCE-MRI features (rCBVcorr, Kep, Ve, and necrosis-volume-percentage) were significantly different (p < 0.05) between PCNSL and GB. Best diagnostic performance was observed with LR classifier using SWI features (AUC-0.99). The inclusion of quantitative features with SWI feature did not improve the differentiation accuracy. CONCLUSIONS: The combination of three qualitative SWI features using LR provided the highest accuracy in differentiating PCNSL and GB. Thin-linear-uninterrupted-intra-tumoral-vasculature in PCNSL and broken-intra-tumoral-microvasculature with hemorrhage in GB are the major contributors to the differentiation.

CHTF18 ensures the quantity and quality of the ovarian reserve†.

The number and quality of oocytes, as well as the decline in both of these parameters with age, determines reproductive potential in women. However, the underlying mechanisms of this diminution are incompletely understood. Previously, we identified novel roles for CHTF18 (Chromosome Transmission Fidelity Factor 18), a component of the conserved Replication Factor C-like complex, in male fertility and gametogenesis. Currently, we reveal crucial roles for CHTF18 in female meiosis and oocyte development. Chtf18-/- female mice are subfertile and have fewer offspring beginning at 6 months of age. Consistent with age-dependent subfertility, Chtf18-/- ovaries contain fewer follicles at all stages of folliculogenesis than wild type ovaries, but the decreases are more significant at 3 and 6 months of age. By 6 months of age, both primordial and growing ovarian follicle pools are markedly reduced to near depletion. Chromosomal synapsis in Chtf18-/- oocytes is complete, but meiotic recombination is impaired resulting in persistent DNA double-strand breaks, fewer crossovers, and early homolog disjunction during meiosis I. Consistent with poor oocyte quality, the majority of Chtf18-/- oocytes fail to progress to metaphase II following meiotic resumption and a significant percentage of those that do progress are aneuploid. Collectively, our findings indicate critical functions for CHTF18 in ensuring both the quantity and quality of the mammalian oocyte pool.

Quantitative Measurement of Histone Tail Acetylation Reveals Stage-Specific Regulation and Response to Environmental Changes during Drosophila Development.

Histone modification plays a major role in regulating gene transcription and ensuring the healthy development of an organism. Numerous studies have suggested that histones are dynamically modified during developmental events to control gene expression levels in a temporal and spatial manner. However, the study of histone acetylation dynamics using currently available techniques is hindered by the difficulty of simultaneously measuring acetylation of the numerous potential sites of modification present in histones. Here, we present a methodology that allows us to combine mass spectrometry-based histone analysis with Drosophila developmental genetics. Using this system, we characterized histone acetylation patterns during multiple developmental stages of the fly. Additionally, we utilized this analysis to characterize how treatments with pharmacological agents or environmental changes such as γ-irradiation altered histone acetylation patterns. Strikingly, γ-irradiation dramatically increased the level of acetylation at H3K18, a site linked to DNA repair via nonhomologous end joining. In mutant fly strains deficient in DNA repair proteins, however, this increase in the level of H3K18 acetylation was lost. These results demonstrate the efficacy of our combined mass spectrometry system with a Drosophila model system and provide interesting insight into the changes in histone acetylation during development, as well as the effects of both pharmacological and environmental agents on global histone acetylation.

Comparative Evaluation of Sealing Ability of Different Type of MTA as Root-End Filling Materials Using Dye Penetration Technique - An In Vitro Study.

Introduction: The main goal of the root-end filling material is to create a hermetic seal to protect against microbes and their by-products. Excellent biocompatibility and sealing ability are characteristics of MTA developed by Torabinejad et al. This study aimed to compare the sealing ability of different type MTA as root-end filling material using dye penetration technique. Material and Method: One-twenty (N = 120) extracted human maxillary anterior teeth were decontaminated, cleaned, and decoronated. Endodontic treatment and root-end resection were done. Then root-end cavity was prepared and filled with tested materials (N = 30). A calibrated stereomicroscope was used to evaluate linear measurement. All data were tabulated and statistically analyzed with a level of significance set at P < .05. Result: This order of increasing microleaks was observed: MTA Angelus < MTA Plus < PRO-Root MTA < Control group. There was a statistically significant difference in mean microleakage in MTA Angelus and MTA Plus groups (P = 0.040). MTA Angelus shows the least microleakage among all the bioceramic material groups. Conclusion: Although the sealing ability of MTA Angelus is superior to MTA Plus, PRO-Root MTA. MTA Plus, PRO-Root MTA could be considered an acceptable alternative to MTA Angelus in peri-radicular surgeries.

Morphological Variation of Mandibular Molars in Rohilkhand Population: An Original Research.

Introduction: In-depth knowledge of common and aberrant pulp morphology is essential for appropriate diagnosis and treatment planning before commencing root canal treatment. The radicular morphology of mandibular molars has been extensively studied. Considerable variation in the number of canals and roots found in these teeth has been reported. Aim: The purpose of this study is to investigate the root canal morphology of the mandibular molars among the Rohilkhand population using Dentascan. Materials and Methods: Dentascan images of mandibular molar were taken from 99 extracted teeth that were collected from the Department of Oral Surgery and Maxillofacial Surgery, Institute of Dental Sciences, Bareilly, and private clinics. The examination of root canal systems of the teeth was based on Vertucci's classification. Results: The mandibular molar (n = 99) were taken. Out of the 99 teeth examined, three canals were seen in 60 (60.6%) teeth, four canals in 39 (39.4%) teeth, 3% had extra distal roots, and 6% with C-shaped canals. Conclusion: Among mandibular first molars, only 3% had three roots. Mesial roots of the first molar typically present with two canals and two apical foramina with type IV or II canal configuration. Most distal roots of the first molar presented with a type I canal configuration. The remainder were distributed mainly between types II, IV, III, and V. Among 99 mandibular molars, 6% had single C-shaped roots.

Numerical Analysis of Coronavirus Detection Using Photonic Crystal Fibre-Based SPR Sensor.

Coronavirus disease (COVID-19) is a worldwide health emergency caused by the coronavirus 2 (severe acute respiratory illness) (SARS-CoV-2). COVID-19 has a wide range of symptoms, making a definitive diagnosis difficult. The shortage of equipment for testing technology COVID-19 has resulted in long queues for COVID-19 testing, which is a major problem. COVID-19 testing is currently performed using sluggish and costly technology like single-photon emission computed tomography (SPECT), computed tomography (CT), positron emission tomography (PET), and enzyme-linked immunosorbent assay (ELISA). The gold standard test for diagnosing COVID-19 is real-time reverse transcriptase-polymerase chain reaction (RT-PCR), which necessitates highly skilled workers and has a lengthy turnaround time. However, rapid and affordable immunodiagnostic techniques (antigen or antibody tests) are also available with some trade off accuracy. Optical sensors are frequently employed in a variety of applications, because of their increased sensitivity, strong selectivity, rapid reaction times, and outstanding resolution. The use of photonic crystal fibre (PCF) is advantageous for the quick detection of the new coronavirus and is suggested with the use of a PCF-based (Au/BaTiO3/graphene) multilayered surface plasmon resonance (SPR) biosensor. The proposed sensor can quickly detect the COVID-19 virus in two different ligand-analyte environments: (i) the virus spike receptor-binding domain (RBD) as an analyte and monoclonal antibodies (mAbs) as a probe ligand, and (ii) monoclonal antibodies (IgG or IgM) as an analyte and the virus spike RBD as a probe ligand. The finite element method (FEM) is used to quantitatively examine the performance of the PCF-based multilayered SPR sensor.

Evaluation of phytoconstituents of Tinospora cordifolia against K417N and N501Y mutant spike glycoprotein and main protease of SARS-CoV-2- an in silico study.

Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.

Is ultra-thin Descemet stripping automated endothelial keratoplasty a viable alternative to Descemet membrane endothelial keratoplasty? A systematic review and meta-analysis.

Background: Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various corneal endothelial diseases. Objectives: To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK). Design: A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome. Methods: We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4. Results: A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95% CI: 0.04-0.09) in BCVA, albeit with i 2 of 52% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95% CI: 0.13-0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95%CI: -133.09 to -305.77). Conclusion: Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells.

Ferroptosis is a caspase-independent form of regulated cell death strongly linked to the accumulation of reactive lipid hydroperoxides. Lipid hydroperoxides are neutralized in cells by glutathione peroxidase 4 (GPX4) and inhibitors of GPX4 are potent ferroptosis inducers with therapeutic potential in cancer. Here we report that siRNA-mediated silencing of the AMPK-related kinase NUAK2 suppresses cell death by small-molecule inducers of ferroptosis but not apoptosis. Mechanistically we find that NUAK2 suppresses the expression of GPX4 at the RNA level and enhances ferroptosis triggered by GPX4 inhibitors in a manner independent of its kinase activity. NUAK2 is amplified along with MDM4 in a subset of breast cancers, particularly the claudin-low subset, suggesting that this may predict vulnerability to GPX4 inhibitors. These findings identify a novel pathway regulating GPX4 expression as well as ferroptotic sensitivity with potential as a biomarker of breast cancer patients that might respond to GPX4 inhibition as a therapeutic strategy.

Effect of laser peripheral iridotomy on contrast sensitivity using Spaeth/Richman Contrast Sensitivity test.

BACKGROUND: Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast sensitivity (CS) after the procedure. OBJECTIVE: This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test. METHODS: We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI. RESULTS: Data analyses revealed female predominance (66.67%, 20/30); the mean age of enrolled patients was 49.93 ± 10.43 years, and presenting acuity was 0.02 ± 0.06 (Log of Minimum Angle of Resolution [LogMAR]). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 ± 0.09, -2.36 ± 1.72 and 2.34 ± 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 ± 3.83 mmHg) and 2 weeks post-LPI (11.70 ± 1.53 mmHg) IOP (p < 0.001). However, CS in the pre- (73.47 ± 9.88) and 3 months post-LPI (75.20 ± 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients. CONCLUSION: LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.

Conjunctival and Corneal Fibrous Histiocytoma: Brief review.

Background: Fibrous histiocytoma (FH), a mesenchymal tumour, usually have an orbital presentation. Rarely, FH in both benign and malignant forms have been reported at limbus and conjunctiva. Present narrative review was conducted to determine demographic profile, clinical presentation and management options for this rare tumour.Methods: PubMed database was searched to identify articles presenting with fibrous histiocytoma of conjunctiva, cornea and limbus. Data was tabulated for age of presentation, sex, eye involved, area of involvement, if tumor was benign or malignant, management and recurrences.Results: Total of 35 articles were selected, which included 42 cases, of which 27 were benign and 15 malignant. 25 cases showed presence of limbal FH, 12 conjunctival, 4 caruncular and 1 corneal FH. Mean age of presentation was 30.9 years with male preponderance (females-10, males-17) in benign FH while malignant FH presented with mean age of 44.5 years and sex distribution of 7 females and 8 males. 4 cases of benign FH showed recurrence, which required re-excision and immunotherapy, while recurrence in malignant FH was 60%, where 4 needed exenteration, 3 enucleation and 1 expired due to metastasis.Conclusion: FH is one of the rare ocular tumours of eye presenting usually at the limbus and conjunctiva and rarely cornea. Histopathological examination along with immunostaining has a definite role in the diagnosis. Surgical excision with tumour free margins is the corner stone of treatment. Recurrences in benign varieties need re-excision or immunotherapy, while malignant cases need aggressive surgical options like exenteration or enucleation.

Protocol for evaluating autophagy using LysoTracker staining in the epithelial follicle stem cells of the Drosophila ovary.

We have outlined the approach of visualizing autophagy specifically in the epithelial follicle stem cells of the Drosophila ovary using the LysoTracker dye. The advantage of using this protocol is that it details several techniques, including ovary dissection, immunofluorescence, and western blotting, that positively identify autophagy changes in a very small population of cells. One of the limitations of this protocol is that it needs to be combined with other genetic manipulations and positive markers of the autophagy pathway. For complete details on the use and execution of this protocol, please refer to Singh et al., (2018).

Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1.

Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

Evaluation of safety and efficacy of different protocols of collagen cross linking for keratoconus.

Introduction: Collagen cross-linking is a well-established modality that could stop the keratoconus from progressing. Off late, newer protocols have been suggested for progressive keratoconus, which include the use of hypoosmolar riboflavin for thinner corneas and the use of accelerated CXL protocol to reduce the effective treatment time. Objective: To assess the safety and efficacy of different protocols of conventional CXL, hypoosmolar CXL and accelerated CXL in patients with keratoconus. Materials & methods: It was a prospective, interventional study with minimum of 12 months follow-up. Patients were divided into 3 groups; conventional CXL, CXL using hypotonic riboflavin and accelerated CXL group. Primary outcome measures - For efficacy, Sim Kmax and Sim Kmin (Progression (Kmax > +1 D), stabilization (Kmax +1 D to -1 D) and regression (Kmax > -1 D). For safety - endothelial count evaluation (decrease >10% amounted to compromise the safety of the procedure). Secondary outcome measures - BCVA and adverse events. Results: 32 eyes underwent isotonic CXL treatment. Pre-treatment and post-treatment BCVA were 0.16 +/- 0.15 and 0.10 +/- 0.11 log MAR; specular counts 2782.81 +/- 307.25 (cells/ mm2) and 2708.5 +/- 263.27 (cells/ mm2) (p=0.05); KMax values 55.31 +/- 4.12 D and 53.9 +/- 3.77 D (p=0.0001). 16 eyes underwent hypotonic CXL treatment. Pre-treatment and post-treatment BCVA were 0.15 +/- 0.13 log MAR and 0.14 +/- 0.14; specular count 2701.19 +/- 243.25 (cells/ mm2) and 2713.5 +/- 369 (cells/ mm2) (p= 1) and KMax values 54.74 +/- 7.44 D and 52.74 +/- 6.76 D (p = 0.002). 15 eyes underwent accelerated CXL treatment. Pre-treatment and post-treatment BCVA were 0.16 +/- 0.15 and 0.10 +/- 0.12 log MAR; specular counts 2967.53 +/- 356.48 and 2893.07 +/- 336.55 (cells/ mm2) (p = 0.78) and KMax values 55.19 +/- 5.46 D and 54.24 +/- 5.33 D (p = 0.337). Conclusion: All three protocols appeared safe and efficacious as therapeutic regimen for progressive keratoconus.

Correlation of Ocular Surface Disease and Quality of Life in Indian Glaucoma Patients: BAC-preserved versus BAC-free Travoprost.

Objectives: The use of benzalkonium chloride (BAC)-preserved medications is associated with ocular surface disease (OSD) that can negatively affect quality of life (QoL) in glaucoma patients. This study aimed to compare QoL and correlate it with OSD in glaucoma patients receiving BAC-preserved and BAC-free travoprost. Materials and Methods: A total of 110 subjects were divided into 3 groups: 40 primary open-angle glaucoma (POAG) patients using BAC-preserved travoprost, 40 POAG patients using BAC-free travoprost, and 30 age-matched controls. All patients were assessed using a single interviewer-administered format of the Ocular Surface Disease index (OSDI) and Glaucoma Quality of Life-15 (GQL-15) questionnaires. Results: Mean GQL-15 score in the BAC group was significantly higher than in the BAC-free group (24.71±7.42 vs. 17.58±3.06; p<0.05). The mean difference in GQL-15 scores between controls and the BAC-free group (1.24) was insignificant (p>0.05). There was a strong positive correlation between OSDI scores and GQL-15 scores in all the groups (r values: BAC: 0.63, BAC-free: 0.23, controls: 0.29), with higher OSDI scores (severe OSD) associated with higher GQL-15 scores (worse QoL). Cronbach's alpha was 0.84 for GQL-15 and 0.75 for OSDI. Conclusion: BAC-preserved travoprost leads to higher OSDI scores, which correlate strongly with poor QoL scores as compared to BAC-free travoprost. The use of BAC-free formulations should be encouraged to reduce the onset or worsening of OSD and impaired QoL in glaucoma patients.

Assessing glaucoma deterioration using Spaeth/Richman contrast sensitivity test.

PURPOSE: To assess changes in the central and peripheral contrast sensitivity in severe primary open-angle glaucoma (POAG) patients using a computer-based Spaeth/Richman contrast sensitivity test (SPARCS) over a period of 24 months. METHODS: Our pilot, observational study included 15 patients (30 eyes) with severe POAG. Visual acuity, intraocular pressure, number of anti-glaucoma drugs, visual fields, and SPARCS score were recorded at first visit and at 12 and 24 months. RESULTS: We observed changes in mean deviation (MD) from -19.37 ± 5.04 to -20.63 ± 4.07, mean pattern standard deviation (PSD) from 11.49 ± 2.61 to 11.35 ± 2.01, and mean SPARCS score from 54.97 ± 15.66 to 53.50 ± 16.42. We found no statistically significant difference between visual field parameters and SPARCS scores associated with the number or type of prescribed anti-glaucoma drugs. Spearman's correlation coefficient of SPARCS at baseline (SPARCS1) versus MD at baseline (MD1) was 0.274 (p = 0.142) and SPARCS1 versus PSD at baseline (PSD1) was -0.163 (p = 0.389). The correlation coefficient between SPARCS at 12 months (SPARCS2) versus MD (MD2) at the same time point was computed to be 0.391 (p = 0.03), whereas SPARCS2 versus PSD at 12 months was -0.212 (p = 0.262). Similarly, we found the coefficient to be 0.336 (p = 0.069) for SPARCS3 (SPARCS at 24 months) versus MD3 (MD at 24 months) and -0.242 (p = 0.197) for SPARCS3 versus PSD3 (PSD at 24 months). Correlation coefficients between SPARCS1/2, SPARCS1/3, MD1/2, MD1/3 PSD1/2, and PSD1/3 were 0.856, 0.865, 0.748, 0.722, 0.497, and 0.562, respectively (p < 0.001). MD changed by 9.46% ± 12.73%, PSD by 0.64% ± 14.03%, and average SPARCS by 3.31% ± 12.73% over 24 months. CONCLUSION: The data from our study indicate the utilitarian application of SPARCS, an inexpensive and readily available tool for monitoring functional deterioration in cases with advanced glaucomatous damage, especially in resource-poor settings. Furthermore, it is a useful and reliable alternative to the imaging modalities where retinal nerve fiber layer measurement can be erroneous in advanced cases secondary to the floor effect.

A rare case of benign fibrous histiocytoma of the cornea.

Fibrous histiocytoma (FH) commonly occurs in the superficial layers of the skin. Orbit and limbus are documented ophthalmic sites of involvement but isolated corneal FH has never been reported in literature. We present the first case of FH exclusively involving the cornea where a 10-year-old male child presented with a 3-month history of a painless growth on the superior cornea of the right eye with deterioration of vision. Tumor excision with therapeutic penetrating keratoplasty was done and the histopathological examination confirmed the diagnosis. There was no recurrence and the corneal graft was clear at 1 year.

Ocular Surface Disease with BAK preserved Travoprost and Polyquaternium 1(Polyquad) preserved Travoprost.

Introduction. The topical medications containing benzalkonium chloride (BAK) as preservative is known to induce corneal toxicity and ocular surface disease (OSD) in glaucoma patients. Newer preservatives like SofZia or polyquaternium-1 (Polyquad) have been developed to replace BAK in many medications. The present study aimed at comparing the OSD in glaucoma patients receiving BAK preserved travoprost versus travoprost with polyquad as preservative and controls not receiving any medications. Methods. This prospective, controlled, observational study was conducted on patients of primary open angle glaucoma (POAG) on medications for more than 6 months. The first group comprised of 40 patients receiving BAK preserved travoprost, the second group included 40 patients receiving polyquad preserved travoprost and 30 of control group not receiving any medical treatment. Ocular Surface Disease Index (OSDI) scores using Ocular Surface Disease Index (OSDI) Questionnaire were assessed and compared in all subjects. Results. The mean OSDI score was 29.09 ± 13.45 in BAK group, 12.4 ± 5.085 in polyquad group and 10.93 ± 7.36 in controls. The mean difference in OSDI scores between BAK and polyquad group 16.63 (p < 0.05) and between the BAK and control group was 18.96 (p < 0.05). The mean difference in OSDI scores between the polyquad and control group was 1.53 (p > 0.05). The mean IOP in the BAK group was 19.2 ± 3.5 and in polyquad group was 20.1 ± 4.2. The IOP measured at 12 months of treatment was 13.2 ± 2.1 in BAK group and 12.8 ± 3.3 in polyquad group. The IOP measured at baseline and 12 months showed statistically significant difference in both the groups (p

The NuA4 acetyltransferase and histone H4 acetylation promote replication recovery after topoisomerase I-poisoning.

BACKGROUND: Histone acetylation plays an important role in DNA replication and repair because replicating chromatin is subject to dynamic changes in its structures. However, its precise mechanism remains elusive. In this report, we describe roles of the NuA4 acetyltransferase and histone H4 acetylation in replication fork protection in the fission yeast Schizosaccharomyces pombe. RESULTS: Downregulation of NuA4 subunits renders cells highly sensitive to camptothecin, a compound that induces replication fork breakage. Defects in NuA4 function or mutations in histone H4 acetylation sites lead to impaired recovery of collapsed replication forks and elevated levels of Rad52 DNA repair foci, indicating the role of histone H4 acetylation in DNA replication and fork repair. We also show that Vid21 interacts with the Swi1-Swi3 replication fork protection complex and that Swi1 stabilizes Vid21 and promotes efficient histone H4 acetylation. Furthermore, our genetic analysis demonstrates that loss of Swi1 further sensitizes NuA4 and histone H4 mutant cells to replication fork breakage. CONCLUSION: Considering that Swi1 plays a critical role in replication fork protection, our results indicate that NuA4 and histone H4 acetylation promote repair of broken DNA replication forks.