Search

Exposure to ultraviolet radiation, which leads to the formation of mutagenic and cytotoxic DNA lesions such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4 PPs), can be potentially fatal. The way UVA forms DNA lesions and alters DNA topology and mechanics is still unclear, unlike the cases of UVC and UVB. Herein, Atomic Force Microscopy (AFM) and AFM-based Force Spectroscopy (AFS) have been employed to investigate the topological and mechanical properties of single DNA molecules, bare or E. coli cell-encapsulated, with or without UVA (solar or from UV lamp) treatment. It is observed that both the dsDNA transitions, i.e., 'B' to stretched 'S' conformation and melting transition, are lost in UVA dose-dependent manner. Presumably, this is due to formation of the CPDs and 6-4 lesions that form inter-strand cross-links, causing dsDNA strand separation difficult. Gradual reduction in DNA extension length upon prolonged treatment with UVA-only radiation or sunlight (where, 95 % of solar UV is UVA) also indicates formation of the inter-strand cross-links, since such cross-links can reduce DNA flexibility and increase DNA stiffness. Although these observations are common for both bare and cell-encapsulated DNA, the UVA dose at which the distinctive reversible B-S and melting transition faded away varied widely from 240 kJ/m 2 (bare DNA) to 900 kJ/m 2 (cellular DNA). The UV-induced DNA damage was also evident in observation of increased number of open circular and linearized topologies, as formed due to single-strand and double-strand breaks, respectively, at damage sites, upon combined action of the apurinic/apyrimidinic site-specific endonucleases IV and V. The extent of DNA damage was further quantified by enzyme-linked immunosorbent assay, which is found to be correlated to the single molecule information., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To describe the treatment outcomes of adalimumab in noninfectious pediatric uveitis., Methods: The electronic medical records of children with noninfectious uveitis were reviewed retrospectively. The visual improvement and ocular inflammation were assessed according to the Standardization of Uveitis Nomenclature criteria before and after treatment with adalimumab., Results: Twenty-nine eyes of 16 patients were included. The mean age of children was 9.4 ± 3.8 years. There were eight (50%) males and eight (50%) females. Juvenile idiopathic arthritis was the most common cause of uveitis in these children (N = 10, 62.5%), followed by Behçet's disease (N = 3, 18.75%) and Vogt-Koyanagi-Harada disease (N = 2, 12.5%). One child (6.25%) was diagnosed with Crohn's disease. Nine (56.3%) children were previously treated with methotrexate, one each with mycophenolate mofetil (MMF) (6.3%), azathioprine (6.3%), and tofacitinib (6.3%), and one child received MMF followed by azathioprine and cyclosporine before shifting to adalimumab. Three (18.8%) children did not receive prior immunosuppressive therapy. The average number of adalimumab injections given was 20.3 ± 12.0 at an interval of 2 weeks. The mean follow-up duration was 22.2 ± 16.6 months. Disease inactivity was achieved in 28 (96.6%) eyes at last visit ( P < 0.001). The best-corrected visual acuity (BCVA) improved from 0.48 ± 0.6 logMAR (logarithm of minimum of resolution) units at baseline to 0.20 ± 0.2 logMAR units at last visit ( P = 0.018). Disease remission was achieved in 23 (79.3%) eyes at the third month ( P = 0.001)., Conclusion: Adalimumab is effective in the treatment of pediatric noninfectious uveitis by achieving disease inactivity, reducing the recurrence rate and improving BCVA. The drug is safe and well tolerated., (Copyright © 2024 Indian Journal of Ophthalmology.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Solid pseudopapillary neoplasm (SPN) is an extremely rare, low-grade, malignant pancreatic tumour with an excellent prognosis. We describe a case of SPN causing obstructive jaundice in a young female, thus mimicking pancreatic adenocarcinoma clinically and radiologically., Case Presentation: A 32-year-old female presented with abdominal pain for 12 h, icterus, and an epigastric mass measuring 3 × 3 cm. Imaging studies revealed features of pancreatic neoplasm in the head of pancreas, possibly pancreatic adenocarcinoma. However, ultrasound-guided fine-needle aspiration cytology of the lesion revealed were indicative of SPN. The patient was managed by biliary decompression and underwent Whipple procedure for complete tumour resection. Histopathological analysis of the resected specimen confirmed the diagnosis of SPN., Discussion: SPN commonly presents in young females with abdominal pain, nausea, and vomiting. Our patient presented with jaundice, which is a rare finding even for pancreatic head tumours. Her clinical and radiological findings indicated pancreatic adenocarcinoma, since it commonly presents with painless jaundice, abdominal pain, and abdominal mass. Diagnostic confirmation is achieved by tissue biopsy - the presence of pseudopapillary patterns is a characteristic feature of SPN. Contrary to pancreatic adenocarcinoma, SPN has an excellent prognosis. Complete tumour resection is the mainstay of treatment for SPN, even in cases of local invasion or metastasis., Conclusion: SPN poses a diagnostic challenge due to its non-specific presentation. Clinicians should consider SPN as a differential in women presenting with abdominal mass and vague abdominal complaints. Complete surgical resection is the mainstay of treatment for SPN., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cytomegalovirus retinitis (CMVR) is a significant cause of blindness in patients with advanced acquired immunodeficiency syndrome (AIDS). There are no established guidelines for its treatment, resulting in varied antiviral approaches. We pooled data from 59 studies (4501 patients) to evaluate treatment variations and outcomes (CRD42022321088). Overall pooled estimates showed visual acuity improvement at 18 % (95 % CI: 7-41 %), inflammation resolution at 90 % (95 % CI: 81-95 %), retinal detachment at 11 % (95 % CI: 8-14 %), and recurrence at 19 % (95 % CI: 11-31 %). The main antiviral treatment approaches identified were: (1) intravenous antivirals alone in 33 studies, (2) intravitreal antivirals alone in 26 studies, (3) oral antivirals alone in 3 studies, and (4) a combination of systemic (oral or intravenous[IV]) and intravitreal antivirals in 7 studies, with varying schemes and durations. Ganciclovir was the predominant antiviral, with intravenous administration being the most reported (in 23 studies), followed by intravitreal administration (in 20 studies). While visual acuity improvement was comparable, inflammation resolution tended to be higher with intravitreal than with IV antivirals, though not statistically significant (88 %, 95 % CI: 69-96 % vs 75 %, 95 % CI: 35-94 %, p = 0.38). Retinitis progression rate for IV ganciclovir was lower than for those without ganciclovir. Inflammation recurrence was significantly lower in antiretroviral (ART)-treated compared to non-ART-treated HIV/AIDS patients (10 % (95 % CI: 4-20 %) vs 33 % (95 % CI: 19-50 %), p < 0.01). Neutropenia, particularly with ganciclovir, was the most reported adverse effect (up to 50 %)., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical features and treatment outcomes of patients with retinal vasoproliferative tumors. Methods: This retrospective case series comprised patients diagnosed with a retinal vasoproliferative tumor. Electronic medical records were reviewed, and patients' demographic details, clinical presentation, and treatment outcomes were analyzed. Results: Nineteen eyes of 19 patients with vasoproliferative tumors were included. The mean age (±SD) at presentation was 37.0 ± 16.95 years. No eye had bilateral tumors, and 1 eye had multiple tumors. Three eyes (15%) had primary tumors, while 16 (84%) had secondary tumors. Primary tumors mainly affected the inferotemporal quadrant (n = 3). Secondary tumors involved the inferior quadrant (n = 4), inferotemporal quadrant (n = 5), and inferonasal quadrant (n = 5). Secondary tumors were associated with Coats disease (n = 6), intermediate uveitis (n = 3), traumatic chorioretinopathy (n = 2), familial exudative vitreoretinopathy (n = 2), retinal vasculitis (n = 2), and retinal vascular occlusion (n = 1). Retinochoroidal features included intraretinal and subretinal exudates, subretinal fluid, intraretinal hemorrhaging, vitreous hemorrhaging, cystoid macular edema, vitritis, preretinal fibrosis, dilated feeding vessel, epiretinal membranes, and tractional retinal detachment. Treatment modalities included cryotherapy, laser photocoagulation, and local steroids. The mean follow-up was 25.3 months, during which 18 eyes had tumor regression and 1 had a worsening condition. Conclusions: Secondary vasoproliferative tumors were more frequently observed than primary tumors, often presenting as unilateral, unifocal tumors situated posterior to the equator in the inferior fundus. Conventional treatment approaches, such as cryotherapy and laser photocoagulation, were effective at tumor regression and often required multiple sessions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Dysregulation of the flow of information from genomic DNA to RNA to protein occurs within all cancer types. In this review, we described the current state of understanding of how RNA processing is dysregulated in cancer with a focus on mutations in the RNA splicing factor machinery that are highly prevalent in hematologic malignancies. We discuss the downstream effects of these mutations highlighting both individual genes as well as common pathways that they perturb. We highlight examples of how alterations in RNA processing have been harnessed for therapeutic intent as well as to promote the selective toxicity of cancer cells., (© 2024 Biswas et al.)

Purpose: To describe a cohort of patients with retinal vasoproliferative tumours (RVPT) seen in the uveitis clinic of a single tertiary eye care institute in India., Methods: Retrospective Chart Review., Results: In our study of 17 patients with 18 eyes affected by RVPTs, 94.1% showed unilateral involvement, one patient had bilateral RVPTs, and another had two RVPTs in the same eye. The mean age was 36.3 ± 15.1 years (range: 12-63 years), with a male majority (76.4%). The most common location was inferotemporal quadrant (44.4%). The most common associated uveitic condition was intermediate uveitis (50%). Patients were treated with oral corticosteroid (in 94.1%) and immunosuppressive (35.2%) in addition to transconjunctival cryotherapy (in 52.9%) or laser photocoagulation (in 41.1%). Regression of the RVPT was achieved in all cases except one. Visual acuity at time of detection of RVPT ranged from 6/6 to HM. No significant change was noted in the mean best corrected visual acuity pre and post treatment in the study group., Conclusion: RVPTs, rare peripheral retinal lesions often associated with intermediate uveitis, require early diagnosis with targeted therapy to prevent vision loss and achieve favorable long-term outcomes with rare recurrences.

Importance: This was the first study, to the authors' knowledge, to statistically evaluate the predictive accuracy of Collaborative Ocular Tuberculosis Study (COTS) calculator in guiding initiation of antitubercular therapy (ATT) in patients with clinically suspicious tubercular uveitis (TBU) in an international cohort., Objective: To evaluate the accuracy of a score of 4 or greater on the online COTS calculator in recommending ATT initiation., Design, Setting, and Participants: This study was an evaluation of a diagnostic test or technology. Data input required for the COTS calculator were extracted from the COTS-1 study dataset, which comprised retrospective, observational records of patients with TBU who were monitored for 12 months after treatment. Patients were recruited from international ophthalmic centers. In the absence of a traditional criterion standard, the 12-month treatment response to ATT was used to classify patients as disease positive or negative. The accuracy of clinicians at the ATT decision-making stage in the COTS-1 study was set against COTS calculator scores of 4 or greater. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), precision, recall, and F1 score, were computed. Data collected from January 2004 to December 2014 were analyzed., Exposures: COTS calculator to guide initiation of ATT in patients with TBU., Main Outcomes and Measures: Comparison of accuracy between clinician judgment and the COTS calculator, analyzed at varying scores and further stratified by tuberculosis endemicity., Results: Of the 492 participants (mean [SD] age, 42.3 [19.0] years; 233 male [47.3%]), application of the COTS calculator identified 225 (45.7%) with high or very high probability to start ATT (score = 4 or 5) and 111 (22.5%) with very high probability alone (score = 5). COTS-5 exhibited the highest specificity (88.7%; 95% CI, 81.4%-93.8%) compared with clinician judgment (29.6%; 95% CI, 21.4%-38.8%), and clinician judgment led in sensitivity (95.5%; 95% CI, 92.9%-97.4%) compared with COTS-5 (26%; 95% CI, 21.6%-30.7%). COTS-4 and COTS-5 balanced specificity (64.3%; 95% CI, 54.9%-73.1%) and sensitivity (48.8%; 95% CI, 43.7%-54%). PPV and sensitivity were consistently higher in the endemic group for all 3 tests., Conclusions and Relevance: Results of this diagnostic study suggest that the COTS calculator (score ≥4) was more specific than clinician judgment for ATT initiation. Although clinician judgment is a good first step to identify all potential true positives (with high sensitivity), a second consultation with COTS-5 (with high PPV) may lead to less false positives. This tool, apt for high-prevalence, low-resource settings, recommends ATT more selectively for genuine TBU cases. Large prospective studies are essential to explore potential improvements in the calculator's sensitivity.

Purpose: To evaluate the role of polymerase chain reaction (PCR) in detecting Mycobacterium tuberculosis (MTb) in granulomatous anterior uveitis and comparing the results with those of Mantoux test, QuantiFERON-TB Gold test, and High-Resolution Computed Tomography of Chest (HRCT-chest)., Methods: Data of 51 eyes of 38 patients with clinical features of granulomatous anterior uveitis undergoing anterior chamber fluid aspiration for PCR for MTb targeting IS6110 and MPB64 were studied., Results: Out of 38 patients, 25 (65.8%) were positive for MTb genome on PCR. 24 patients were tested for Mantoux, out of which 12 patients (50%) were positive and 12 patients (50%) were negative. 22 out of 38 patients had undergone QuantiFERON-TB Gold (QFT) test, out of which 10 (45.5%) were positive and 12 (54.5%) were negative. 36 out of 38 patients had undergone HRCT. Eight out of 38 (21.1%) patients had significant findings in HRCT-chest, as well as PCR positivity for MTb genome while 12 (31.6%) patients did not have any significant findings on HRCT-chest, but were positive for PCR., Conclusion: PCR for MTb is a valuable tool in the diagnosis of tubercular anterior uveitis. PCR can be positive even in cases of negative Mantoux test, QFT, and HRCT-chest in granulomatous anterior uveitis.

The white dot syndromes are a group of phenotypically similar disorders characterized by multiple lesions at the level of the outer retina, retinal pigment epithelium, and choroid. Common white dot syndromes whose imaging modalities have been described in this article are multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, multifocal choroiditis and panuveitis, punctate inner choroidopathy, serpiginous choroiditis, and birdshot chorioretinopathy. The various imaging modalities help us to better understand the pathophysiology of the various entities and help in diagnosing, monitoring, and prognosticating them. Optical coherence tomography angiography (OCTA) is a comparatively newer tool that helps us to visualize lesions in the choroid that correlate with indocyanine green angiography (ICGA) findings. Even though it is of limited value and cannot replace ICGA, it had gained considerable interest among ophthalmologists. Similarly, the noninvasive nature of modalities such as fundus autofluorescence and OCT makes them appealing and preferable over invasive techniques such as fundus fluorescein angiography and ICGA., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Oman Ophthalmic Society.)

Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. Using high-resolution fluorescent microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites, particularly more proximal regions, and increase this asymmetric localization following proteotoxic stress through microtubule-based transport from the soma. The most abundant chaperone mRNA in dendrites encodes the constitutive heat shock protein 70, HSPA8. Proteotoxic stress in cultured neurons, induced by inhibiting proteasome activity or inducing oxidative stress, enhanced transport of Hspa8 mRNAs to dendrites and the percentage of mRNAs engaged in translation on mono and polyribosomes. Knocking down the ALS-related protein Fused in Sarcoma (FUS) and a dominant mutation in the heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) impaired stress-mediated localization of Hspa8 mRNA to dendrites in cultured murine motor neurons and human iPSC-derived neurons, respectively, revealing the importance of these RNA-binding proteins in maintaining proteostasis. These results reveal the increased dendritic localization and translation of the constitutive HSP70 Hspa8 mRNA as a crucial neuronal stress response to uphold proteostasis and prevent neurodegeneration.

Abstract: An enucleated specimen of a silicone oil-filled globe, showing migration of oil globules into the intraretinal, choroidal, and ciliary body areas, surrounded by multinucleated giant cells suggestive of panuveitis on histopathological evaluation, was reported., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

In recent years, large-scale sequencing efforts have identified targetable driver mutations in haematopoietic stem cells. These efforts have led to the development and approval of nine novel agents for relapsed or refractory acute myelogenous leukaemia (R/R AML). However, despite an expansion in targeted therapies, achieving a durable remission in AML and high-risk myelodysplastic syndrome (HR-MDS) remains a significant challenge, and there is an urgent need for new effective treatments. Modulation of aberrant RNA splicing has emerged as a novel therapeutic approach in myeloid diseases. Aberrant splicing drives dysregulated gene expression that promotes tumourigenesis through increased proliferation and metastatic potential, immune evasion, decreased apoptosis, and chemotherapy resistance. Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Uveal effusion syndrome (UES) is an exudative detachment of ciliary body, retina and choroid. Various underlying causes leads to UES-like drugs (topiramate), inflammation and hypotony. Wnt gene involvement has never been associated with UES. We report a case of bilateral UES being misdiagnosed as Vogt-Koyanagi-Harada syndrome (VKH), with Wnt gene dysfunction as the underlying trigger., Observations: A 32-year-old male presented with diminution of vision in his left eye. He was found to have choroidal detachment with retinal detachment in his left eye. Choroidal detachment was noted in the right eye. Various ocular imaging including fundus fluorescein angiography and ocular coherence tomography was done. He was misdiagnosed as a case of VKH syndrome, for which he was treated with systemic immunomodulatory therapy. However, a subclinical response was made to revisit the diagnosis. Ultrasound biomicroscopy showed supraciliary effusion. Systemic and genetic evaluation led to the detection of Wnt10A pathway mutation., Conclusions: UES is an entity of diagnostic challenge. Careful and thorough systemic evaluation is required to clinch the diagnosis. We reported the first case of bilateral UES recalcitrant to corticosteroids, with Wnt10A gene mutation.

Intermediate uveitis is defined as inflammation of the vitreous and pars planitis. Etiology can be infectious, associated with a systemic disease, neoplastic or idiopathic. Pars planitis is the term used for idiopathic intermediate uveitis that presents with snowballs and snowbanks. While relatively rare, intermediate uveitis is present globally and typically affects adult females. Awareness of the presentation and a dilated fundus examination in patients presenting with floaters is essential to the diagnosis. PCR testing has enhanced the ability to diagnose infectious and neoplastic conditions that masquerade as intermediate uveitis. A structured review of systems and focused imaging, and laboratory testing will assist with early diagnosis and initiation of treatment.

Background: The purpose of this study was to report the incidence, time after inciting event, aetiology and risk after specific intraocular procedures and the visual outcomes associated with sympathetic ophthalmia (SO) occurrence., Methods: This study reports data from multiple retrospective cohorts: retrospective population-based data were extracted from the TRICARE service network (between 2017 and 2021) and retrospective case-based data from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database (cohorts from the UK, South India and North India)., Results: There were 159 patients with SO identified. The length of time from sensitising event to SO occurrence was a median of 151 days (range: 6-9100 days).In the TRICARE database, 2 patients developed SO after open globe trauma and primary repair (of 615 eyes, rate 0.33%; 95% CI 1.26% to 1.30%). None developed SO after vitrectomy (total of 23 903 events; 95% CI 0% to 0.012%). The combined North Indian and UK cohorts reported 78.6% (81 patients) after trauma, 18.45% (19 patients) after elective surgery.Visual outcomes were reported in the OASIS database for 98.01% of patients (155 of 157 patients). The median presenting and final best corrected visual acuity (BCVA) for the inciting eye were no perception of light, the median presenting and final BCVA for the sympathising eye were 0.65 and 0.3 logMAR, respectively., Conclusion: This study identified 159 cases of SO. With poor visual outcomes in the inciting eye, early diagnosis and management are crucial for optimising visual outcomes in the sympathising eye., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Gallbladder TB (GBTB) is a rare disease with a non-specific presentation, simulating cholecystitis and gallbladder malignancies. We describe a rare case of infiltrative GBTB with biliary strictures in a young female who was initially diagnosed with metastatic gallbladder carcinoma., Case Presentation: A 33-year-old female presented with recurrent episodes of obstructive jaundice, significant weight loss, fatigue, and oligomenorrhoea. Imaging studies revealed features of locally advanced gallbladder carcinoma with proximal and distal common bile duct strictures. However, biopsy of the liver tissue surrounding the gallbladder mass confirmed necrotizing granulomatous inflammation with similar findings from fine needle aspiration of the cervical lymph node. Along with the histopathological findings, radiological evidence of pulmonary tuberculosis confirmed the diagnosis of infiltrative GBTB. The patient was successfully managed with anti-tubercular drugs along with biliary decompression., Discussion: The rarity of GBTB is attributed to the high alkalinity of bile and bile acids, which afford protection against tubercle bacilli. Patients commonly present with abdominal pain, fever, abdominal lump, anorexia, and weight loss. Biliary strictures, though rare, have been described in GBTB and simulate cholangiocarcinoma. Due to the non-specific findings of pre-operative laboratory and radiological investigations, most patients are taken up for surgery and diagnosed with TB on post-operative histological analysis., Conclusion: Gallbladder TB is a rare disease which poses a diagnostic challenge because it lacks any pathognomonic features. A tissue diagnosis must be carried out before confirming gallbladder and biliary tract malignancies. Physicians in TB-endemic regions should possess a high index of suspicion for diagnosing GBTB., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The saphenous nerve is a predominantly sensory nerve. It is the longest nerve of the body which supplies the skin of the medial side of the leg and foot as far as the ball of the great toe. We present here an unusual motor branch of the saphenous nerve to the sartorius muscle., Method: Institutional guidelines for use of human cadaver were followed. Routine dissection of the lower limbs for undergraduate medical teaching was performed in a 67 years old female cadaver employing standard methods. Relevant gross features of the variations were photographed. H&E staining of relevant structure was done and photomicrographed., Results: The unusual motor branch to Sartorius was observed in the right thigh. The branch was given off in the lower third of the thigh after the saphenous nerve exited the adductor canal. The branch was distinctly seen entering the substance of the sartorius. The structure was confirmed to be a peripheral nerve by histological examination. The saphenous nerve then descended between the sartorius and gracilis tendons, pierced the fascia lata and became cutaneous., Conclusion: The motor branch to the sartorius muscle is a very rare branch whose knowledge is important for clinicians as it can get damaged during arthroscopy and other knee surgery or during adductor canal block., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment., Methods: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed., Results: Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans., Conclusions: The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.

FDA-approved antivirals against HCMV have several limitations, including only targeting the later stages of the viral replication cycle, adverse side effects, and the emergence of drug-resistant strains. Antivirals targeting host factors specifically activated within infected cells and necessary for viral replication could address the current drawbacks of anti-HCMV standard-of-care drugs. In this study, we found HCMV infection stimulated the activation of the stress response transcription factor heat shock transcription factor 1 (HSF1). HCMV entry into fibroblasts rapidly increased HSF1 activity and subsequent relocalization from the cytoplasm to the nucleus, which was maintained throughout viral replication and in contrast to the transient burst of activity induced by canonical heat shock. Prophylactic pharmacological inhibition or genetic depletion of HSF1 prior to HCMV infection attenuated the expression of all classes of viral genes, including immediate early (IE) genes, and virus production, suggesting HSF1 promotes the earliest stages of the viral replication cycle. Therapeutic treatment with SISU-102, an HSF1 inhibitor tool compound, after IE expression also reduced the levels of L proteins and progeny production, suggesting HSF1 regulates multiple steps along the HCMV replication cycle. Leveraging a newly developed human skin xenograft transplant murine model, we found prophylactic treatment with SISU-102 significantly attenuated viral replication in transplanted human skin xenografts as well as viral dissemination to distal sites. These data demonstrate HCMV infection rapidly activates and relocalizes HSF1 to the nucleus to promote viral replication, which can be exploited as a host-directed antiviral strategy., One Sentence Summary: Inhibiting of HSF1 as a host-directed antiviral therapy attenuates HCMV replication in vitro and in vivo.

Abstract: The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Objectives: This study aims to provide an in-depth exploration of everyday spiritual concerns of patients with advanced cancer seeking palliative care in Bangladesh, and assess their spiritual well-being (SWB)., Methods: This study was conducted among 163 patients with advanced cancer from three tertiary care hospitals in Bangladesh. It was divided into two parts: a quantitative segment that assessed the SWB of the participants using the EORTC QLQ SWB32, and a qualitative segment that explored their spiritual history., Result: Spirituality was commonly interpreted and understood synonymously with religion by all participants, and their sense of life's meaning centred on their families and friends. The lack of support from religious organisations led to feelings of isolation and disconnection from spiritual communities. Highest scores in SWB were observed in Relationships with God and Someone/Something Greater Scales. The lowest score was observed for Existential fulfilment. Patients expressed a desire for their palliative care team to address their spiritual concerns, regardless of their training in this area., Conclusion: Spirituality is a deeply personal aspect of the human experience. Understanding and respecting these beliefs can empower palliative care professionals to deliver culturally sensitive care to their patients, irrespective of their level of training., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Nitrite (NO 2 - ) serves as a pool of nitric oxide (NO) in biological systems under hypoxic conditions, and it is transformed to NO by nitrite reductase (NiR) enzyme in the presence of acid (H + ions). However, NO synthases (NOSs) generate NO via L-arginine oxidation in normoxic conditions. Previously, acid-induced NO 2 - reduction chemistry was modeled on mono-metallic 3d-metals, generating metal-nitrosyls or NO (g) with H 2 O or H 2 O 2 products. Herein, to understand the relative potency of a bimetallic system, we report the acid-induced reductive conversion of η 2 -bound NO 2 - to NO on Cu II -Co II centers of a hetero-bimetallic Cu II -nitrito-Co II complex, [(LN 8 H)Cu II -NO 2 - -Co II ] 3+ (Cu II -NO 2 - -Co II , 2) bearing an octadentate N 8 -cryptand ligand (LN 8 H). The Cu II -NO 2 - -Co II generates [Cu II (LN 8 H)Co II ] 4+ (1) upon reaction with one equiv. acid (HClO 4 , H + ions source) with NO (g) via a presumed transient nitrousacid (ONOH) intermediate species. Likewise, this NO 2 - reduction was found to form H 2 O, which is believed to be from the decomposition of H 2 O 2 , an intermediate species. In addition, complex 2, in the presence of more than one equiv. H + ions also showed the formation of NO (g) with H 2 O. Mechanistic investigations, using 15 N-labeled- 15 NO 2 - , 18 O-labeled- 18 O 14 N 16 O - and 2 H-labeled-DClO 4 (D + source), revealed that the N-atom and O-atom in the 14/15 NO and 14 N 18 O gases are derived from NO 2 - ligand and H-atom in H 2 O derived from H + -source, respectively., (© 2024 Wiley-VCH GmbH.)

Confocal laser endomicroscopy (CLE) is a novel endoscopic modality that provides real-time histological information via high-resolution magnified view of the mucosa. CLE has a higher sensitivity, specificity, and diagnostic accuracy in detecting atrophic gastritis as compared to chromoendoscopy and narrow-band imaging. It can even predict low-grade and high-grade intraepithelial neoplasia by analyzing gastric pit patterns. CLE may have some advantages over the standard biopsy protocol, such as higher diagnostic yield and fewer biopsy requirements. Its diagnostic accuracy in detecting superficial gastric cancer is higher than that of white-light endoscopy. Inherent limitations, such as a narrow field of vision, can be surpassed by technological advancements and integration with other detection methods. Artificial intelligence holds promise in automated analysis of histopathological images. Thus, CLE can be helpful in screening for early gastric cancer and may help reduce the risk of complications from repeated biopsies, such as mucosal damage, bleeding, and infection., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cell-cell junctions formed by the association of cell adhesion molecules facilitate physiological events necessary for growth and development of multicellular organisms. Among them, cadherins and nectins organize and assemble to form adherens junction, which thereby mechanically couples interacting cells. A detailed understanding of the crosstalk involving these cell adhesion molecules is fundamental to the study of the various developmental processes. Although, cadherins and nectins can recruit each other in the adherens junction through an interplay of cytoplasmic adaptor molecules, here, we report a direct interaction between N-terminal extracellular domains of E-cadherin and nectin-4 as demonstrated by surface plasmon resonance (SPR) and Atomic Force Microscopy (AFM)-based single molecule force spectroscopy (SMFS). Kinetic studies using SPR demonstrate the binding between the ectodomains of E-cadherin and nectin-4 with a K D of 3.7 ± 0.7 µM and K D of 5.4 ± 0.2 µM (reciprocal experiment). AFM-based SMFS experiments also support interaction between the ectodomains of E-cadherin and nectin-4 with the k off value of 31.48 ± 1.53 s -1 and the lifetime of the complex of 0.036 ± 0.0026 s. We thus propose a cell adhesion mechanism mediated by E-cadherin and nectin-4, which can have functional significance in early embryogenesis as evident from the expression pattern of both the proteins during early development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Myelinating oligodendrocytes arise from the stepwise differentiation of oligodendrocyte progenitor cells (OPCs). Approximately 5% of all adult brain cells are OPCs. Why would a mature brain need such a large number of OPCs? New myelination is possibly required for higher-order functions such as cognition and learning. Additionally, this pool of OPCs represents a source of new oligodendrocytes to replace those lost during injury, inflammation, or in diseases such as multiple sclerosis (MS). How OPCs are instructed to differentiate into oligodendrocytes is poorly understood, and for reasons presently unclear, resident pools of OPCs are progressively less utilized in MS. The complement component 1, q subcomponent-like (C1QL) protein family has been studied for their functions at neuron-neuron synapses, but we show that OPCs express C1ql1. We created OPC-specific conditional knockout mice and show that C1QL1 deficiency reduces the differentiation of OPCs into oligodendrocytes and reduces myelin production during both development and recovery from cuprizone-induced demyelination. In vivo over-expression of C1QL1 causes the opposite phenotype: increased oligodendrocyte density and myelination during recovery from demyelination. We further used primary cultured OPCs to show that C1QL1 levels can bidirectionally regulate the extent of OPC differentiation in vitro. Our results suggest that C1QL1 may initiate a previously unrecognized signaling pathway to promote differentiation of OPCs into oligodendrocytes. This study has relevance for possible novel therapies for demyelinating diseases and may illuminate a previously undescribed mechanism to regulate the function of myelination in cognition and learning., (© 2024 Federation of European Biochemical Societies.)

Necrotizing scleritis is the most destructive and vision-threatening form of scleritis. Necrotizing scleritis can occur in systemic autoimmune disorders and systemic vasculitis, as well as following microbial infection. Rheumatoid arthritis and granulomatosis with polyangiitis remain the commonest identifiable systemic diseases associated with necrotising scleritis. Pseudomonas species is the most common organism causing infectious necrotizing scleritis, with surgery the most common risk factor. Necrotizing scleritis has the highest rates of complications and is more prone to secondary glaucoma and cataract than other phenotypes of scleritis. The differentiation between non-infectious and infectious necrotizing scleritis is not always easy but is critical in the management of necrotizing scleritis. Non-infectious necrotizing scleritis requires aggressive treatment with combination immunosuppressive therapy. Infectious scleritis is often recalcitrant and difficult to control, requiring long-term antimicrobial therapy and surgical debridement with drainage and patch grafting due to deep-seated infection and the avascularity of the sclera.

Establishing a nonproductive, quiescent infection within monocytes is essential for the spread of human cytomegalovirus (HCMV). We investigated the mechanisms through which HCMV establishes a quiescent infection in monocytes. US28 is a virally encoded G protein-coupled receptor (GPCR) that is essential for silent infections within cells of the myeloid lineage. We found that preformed US28 was rapidly delivered to monocytes by HCMV viral particles, whereas the de novo synthesis of US28 was delayed for several days. A recombinant mutant virus lacking US28 (US28Δ) was unable to establish a quiescent infection, resulting in a fully productive lytic infection able to produce progeny virus. Infection with US28Δ HCMV resulted in the phosphorylation of the serine and threonine kinase Akt at Ser 473 and Thr 308 , in contrast with the phosphorylation of Akt only at Ser 473 after WT viral infection. Inhibiting the dual phosphorylation of Akt prevented the lytic replication of US28Δ, and ectopic expression of a constitutively phosphorylated Akt variant triggered lytic replication of wild-type HCMV. Mechanistically, we found that US28 was necessary and sufficient to attenuate epidermal growth factor receptor (EGFR) signaling induced during the entry of WT virus, which led to the site-specific phosphorylation of Akt at Ser 473 . Thus, particle-delivered US28 fine-tunes Akt activity by limiting HCMV-induced EGFR activation during viral entry, enabling quiescent infection in monocytes.

Purpose: To study and compare the clinical characteristics and outcome of ocular syphilis between HIV positive and HIV negative patients., Methods: Retrospective hospital-based case series from a tertiary eye care hospital in India. Patients with uveitis and positive syphilis serology were included. Demographics, clinical features, investigations, imaging and treatment modalities were noted., Results: Hundred and five (105) eyes of 66 patients were analyzed. Males were predominantly affected ( n  = 57/66, 86.4%). Secondary syphilis was the most common stage of presentation ( n  = 48/66, 72.7%). Two groups were identified: HIV positive (HIVP) patients ( n  = 39/66, 59%) and HIV negative (HIVN) patients ( n  = 27/66, 41%). 12/39 (30.8%) patients were newly diagnosed with HIV at the time of ocular presentation. Panuveitis was the most common presenting feature in both groups ( n  = 66/105 eyes, 62.8%). Diffuse necrotizing retinitis was more common in HIV patients (HIVP - 15 Vs HIVN - 5 eyes). Ocular co-infections were more common in HIV patients, ocular tuberculosis, the commonest in both groups. Intravenous penicillin and titrated dose of systemic steroids were the mainstay of treatment. Improvement in mean logMAR was noted from 1.415 to 0.828 with p -value < 0.001. At final follow-up, 71.8% patients showed visual improvement. Complete resolution of ocular inflammation was noted in 95.5% patients., Conclusion: Ocular syphilis poses a diagnostic challenge considering the varied presentations and clinical course both in immunocompromised and immunocompetent groups. Clinical presentations are not always classical. High index of suspicion with supportive laboratory investigations and with characteristic OCT features helps diagnosis. All uveitis patients, especially with those suspected with infectious etiology, need to be tested for syphilis serology to prevent vision loss in this resurgent disease.

Purpose: To report the treatment response of a case of tubercular choroidal granuloma and subretinal abscess with intravitreal anti-vascular endothelial growth factor (anti-VEGF) and moxifloxacin., Method: Retrospective interventional case report., Results: A 34-year-old man presented with bilateral choroidal granuloma and subretinal abscess in one eye. He was a known case of spinal tuberculosis and was on anti-tubercular therapy. Patient was successfully treated with intravitreal injection of anti-VEGF and moxifloxacin., Conclusion: Intravitreal anti-VEGF and moxifloxacin combination may be beneficial in tubercular choroidal granuloma and subretinal abscess.

Purpose: To report the use of tofacitinib in ten patients with scleritis where the traditional immunomodulation was not successful or could not be used., Method: A retrospective chart review., Result: Tofacitinib was successful in the treatment of scleritis in patients either recalcitrant to or intolerant to conventional therapy in 9 out of 10 cases reported here. Two patients had developed reactivation of herpetic infection after 1 month of starting tofacitinib. The duration from diagnosis of scleritis to the institution of tofacitinib therapy varied from 1 month to 60 months. Duration of follow-up varies from 2 months to 11 months., Conclusion: Tofacitinib can be used as an important future option for managing recurrent and recalcitrant cases of scleritis.

Purpose: To describe a rare case of bilateral frosted branch angiitis with macular exudates in a 5-year-old boy presumed to be secondary to an Epstein-Barr virus (EBV) infection., Observations: A 5-year-old boy presented with acute onset blurring of vision in both eyes, the best corrected visual acuity was 3/60 in both eyes. The anterior segment was unremarkable, fundus showed the presence of perivascular sheathing involving the macular vessels, exudates, and subretinal fluid at the fovea (OU). Serology was positive for EBV. Swept-source optical coherence tomography angiography showed areas of flow void in the superficial and deep capillary plexus that disappeared with reduction of inflammation following treatment with intravenous, oral and topical steroids, and oral valacyclovir., Conclusions: Frosted branch angiitis can present following an EBV infection.

The perception of social support among patients with advanced diseases is influenced by various factors. The socio-cultural context of Bangladesh significantly shapes the experience of patients with advanced cancer and their perception of social support. This study's aim was to assess the perceived social support by these patients and investigate the factors that shape their perception. This cross-sectional study was conducted among 115 advanced cancer patients admitted to the palliative medicine department of a tertiary care hospital in Bangladesh. Perceived social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). Perceived social support was moderate to high for most (74.7%) of the participants. The majority (97.4%) perceived moderate to high level of support from their families. The lowest level of support was perceived from friends (53%). Factors such as economic status, family size, companionship of children, and emotional support from spouses influenced the level of perceived social support. Social support is one of the important aspects of palliative care. Identifying the factors influencing the perception of social support among cancer patients is essential for palliative care professionals to effectively address their care needs.

Purpose: To evaluate the spectrum of uveitis occurring after 60 years of age in elderly patients who presented to a tertiary care eye center in India., Methods: Retrospective study of patients who visited a tertiary eye care institute between January 2010 and July 2020., Result: Eighty-seven patients developed uveitis after 60 years, with only 44.8% having sufficient follow-up documentation and were included in the final analysis. The median age of these patients was 64 (IQR: 62-70) years, and 69% of them were male. Among the identifiable causes of uveitis, infectious uveitis (36%) was the most common and noninfectious uveitis was noted in 23% of patients. The most common subtype of uveitis was anterior uveitis (52%), followed by intermediate uveitis (32%), panuveitis (11%), and posterior uveitis (7%). Tuberculosis (28%) was the most common cause in our cohort, followed by HLA B27 (10%), sarcoid (8%), and Vogt-Koyanagi-Harada disease (5%). In 41% of patients, a definitive diagnosis of uveitis could not be achieved, and the anterior uveitis group had the highest number of undifferentiated uveitis cases. There were no undifferentiated cases of uveitis in the posterior and panuveitis category. The median follow-up period of these patients was 52 (15-91) months and 66% of eyes had recurrence. A statistically significant improvement in vision was seen in anterior uveitis and panuveitis groups, whereas the median visual acuity of the intermediate uveitis group remained stable throughout the follow-up period., Conclusion: Uveitis in the elderly can have a higher recurrence rate; however, the lack of follow-up in these groups of patients is a major challenge., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: To report the clinical pattern of surgically induced necrotizing scleritis (SINS) in a tertiary eye care center in Southern India., Methods: Retrospective analysis of all SINS cases visiting the uveitis clinic of a tertiary eye institute between January 2009 and April 2019., Results: In total, 15 patients with a median age of 65 (IQR: 52-70) years were included in the study. Male (53%) predominance was noted, and SINS was unilateral (100%) in all cases. Most (87%) of the patients developed SINS after a single surgical procedure, with a median onset period of 251 (IQR: 127-1095) days. None of these patients had any evidence of systemic association. Ocular hypertension (n = 3, 20%), and cataract (n = 5, 33%) were the most common complications. When compared with a cohort of patients with idiopathic necrotizing scleritis, the index study did not find any statistically significant difference between SINS and idiopathic scleritis., Conclusion: SINS is idiopathic necrotizing scleritis rather than an independent entity of scleritis., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: To report a case of endogenous endophthalmitis caused by Sphingomonas paucimobilis in a young male., Materials and Methods: A retrospective case report., Results: A 25-year-old male presented with reduced vision in the right eye and recurrent past episodes of hypopyon uveitis. The right eye had vision of counting fingers close to the face with cells, flare, and hypopyon in the anterior chamber with vitritis and exudates in the fundus. Blood investigations for tuberculosis, syphilis, toxoplasma, sarcoidosis, RA, ANA, HLA B27, and HLA B29 were negative. Anterior chamber tap investigations for herpes simplex viruses, varicella-zoster virus, cytomegalovirus, and toxoplasma, as well as Mycobacterium tuberculosis, yielded negative results. Ultrasound B-scan revealed a moderate number of low-reflective dot echoes in the vitreous, along with a few membranous echoes suggestive of vitritis. Blood culture and urine culture were negative. Since there was progressive deterioration, diagnostic and therapeutic vitrectomy was done with intravitreal antibiotics. The culture of the vitreous sample grew Sphingomonas paucimobilis. In the post-operative period, the patient developed retinal detachment, and re-surgery was done with a lensectomy, and the vision improved to 6/18 with contact lenses in the follow-up., Conclusion: This case report describes the distinct occurrence of endogenous endophthalmitis in an immunocompetent young male, which was previously reported only in peripartum cases. The clinical course is characterized by masquerading symptoms and recurrent episodes, despite the organism being of low virulence.

Uveitis and its complications are more common in the developing world, in which the condition occurs in up to 714 per 100,000 in the population and accounts for up to 25% of all blindness. In India, the ophthalmic sub speciality of uveitis greatly evolved in the last four decades. In the early decades most of the studies were epidemiological studies. In recent years, more research has been published due to tremendous advancements in clinical diagnosis, laboratory investigations and ancillary test and treatment modalities. In this review article, we did a medline search with key words 'uveitis' and 'India', and selectively incorporated articles showing the evolution of this sub-speciality in India., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)