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Describes a physical/organic chemistry experiment on conductance behavior of hydrogen-bonded species of six salts of easily accessible, nitrogen-containing bases and halogenoacetic acids. The bases and acids used are much cheaper and have comparatively less unpleasant odors than the pyrim puridines and trifluoroacetic acid used in previously reported experiments. (JN)

PurposeTo study the outcome of therapy for acute endothelial graft rejection with an intravenous (i.v.) pulse of dexamethasone vs methylprednisolone, in addition to topical corticosteroids.MethodsRecords of 98 eyes of 99 patients treated for endothelial graft rejection with a single i.v. pulse of dexamethasone or methylprednisolone in addition to topical steroids, between January 1999 and June 2004, were retrospectively reviewed. Baseline characteristics such as surgery-rejection interval, time taken to consult after onset of symptoms, history of failed grafts, extent of stromal vascularization, best-corrected visual acuity (BCVA) and corneal thickness at the time of presentation were noted. Main outcome measures following treatment for rejection included improvement in BCVA, change in corneal thickness, and reversal of graft rejection.ResultsFifty-one patients were treated with i.v. methylprednisolone and 47 with i.v. dexamethasone, in addition to topical steroids. Both groups were found to be comparable with respect to baseline parameters, that is, time taken to present, history of failed grafts, extent of stromal vascularization, BCVA, and graft thickness. Graft rejection could be successfully reversed in 72.3% cases in the dexamethasone group and 49% in the methylprednisolone group (P=0.018). A significant improvement in visual acuity was recorded following treatment in both groups, with a better outcome in the dexamethasone group (P=0.012). Post-treatment pachymetry values were lower than pretreatment values in both groups, with significantly lower final pachymetry in the dexamethasone group (P=0.017). No adverse effects were observed.ConclusionI.v. pulse therapy with dexamethasone may be used as an effective alternative to methylprednisolone in reversing acute endothelial graft rejection.Eye (2009) 23, 635–639; doi:10.1038/eye.2008.25; published online 22 February 2008 [ABSTRACT FROM AUTHOR]

The article presents a case report which examines necrotizing scleritis and peripheral ulcerative keratitis in Sweet's syndrome that was found culture-positive for Mycobacterium tuberculosis. The characteristics of this syndrome include an abrupt onset of fever, pseudo-vesicular, papulo-nodular plaque lesions, a neutrophilic dermal infiltrate without vasculitis, and a response to systemic corticosteroid. The case report, which involves a 47-year-old man from New Delhi, discusses sight-threatening complications found during examination.

Introduces a processing technique that involves electrophoretic deposition (EPD) to produce reinforced borosilicate-glass-matrix composites with nickel interface. Deposition of particles onto unidirectionally aligned fibers; Preparation and characterization of borosilicate sol suitable for EPD; Parameters for EPD processing; Prevention of crack growth; Benefits of the technique.

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The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2-neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds to the back left shoulder of the SARS-CoV-2 spike protein receptor binding domain and prevents interaction with the human angiotensin-converting enzyme 2 receptor. AZD3152 potently neutralized a broad panel of pseudovirus variants, including the currently dominant Omicron variant JN.1 but has reduced potency against XBB subvariants containing F456L. In vitro studies confirmed F456L resistance and additionally identified T415I and K458E as escape mutations. In a Syrian hamster challenge model, prophylactic administration of AZD3152 protected hamsters from weight loss and inflammation-related lung pathologies and reduced lung viral load. In the phase 1 sentinel safety cohort of the ongoing SUPERNOVA study (ClinicalTrials.gov: NCT05648110), a single 600-mg intramuscular injection of AZD5156 (containing 300 mg each of AZD3152 and cilgavimab) was well tolerated in adults through day 91. Observed serum concentrations of AZD3152 through day 91 were similar to those observed with cilgavimab and consistent with predictions for AZD7442, a SARS-CoV-2-neutralizing antibody combination of cilgavimab and tixagevimab, in a population pharmacokinetic model. On the basis of its pharmacokinetic characteristics, AZD3152 is predicted to provide durable protection against symptomatic coronavirus disease 2019 caused by susceptible SARS-CoV-2 variants, such as JN.1, in humans.

Purpose: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia., Design: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter., Participants: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries., Interventions: Chemotherapy, radiotherapy, enucleation, and orbital exenteration., Main Outcome Measures: Enucleation and death., Results: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively., Conclusions: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203)., Competing Interests: Declaration of interests U.S. and O.T. are management board members and employees at BioNTech SE. R.B.G. serves on the Board of Directors for Alkermes PLC, Infinity Pharmaceuticals, and Zai Laboratory; serves on the Scientific Advisory Board for Leap Therapeutics; is a consultant for Third Rock Ventures; and is a stockholder and employee of BioNTech US. B.C. and S.K. are employees of Bioqual, Inc. S.S. is an employee of Southern Research. A.Z., C.L.D., N.D.S., M.M., Y.J.L., G.M.P., A.D., R.S.V., K.S., A.G., C.L., D.A.R., H.D., A.C.W., T.A.A., F.M., A.B.V., L.M.S., R.v.d.M., J.R.S., and A.P. are current/past employees of BioNTech SE/BioNTech US, are stockholders, and/or are inventors on patents and patent applications related to RNA vaccines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 10 5 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90 % along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Subeena Sood, Majed M. Matar, Jessica Kim, Meredyth Kinsella, Kempaiah Rayavara, Olivia Signer, John Henderson, Joseph Rogers, Austin Arnold, Jennifer S. Rice, Alanna M. Smith, Daishui Sui, Jeff Sparks, Corinne Le Goff, Jean D. Boyer and Khursheed Anwer report other support from Imunon Corporation during the conduct of the study. No disclosures were reported by the other authors.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed., Purpose: The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas., Synopsis: The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration., Highlights: In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque., Video Link: https://youtu.be/YMIg3rYyp2o., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background: Retinoblastoma (RB) is initiated by mutation in both alleles of RB1 gene. However, few cases may occur even in the absence of RB1 mutation suggesting the role of genes other than RB1 ., Methodology: The current study was planned to utilize targeted exome sequencing in Indian RB patients affected with unilateral non-familial RB. 75 unilateral RB patients below 5 years of age were enrolled. Genomic DNA was extracted from blood and tumor tissue. From peripheral blood DNA, all coding and exon/intron regions were amplified using PCR and direct sequencing. Cases which did not harbor pathogenic variants in peripheral blood DNA were further screened for mutations in their tumor tissue DNA using targeted exome sequencing. Three pathogenicity prediction tools (Mutation Taster, SIFT, and PolyPhen-2) were used to determine the pathogenicity of non-synonymous variations. An in-house bioinformatics pipeline was devised for the mutation screening by targeted exome sequencing. Protein modeling studies were also done to predict the effect of the mutations on the protein structure and function., Results: Using the mentioned approach, we found two novel variants (g.69673&#95;69674insT and g.48373314C>A) in RB1 gene in peripheral blood DNA. We also found novel variants in eight genes ( RB1 , ACAD11 , GPR151 , KCNA1 , OTOR , SOX30 , ARL11 , and MYCT1 ) that may be associated with RB pathogenesis., Conclusion: The present study expands our current knowledge regarding the genomic landscape of RB and also highlights the importance of NGS technologies to detect genes and novel variants that may play an important role in cancer initiation, progression, and prognosis.

Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in Caenorhabditis elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the dosage compensation complex which binds to both hermaphrodite X chromosomes and reduces transcriptional output by half. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probes and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3, as well as mutants for the piRNA Argonaute prg-1, exhibit derepression of xol-1 transcripts, they also affect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and found that hrde-1 and nrde-3 contribute to healthy dosage compensation both upstream and downstream of xol-1., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Breast cancer is the most common cancer among women in India causing increased mortality. Lack of awareness leads to detection of breast cancer in advanced stages and is difficult to cure then., Objective: A systematic review was conducted to evaluate the knowledge, attitude, and practice of breast cancer and its screening among women in India., Methodology: Literature search was done on electronic databases including PubMed and Google Scholar. Specific keywords related to breast cancer were used such as breast cancer or breast carcinoma AND awareness or knowledge or attitude or education or practice AND women or females AND India. Searches were limited to articles published in English language in the last 10 years., Results: Fifteen studies were selected with a total of 7545 women between the age of 14 and 75 years. Study population varied from health-care professionals, rural and urban women to general population. Majority of the women were married with illiteracy levels ranging from 5.6% to 42.8%. The knowledge of breast cancer was seen to be 62.99%. Knowledge and attitude toward breast cancer screening were 78.67% and 71.10%, respectively. Most reviewed studies showed a significant association of the knowledge of breast cancer with the education level, marital status, and age of study participants., Conclusion: Majority of the population knew about breast cancer and had low percentage for practice of screening methods. Programs on information about breast cancer are required. Women from all populations need to be motivated for positive change toward proper screening, early detection, and treatment of breast cancer., Competing Interests: None

Purpose: To report the association of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) mutations with bilateral primary congenital glaucoma (PCG) in monozygotic twins and with nondominant juvenile-onset primary open-angle glaucoma (JOAG)., Methods: We utilized family-based whole-exome sequencing to detect disease-causing mutations in a pair of monozygotic twins with de-novo PCG and compared its existence in 50 nonfamilial cases of JOAG and 30 healthy controls. To validate the identified mutations, direct Sanger sequencing was performed. For further evaluation of gene expression in the ocular tissues, we performed whole-mount in situ hybridization in zebrafish embryos., Results: We identified a novel missense mutation (c.1925A>G, p.Tyr642Cys) in the PLOD2 gene in the monozygotic twin pair with PCG and another missense mutation (c.1880G>A, p.Arg627Gln) in one JOAG patient. Both mutations identified were heterozygous. Neither the parents of the twins nor the parents of the JOAG patient harbored the mutation and it was probably a de-novo change. The zebrafish in situ hybridization revealed expression of the PLOD2 gene during embryogenesis of the eye., Conclusion: We observed an association of PLOD2 mutations with PCG and with nonfamilial JOAG. This new gene needs to be further investigated for its role in pathways associated with glaucoma pathogenesis., Competing Interests: None